Neoplasms, BreastPhase 2INDUCTNCT01220128
Evaluation of an Anti-cancer Immunotherapy Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer
A Phase 2 study testing GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A, Aromatase inhibitor and 5-Fluorouracil in people with Neoplasms, Breast, run by GlaxoSmithKline at 36 sites in 7 countries.
Trial summary
The purpose of this study is to evaluate the safety, immunogenicity and clinical activity of a new WT1 anti-cancer immunotherapy in patients with WT1-positive Stage II or III breast cancer. The treatment will be given before surgery in combination with standard therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Breast
- What is being tested?
- GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A, Aromatase inhibitor and 5-Fluorouracil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 36 sitesin 7 countries
- Study dates
- 11 Apr 2011to 14 Nov 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient is ≥ 18 years of age at the time the informed consent to screening has been obtained.
- The patient has proven T1 with lymph node involvement or T2-T4c, any N, M0 primary invasive breast cancer, histologically confirmed by core needle biopsy.
- Isolated supraclavicular lymph node involvement is allowed.
- The patient's tumor shows WT1 antigen expression.
- The patient has one of the following histologically confirmed breast cancer subtypes:
- Estrogen receptor and/or progesterone positive tumor.
Show all 25Show fewer
- Human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer.
- HER2-negative breast cancer.
- Eastern Cooperative Oncology Group (performance status of 0 or 1 at the time of study treatment allocation.
- Baseline left ventricular ejection fraction of ≥ 50% as measured within six weeks prior to study treatment allocation by echocardiography or multi-gated acquisition(MUGA)scan.
- The patient shows normal organ function according to the following parameters(as measured within six weeks prior to treatment allocation)::
- Hemoglobin: Within normal range according to institutional standards.
- Absolute leukocyte count: Within normal range according to institutional standards.
- Absolute lymphocyte count: Within normal range according to institutional standards.
- Platelet count: Within normal range according to institutional standards
- Alanine aminotransferase: ≤ 2.5 x Upper Limit of Normal (ULN)
- Aspartate aminotransferase: ≤ 2.5 x ULN
- Total bilirubin: ≤ 1.5 x ULN. In the case of known Gilbert's syndrome ≤ 2 x ULN
- Serum creatinine: 1.5 x ULN
- Calculated creatinine clearance: > 50 mL/min
- A female patient of childbearing potential may be enrolled in the study, if the patient:
- has practiced adequate contraception for 30 days prior to study product administration, and
- has a negative pregnancy test within one week prior to treatment allocation and
- has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the study product administration series.In view of the investigator, the patient can and will comply with the requirements of the protocol.
- Written informed consent has been obtained from the patient prior to performance of any study specific procedure.
Who cannot join
- The patient has inflammatory breast cancer, which is defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion.
- Diagnosis established by incisional biopsy.
- Prior and concomitant neoadjuvant anti-breast-cancer treatments such as chemotherapy, immunotherapy / biological response modifiers, endocrine therapy, and radiotherapy, unless authorized specifically by the protocol.
- The patient is known to be human immunodeficiency virus -positive.
- The patient has symptomatic autoimmune disease such as, but not limited to multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded.
- The patient is known to have difficult-to-control hypertension, coronary artery disease, arrhythmia requiring treatment, clinically significant valvular disease, cardiomegaly on chest X-ray, ventricular hypertrophy on electrocardiogram or previous myocardial infarction or congestive heart failure.
Show all 13Show fewer
- The patient has a history of allergic reactions likely to be exacerbated by any component of the investigational product used in the study.
- The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
- The patient has (or has had) previous or concomitant malignancies at other sites, except effectively treated malignancy that is considered by the investigator highly likely to have been cured.
- The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the study procedures.
- The patient has received any investigational or non-registered product within 30 days preceding the first dose of study products or planned use during the study period.
- The patient requires concomitant treatment with any immunosuppressive agents or with systemic corticosteroids prescribed for chronic treatment.
- The patient has a significant disorder of coagulation or receives treatment with warfarin derivatives or heparin. Patients receiving individual doses of low molecular weight heparin outside of 24 hours prior to WT1-A10 + AS15 ASCI/placebo administration are eligible. Patients receiving prophylactic antiplatelet medications e.g. low-dose aspirin, and without a clinically-apparent bleeding tendency are eligible.
Trial locations and contacts
36 sites in 7 countries.
36 sites in 7 countries
United States8 sites
GSK Investigational Site
Amarillo, Texas, 79106
GSK Investigational Site
Ann Arbor, Michigan, 48109-5848
GSK Investigational Site
Bend, Oregon, 97701
GSK Investigational Site
Boston, Massachusetts, 02114
GSK Investigational Site
Memphis, Tennessee, 38120
GSK Investigational Site
Newark, Delaware, 19713
GSK Investigational Site
Plantation, Florida, 33324
GSK Investigational Site
Spokane, Washington, 99208
Germany8 sites
GSK Investigational Site
Chemnitz, Saxony, 09116
GSK Investigational Site
Dortmund, North Rhine-Westphalia, 44137
GSK Investigational Site
Erlangen, Bavaria, 91054
GSK Investigational Site
Essen, North Rhine-Westphalia, 45136
GSK Investigational Site
Frankfurt am Main, Hesse, 60590
GSK Investigational Site
Kiel, Schleswig-Holstein, 24105
GSK Investigational Site
Rostock, Mecklenburg-Vorpommern, 18059
GSK Investigational Site
Tübingen, Baden-Wurttemberg, 72076
Italy7 sites
GSK Investigational Site
Aviano (PN), Friuli Venezia Giulia, 33081
GSK Investigational Site
Genoa, Liguria, 16132
GSK Investigational Site
Milan, Lombardy, 20141
GSK Investigational Site
Naples, Campania, 80131
GSK Investigational Site
Pavia, Lombardy, 27100
GSK Investigational Site
Trento, Trentino-Alto Adige, 38100
GSK Investigational Site
Turin, Piedmont, 10126
United Kingdom5 sites
GSK Investigational Site
Belfast, BT9 7AB
GSK Investigational Site
Bournemouth, BH7 7DW
GSK Investigational Site
Derby, DE22 3DT
GSK Investigational Site
Edinburgh, EH4 2XU
GSK Investigational Site
Nottingham, NG5 1PB
Belgium3 sites
GSK Investigational Site
Brussels, 1200
GSK Investigational Site
Leuven, 3000
GSK Investigational Site
Namur, 5000
Russia3 sites
GSK Investigational Site
Ryazan, 390011
GSK Investigational Site
Saint Petersburg, 197022
GSK Investigational Site
Saint Petersburg, 197758
France2 sites
GSK Investigational Site
Lyon, 69373
GSK Investigational Site
Saint-Herblain, 44805
About this study
Official title: Study of GSK2302024A Antigen-Specific Cancer Immunotherapeutic Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer
The purpose of this study is to evaluate the safety, immunogenicity and clinical activity of a new WT1 anti-cancer immunotherapy in patients with WT1-positive Stage II or III breast cancer. The treatment will be given before surgery in combination with standard therapy.
Read the detailed description
The study will be conducted in two consecutive segments (Phase I and Phase II), each with specific objectives. Active follow-up will be for three years.
Patients in this study will be allocated to cohorts as below. Cohort A will include postmenopausal patients with hormone receptor-positive breast cancer who receive aromatase inhibitor (AI) as neoadjuvant therapy concurrently with administration of 6 or 8 doses of WT1 anti-cancer immunotherapy (WT1 ASCI)/placebo starting on Day 0. AI treatment will be administered daily for duration of either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo).
Cohort B will include breast cancer patients who will receive neoadjuvant chemotherapy concurrently with administration of WT1 ASCI/placebo starting on Day 0. Neoadjuvant chemotherapy in Cohort B will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly or 12-weekly taxane administrations without trastuzumab.
Cohort C will include patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who will receive neoadjuvant trastuzumab (Herceptin) therapy combined with chemotherapy concurrently with administration of WT1 ASCI/placebo starting on Day 0. Neoadjuvant chemotherapy in Cohort C will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly or 12-weekly taxane administrations with trastuzumab.
Cohorts D and E will include patients with hormone receptor-positive and HER2 non-overexpressing breast cancer who will receive neoadjuvant chemotherapy. For patients in these Cohorts D and E, WT1 ASCI/placebo (placebo applicable only for Cohort E patients) will be administered on Day 14 of each three-weekly cycle of chemotherapy. Neoadjuvant chemotherapy in Cohorts D and E will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly taxane administrations without trastuzumab. Enrolment in Cohort E will be conditional on the absence of a safety signal and on the adequate induction of an immune response by the WT1 ASCI in Cohort D (defined as >= 40% response rate based on post-Dose 4 anti-WT1 antibody responses in at least six patients). If this criterion is met, 60 patients (40 receiving WT1 ASCI and 20 placebo) with identical eligibility criteria will be enrolled into Cohort E. In case no adequate safety and/or immunogenicity will be obtained in Cohort D, recruitment in Cohort E will not be initiated.
The protocol has been updated following Protocol Amendment 4, April 2013, leading to the update of the study design.
- Conditions
- Neoplasms, Breast
- Being tested
- GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A, Placebo, Aromatase inhibitor, 5-Fluorouracil, Carboplatin AUC
- Keywords
- WT1, neoadjuvant, tumor antigen, immunotherapy, breast cancer, adult
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024ABiological
Also called WT1 ASCI
6 or 8 injections at 3 weeks apart, injected intramuscularly in the deltoid or lateral region of the thigh.
PlaceboDrug
6 or 8 doses at 3 weeks apart of sucrose/mannitol-based formulation reconstituted with an oil-in-water emulsion, injected intramuscularly in the deltoid or lateral region of the thigh.
Aromatase inhibitorDrug
This treatment consisted of any aromatase inhibitor (e.g. letrozole or exemestane), administered intravenously in Cohort A Groups daily for either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo).
5-FluorouracilDrug
Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses at 3 weeks apart, and for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.
Carboplatin AUCDrug
Administered intravenously in Cohort C Groups in 6 doses at 3 weeks apart, on the same day as WT1 ASCI/placebo administration (Day 1 of each cycle).
CyclophosphamideDrug
Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses in Cohort C Groups and 6 doses 3 weeks apart in Cohorts A Placebo, B and D Groups, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.
DocetaxelDrug
Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.
DoxorubicinDrug
Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 6 doses 3 weeks apart (Cohort C patients with this schedule did not receive this treatment), while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.
EpirubicinDrug
Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.
PaclitaxelDrug
Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: only in the 8 WT1 ASCI-dose schedule patients received 4 at 3 weeks apart or 12 weekly doses. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.
TrastuzumabDrug
Administered intravenously in Cohort C Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohort B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A-GSK2302024A Group | Experimental | This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule. Receives: Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A; Drug: Aromatase inhibitor |
| Cohort A-Placebo Group | Placebo comparator | This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule. Receives: Drug: Placebo; Drug: Aromatase inhibitor; Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Doxorubicin; Drug: Epirubicin; Drug: Paclitaxel |
| Cohort B-GSK2302024A Group | Experimental | This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. Receives: Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A; Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Doxorubicin; Drug: Epirubicin; Drug: Paclitaxel |
| Cohort B-Placebo Group | Placebo comparator | This group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. Receives: Drug: Placebo; Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Doxorubicin; Drug: Epirubicin; Drug: Paclitaxel |
| Cohort C-GSK2302024A Group | Experimental | This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of GSK2302024A, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. Receives: Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A; Drug: 5-Fluorouracil; Drug: Carboplatin AUC; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Doxorubicin; Drug: Epirubicin; Drug: Paclitaxel; Drug: Trastuzumab |
| Cohort C-Placebo Group | Placebo comparator | This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. Receives: Drug: Placebo; Drug: 5-Fluorouracil; Drug: Carboplatin AUC; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Doxorubicin; Drug: Epirubicin; Drug: Paclitaxel; Drug: Trastuzumab |
| Cohort D-GSK2302024A-D14 Group | Experimental | This group included patients with hormone receptor-positive and HER2 non-overexpressing breast cancer, who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. Receives: Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A; Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Doxorubicin; Drug: Epirubicin; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Severe Toxicities
Severe toxicity was defined as follows: - A Grade 3 or higher toxicity that is related or possibly related to the combined administration of standard treatment and GSK2302024A/placebo - A decrease in Left Ventricular Ejection Fraction (LVEF) from baseline with ≥ 10 points and at < 50% that is related or possibly related to the combined administration of treatment and that is confirmed by a second LVEF assessment within approximately 3 weeks. - A Grade 2 or higher cardiac ischemia/infarction that is related or possibly related to the combined administration of standard treatment and GSK2302024A /placebo. - A Grade 2 or higher allergic reaction occurring within 24 hours following the administration. - A Grade 3 or higher blood/bone marrow toxicity that was considered as related or possibly related to the combined Administration. - A decrease in renal function at the time of administration that was considered as related or possibly related.
Measured: From Week 0 to Week 26/32 (period starting from GSK2302024A/placebo treatment allocation and ending with the concluding Visit i.e.: Week 26 for patients receiving 6 injections and Week 32 for patients receiving 8 injections)
Number of Patients With an Anti-Wilm's Tumor Gene (Anti-WT1) Humoral Response
For initially seronegative patients: post-administration antibody concentration ≥ 9 EU/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-administration antibody concentration.
Measured: At post-GSK2302024A/placebo Dose 4 (Week 13)
Number of Patients With Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical investigation patient, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse.
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Serious Adverse Events SAE(s)
A serious adverse event (SAE) is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of hospitalization, causes disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study patient. In this study, an event which was part of the natural course of the disease under study (i.e., disease progression/recurrence) was captured in the study/as an efficacy measure. Therefore it was not reported as an SAE. Progression/recurrence of the tumor was recorded in the clinical assessments in the electronic case report form (eCRF). Death due to progressive disease was recorded on a specific form in the eCRF but not as an SAE.
Measured: From Week 0 to Week 26/32 (period starting from GSK2302024A/placebo treatment allocation and ending with the concluding Visit i.e.: Week 26 for patients receiving 6 injections and Week 32 for patients receiving 8 injections)
Number of Subjects With Alanine Aminotransferase Increased Abnormality, by Common Terminology Criteria for Adverse Events (CTCAE) Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Alkaline Phosphatase Increased Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Anemia, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Aspartate Aminotransferase Increased Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Blood Bilirubin Increased Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Creatine Increased Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Hemoglobin Increased Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Hypercalcemia Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Hyperkalemia Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Hypernatremia Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Hypoalbuminemia Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Hypocalcemia Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Hypokalemia Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Hyponatremia Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and post 30 days post last administration
Number of Subjects With Lymphocyte Count Decreased Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Lymphocyte Count Increased Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Neutrophil Count Decreased Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Platelet Count Decreased Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With White Blood Cell Decreased Abnormality, by CTCAE Maximum Grade
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Patients With Adverse Events (AEs), by CTCAE Maximum Grade Reported
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Adverse Events (AEs) Assessed by the Investigators as Causally Related to GSK2302024A Treatment, by CTCAE Maximum Grade Reported
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Serious Adverse Events (SAEs), by CTCAE Maximum Grade Reported
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Serious Adverse Events (SAEs), Assessed by the Investigators as Causally Related to GSK2302024A Treatment, by CTCAE Maximum Grade Reported
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Measured: During the treatment period and up to 30 days post last administration
Number of Subjects With Breast Cancer Pathological Response
The pathological response in lymph nodes was evaluated by presence or absence of tumor cells by histopathological examination. Partial responses mark the disappearance of tumor cells, with only small clusters or dispersed cells remaining (more than 90% loss) while complete response indicate no identifiable malignant cells. However, ductal carcinoma in situ may be present.
Measured: During the treatment period, up to Week 26/32
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2010 (estimated)
- Study start11 Apr 2011
- Primary completion14 Nov 2014
- Study completion14 Nov 2014
Why it stopped: Study termination due to negative Ph III of another study product from same technology platform.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neoplasms, BreastStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01220128
- Sponsor's protocol ID
- 113172
- Other IDs
- 2010-019909-42
- Acronym
- INDUCT
- Status last verified
- Apr 2021
- First submitted
- 7 Oct 2010
- Last updated
- 25 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: IPD for this study is available via the Clinical Study Data Request site (click on the link provided below).
Publications
Higgins M, Curigliano G, Dieras V, Kuemmel S, Kunz G, Fasching PA, Campone M, Bachelot T, Krivorotko P, Chan S, Ferro A, Schwartzberg L, Gillet M, De Sousa Alves PM, Wascotte V, Lehmann FF, Goss P. Safety and immunogenicity of neoadjuvant treatment using WT1-immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II/III breast cancer: a randomized Phase I study. Breast Cancer Res Treat. 2017 Apr;162(3):479-488. doi: 10.1007/s10549-017-4130-y. Epub 2017 Feb 7.
PubMed 28176175
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of GSK2302024A Antigen-Specific Cancer Immunotherapeutic Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer
- ClinicalTrials.gov ID
- NCT01220128
- Acronym / sponsor ID
- INDUCT / 113172
- Conditions
- Neoplasms, Breast
- Keywords
- WT1, neoadjuvant, tumor antigen, immunotherapy, breast cancer, adult
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study termination due to negative Ph III of another study product from same technology platform.
- Enrolment
- 66 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 11 Apr 2011 (actual)
- Primary completion
- 14 Nov 2014 (actual)
- Study completion
- 14 Nov 2014 (actual)
- First posted
- 13 Oct 2010 (estimated)
- Results
- Posted 25 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, immunogenicity and clinical activity of a new WT1 anti-cancer immunotherapy in patients with WT1-positive Stage II or III breast cancer. The treatment will be given before surgery in combination with standard therapy.
Detailed description
The study will be conducted in two consecutive segments (Phase I and Phase II), each with specific objectives. Active follow-up will be for three years.
Patients in this study will be allocated to cohorts as below. Cohort A will include postmenopausal patients with hormone receptor-positive breast cancer who receive aromatase inhibitor (AI) as neoadjuvant therapy concurrently with administration of 6 or 8 doses of WT1 anti-cancer immunotherapy (WT1 ASCI)/placebo starting on Day 0. AI treatment will be administered daily for duration of either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo).
Cohort B will include breast cancer patients who will receive neoadjuvant chemotherapy concurrently with administration of WT1 ASCI/placebo starting on Day 0. Neoadjuvant chemotherapy in Cohort B will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly or 12-weekly taxane administrations without trastuzumab.
Cohort C will include patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who will receive neoadjuvant trastuzumab (Herceptin) therapy combined with chemotherapy concurrently with administration of WT1 ASCI/placebo starting on Day 0. Neoadjuvant chemotherapy in Cohort C will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly or 12-weekly taxane administrations with trastuzumab.
Cohorts D and E will include patients with hormone receptor-positive and HER2 non-overexpressing breast cancer who will receive neoadjuvant chemotherapy. For patients in these Cohorts D and E, WT1 ASCI/placebo (placebo applicable only for Cohort E patients) will be administered on Day 14 of each three-weekly cycle of chemotherapy. Neoadjuvant chemotherapy in Cohorts D and E will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly taxane administrations without trastuzumab. Enrolment in Cohort E will be conditional on the absence of a safety signal and on the adequate induction of an immune response by the WT1 ASCI in Cohort D (defined as >= 40% response rate based on post-Dose 4 anti-WT1 antibody responses in at least six patients). If this criterion is met, 60 patients (40 receiving WT1 ASCI and 20 placebo) with identical eligibility criteria will be enrolled into Cohort E. In case no adequate safety and/or immunogenicity will be obtained in Cohort D, recruitment in Cohort E will not be initiated.
The protocol has been updated following Protocol Amendment 4, April 2013, leading to the update of the study design.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Cohort A-GSK2302024A Group | Experimental | Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A, Drug: Aromatase inhibitorThis group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule. |
| Cohort A-Placebo Group | Placebo comparator | Drug: Placebo, Drug: Aromatase inhibitor, Drug: 5-Fluorouracil, Drug: Cyclophosphamide, Drug: Docetaxel, Drug: Doxorubicin, Drug: Epirubicin, Drug: PaclitaxelThis group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule. |
| Cohort B-GSK2302024A Group | Experimental | Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A, Drug: 5-Fluorouracil, Drug: Cyclophosphamide, Drug: Docetaxel, Drug: Doxorubicin, Drug: Epirubicin, Drug: PaclitaxelThis group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. |
| Cohort B-Placebo Group | Placebo comparator | Drug: Placebo, Drug: 5-Fluorouracil, Drug: Cyclophosphamide, Drug: Docetaxel, Drug: Doxorubicin, Drug: Epirubicin, Drug: PaclitaxelThis group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. |
| Cohort C-GSK2302024A Group | Experimental | Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A, Drug: 5-Fluorouracil, Drug: Carboplatin AUC, Drug: Cyclophosphamide, Drug: Docetaxel, Drug: Doxorubicin, Drug: Epirubicin, Drug: Paclitaxel, Drug: TrastuzumabThis group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of GSK2302024A, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. |
| Cohort C-Placebo Group | Placebo comparator | Drug: Placebo, Drug: 5-Fluorouracil, Drug: Carboplatin AUC, Drug: Cyclophosphamide, Drug: Docetaxel, Drug: Doxorubicin, Drug: Epirubicin, Drug: Paclitaxel, Drug: TrastuzumabThis group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. |
| Cohort D-GSK2302024A-D14 Group | Experimental | Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A, Drug: 5-Fluorouracil, Drug: Cyclophosphamide, Drug: Docetaxel, Drug: Doxorubicin, Drug: Epirubicin, Drug: PaclitaxelThis group included patients with hormone receptor-positive and HER2 non-overexpressing breast cancer, who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- The patient is ≥ 18 years of age at the time the informed consent to screening has been obtained.
- The patient has proven T1 with lymph node involvement or T2-T4c, any N, M0 primary invasive breast cancer, histologically confirmed by core needle biopsy.
- Isolated supraclavicular lymph node involvement is allowed.
- The patient's tumor shows WT1 antigen expression.
- The patient has one of the following histologically confirmed breast cancer subtypes:
Key exclusion criteria (13 listed)
- The patient has inflammatory breast cancer, which is defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion.
- Diagnosis established by incisional biopsy.
- Prior and concomitant neoadjuvant anti-breast-cancer treatments such as chemotherapy, immunotherapy / biological response modifiers, endocrine therapy, and radiotherapy, unless authorized specifically by the protocol.
- The patient is known to be human immunodeficiency virus -positive.
- The patient has symptomatic autoimmune disease such as, but not limited to multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024AAlso: WT1 ASCI6 or 8 injections at 3 weeks apart, injected intramuscularly in the deltoid or lateral region of the thigh. | Biological | Cohort A-GSK2302024A Group, Cohort B-GSK2302024A Group, Cohort C-GSK2302024A Group, Cohort D-GSK2302024A-D14 Group |
| Placebo6 or 8 doses at 3 weeks apart of sucrose/mannitol-based formulation reconstituted with an oil-in-water emulsion, injected intramuscularly in the deltoid or lateral region of the thigh. | Drug | Cohort A-Placebo Group, Cohort B-Placebo Group, Cohort C-Placebo Group |
| Aromatase inhibitorThis treatment consisted of any aromatase inhibitor (e.g. letrozole or exemestane), administered intravenously in Cohort A Groups daily for either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo). | Drug | Cohort A-GSK2302024A Group, Cohort A-Placebo Group |
| 5-FluorouracilAdministered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses at 3 weeks apart, and for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle. | Drug | Cohort A-Placebo Group, Cohort B-GSK2302024A Group, Cohort B-Placebo Group, Cohort C-GSK2302024A Group, Cohort C-Placebo Group, Cohort D-GSK2302024A-D14 Group |
| Carboplatin AUCAdministered intravenously in Cohort C Groups in 6 doses at 3 weeks apart, on the same day as WT1 ASCI/placebo administration (Day 1 of each cycle). | Drug | Cohort C-GSK2302024A Group, Cohort C-Placebo Group |
| CyclophosphamideAdministered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses in Cohort C Groups and 6 doses 3 weeks apart in Cohorts A Placebo, B and D Groups, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle. | Drug | Cohort A-Placebo Group, Cohort B-GSK2302024A Group, Cohort B-Placebo Group, Cohort C-GSK2302024A Group, Cohort C-Placebo Group, Cohort D-GSK2302024A-D14 Group |
| DocetaxelAdministered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle. | Drug | Cohort A-Placebo Group, Cohort B-GSK2302024A Group, Cohort B-Placebo Group, Cohort C-GSK2302024A Group, Cohort C-Placebo Group, Cohort D-GSK2302024A-D14 Group |
| DoxorubicinAdministered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 6 doses 3 weeks apart (Cohort C patients with this schedule did not receive this treatment), while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle. | Drug | Cohort A-Placebo Group, Cohort B-GSK2302024A Group, Cohort B-Placebo Group, Cohort C-GSK2302024A Group, Cohort C-Placebo Group, Cohort D-GSK2302024A-D14 Group |
| EpirubicinAdministered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle. | Drug | Cohort A-Placebo Group, Cohort B-GSK2302024A Group, Cohort B-Placebo Group, Cohort C-GSK2302024A Group, Cohort C-Placebo Group, Cohort D-GSK2302024A-D14 Group |
| PaclitaxelAdministered intravenously in Cohorts A Placebo, B, C and D/E Groups: only in the 8 WT1 ASCI-dose schedule patients received 4 at 3 weeks apart or 12 weekly doses. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle. | Drug | Cohort A-Placebo Group, Cohort B-GSK2302024A Group, Cohort B-Placebo Group, Cohort C-GSK2302024A Group, Cohort C-Placebo Group, Cohort D-GSK2302024A-D14 Group |
| TrastuzumabAdministered intravenously in Cohort C Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohort B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle. | Drug | Cohort C-GSK2302024A Group, Cohort C-Placebo Group |
Primary outcome
Number of Subjects With Severe Toxicities
Time frame: From Week 0 to Week 26/32 (period starting from GSK2302024A/placebo treatment allocation and ending with the concluding Visit i.e.: Week 26 for patients receiving 6 injections and Week 32 for patients receiving 8 injections)
Severe toxicity was defined as follows: - A Grade 3 or higher toxicity that is related or possibly related to the combined administration of standard treatment and GSK2302024A/placebo - A decrease in Left Ventricular Ejection Fraction (LVEF) from baseline with ≥ 10 points and at < 50% that is related or possibly related to the combined administration of treatment and that is confirmed by a second LVEF assessment within approximately 3 weeks. - A Grade 2 or higher cardiac ischemia/infarction that is related or possibly related to the combined administration of standard treatment and GSK2302024A /placebo. - A Grade 2 or higher allergic reaction occurring within 24 hours following the administration. - A Grade 3 or higher blood/bone marrow toxicity that was considered as related or possibly related to the combined Administration. - A decrease in renal function at the time of administration that was considered as related or possibly related.
Number of Patients With an Anti-Wilm's Tumor Gene (Anti-WT1) Humoral Response
Time frame: At post-GSK2302024A/placebo Dose 4 (Week 13)
For initially seronegative patients: post-administration antibody concentration ≥ 9 EU/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-administration antibody concentration.
Number of Patients With Adverse Events (AEs)
Time frame: During the treatment period and up to 30 days post last administration
An AE is any untoward medical occurrence in a clinical investigation patient, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse.
Number of Subjects With Serious Adverse Events SAE(s)
Time frame: From Week 0 to Week 26/32 (period starting from GSK2302024A/placebo treatment allocation and ending with the concluding Visit i.e.: Week 26 for patients receiving 6 injections and Week 32 for patients receiving 8 injections)
A serious adverse event (SAE) is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of hospitalization, causes disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study patient. In this study, an event which was part of the natural course of the disease under study (i.e., disease progression/recurrence) was captured in the study/as an efficacy measure. Therefore it was not reported as an SAE. Progression/recurrence of the tumor was recorded in the clinical assessments in the electronic case report form (eCRF). Death due to progressive disease was recorded on a specific form in the eCRF but not as an SAE.
Number of Subjects With Alanine Aminotransferase Increased Abnormality, by Common Terminology Criteria for Adverse Events (CTCAE) Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Alkaline Phosphatase Increased Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Anemia, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Aspartate Aminotransferase Increased Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Blood Bilirubin Increased Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Creatine Increased Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Hemoglobin Increased Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Hypercalcemia Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Hyperkalemia Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Hypernatremia Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Hypoalbuminemia Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Hypocalcemia Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Hypokalemia Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Hyponatremia Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and post 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Lymphocyte Count Decreased Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Lymphocyte Count Increased Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Neutrophil Count Decreased Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Platelet Count Decreased Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With White Blood Cell Decreased Abnormality, by CTCAE Maximum Grade
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Patients With Adverse Events (AEs), by CTCAE Maximum Grade Reported
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Adverse Events (AEs) Assessed by the Investigators as Causally Related to GSK2302024A Treatment, by CTCAE Maximum Grade Reported
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Serious Adverse Events (SAEs), by CTCAE Maximum Grade Reported
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Serious Adverse Events (SAEs), Assessed by the Investigators as Causally Related to GSK2302024A Treatment, by CTCAE Maximum Grade Reported
Time frame: During the treatment period and up to 30 days post last administration
Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).
Number of Subjects With Breast Cancer Pathological Response
Time frame: During the treatment period, up to Week 26/32
The pathological response in lymph nodes was evaluated by presence or absence of tumor cells by histopathological examination. Partial responses mark the disappearance of tumor cells, with only small clusters or dispersed cells remaining (more than 90% loss) while complete response indicate no identifiable malignant cells. However, ductal carcinoma in situ may be present.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28176175Higgins M, Curigliano G, Dieras V, Kuemmel S, Kunz G, Fasching PA, Campone M, Bachelot T, Krivorotko P, Chan S, Ferro A, Schwartzberg L, Gillet M, De Sousa Alves PM, Wascotte V, Lehmann FF, Goss P. Safety and immunogenicity of neoadjuvant treatment using WT1-immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II/III breast cancer: a randomized Phase I study. Breast Cancer Res Treat. 2017 Apr;162(3):479-488. doi: 10.1007/s10549-017-4130-y. Epub 2017 Feb 7.
- Individual participant dataSharing planned: Yes. IPD for this study is available via the Clinical Study Data Request site (click on the link provided below).
Related trials for Neoplasms, Breast
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
36 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A, Aromatase inhibitor and 5-Fluorouracil in people with Neoplasms, Breast, run by GlaxoSmithKline at 36 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States, Germany, Italy, United Kingdom, Belgium and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Severe Toxicities (time frame: From Week 0 to Week 26/32 (period starting from GSK2302024A/placebo treatment allocation and ending with the concluding Visit i.e.: Week 26 for patients receiving 6 injections and Week 32 for patients receiving 8 injections)). The study lists 28 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01220128, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2021.