Tubular Breast Cancer Stage IIPhase 3NCT02125344
A Phase III Trial Comparing Two Dose-dense, Dose-intensified Approaches (ETC and PM(Cb)) for Neoadjuvant Treatment of Patients With High-risk Early Breast Cancer (GeparOcto)
A Phase 3 study testing non-pegylated liposomal doxorubicin, Carboplatin and Paclitaxel in people with Tubular Breast Cancer Stage II and Tubular Breast Cancer Stage III, run by GBG Forschungs GmbH at 1 site in Germany.
Trial summary
Two regimen are currently considered to have highest efficacy for patients with high-risk early stage breast cancer: sequential treatment of high dose epirubicin, taxane, and cyclophosphamide concomitantly with a dual HER2-blockade, and weekly treatment with paclitaxel/non-pegylated liposomal doxorubicin with dual… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Tubular Breast Cancer Stage II, Tubular Breast Cancer Stage III, Mucinous Breast Cancer Stage II
- What is being tested?
- non-pegylated liposomal doxorubicin, Carboplatin and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 961 participants
- Where
- 1 siteGermany
- Study dates
- Dec 2014to 30 Jan 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients will be eligible for study participation only if they comply with the following criteria:
- Written informed consent according to local regulatory requirements prior to beginning specific protocol procedures.
- Complete baseline documentation must be submitted via MedCODES to GBG Forschungs GmbH.
- Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration from the breast lesion alone is not sufficient. Incisional biopsy or axillary clearance is not allowed.
- In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint.
- Tumor lesion in the breast with a palpable size of 2 cm or a sonographical size of 1 cm in maximum diameter. The lesion has to be measurable in two dimensions, preferably by sonography. In case of inflammatory disease, the extent of inflammation can be used as measurable lesion.
Show all 20Show fewer
- Patients must have stage cT1c - cT4a-d disease. Patients with HER2- positive or TNBC are eligible irrespective of nodal status (cN0-cN3). Patients with luminal B-like tumors (defined here as ER and/or PgR >1% stained cells, HER2 negative, Ki-67 >20%) only with histologically (sentinel-node biopsy, core- or fine-needle biopsy) involved lymph nodes (pN1-3).
- In patients with multifocal or multicentric breast cancer, the largest lesion should be measured.
- Centrally confirmed ER, PR and HER2 status. Central pathology includes also assessment of Ki-67 and LPBC status on core biopsy. ER/PR negative is defined as <=1% stained cells and HER2-positive is defined as IHC 3+ or in-situ hybridization (ISH) and according to ASCO-CAP guidelines as of 2013). Formalin-fixed, paraffin-embedded (FFPE) breast tissue from core biopsy has therefore to be sent to the GBG central pathology laboratory prior to randomization.
- Age >=18 years.
- Karnofsky Performance status index 90%.
- Confirmed normal cardiac function by ECG and cardiac ultrasound (LVEF or shortening fraction) within 4 weeks prior to randomization. LVEF must be above 55%.
- Negative pregnancy test (urine or serum) within 14 days prior to randomization for all women of childbearing potential.
- Complete staging work-up within 3 months prior to randomization. All patients must have bilateral mammography, breast ultrasound (21 days), breast MRI (optional). Chest X-ray (PA and lateral), abdominal ultrasound or CT scan or MRI, and bone scan in case of high risk for primary metastasis. In case of a positive bone scan, bone X-ray or CT scan is mandatory. Other tests may be performed as clinically indicated.
- Patients must agree with central pathology testing of core biopsy specimen and final pathology specimen and be available and compliant for treatment and follow-up.
- In addition for patients to be randomized to the two supportive anemia treatment arms:
- Hemoglobin level <10g/dl.
- Body weight ≥ 40 kg.
- No need for immediate red blood cell transfusion.
- Transferrin saturation (TSAT) ≤20% and serum ferritin <300ng/ml.
Who cannot join
- Patients with ER- and/or PR-positive, HER2-negative breast cancer and Ki- 67 <= 20% (any luminal A-like subtype) or luminal B-like (Ki67>20%) subtype without nodal involvement.
- Patients with stages cT1a, cT1b, or any M1.
- Patients with pure lobular invasive breast cancer.
- Prior chemotherapy for any malignancy.
- Prior radiation therapy for breast cancer.
- Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment.
Show all 24Show fewer
- Inadequate general condition (not fit for dose-dense, dose-intensified anthracycline-taxane-targeted agents-based chemotherapy).
- Previous malignant disease being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
- Known or suspected congestive heart failure (>NYHA I) and / or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP >140/90 mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
- History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.
- Pre-existing motor or sensory neuropathy of a severity grade 2 by NCI-CTC criteria v 4.0.
- Currently active infection.
- Incomplete wound healing.
- Definite contraindications for the use of corticosteroids.
- Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol.
- Concurrent treatment with:
- chronic corticosteroids unless initiated > 6 months prior to study entry and at low dose (10 mg or less methylprednisolone or equivalent).
- sex hormones. Prior treatment must be stopped before study entry.
- other experimental drugs or any other anti-cancer therapy.
- Participation in another clinical trial with any investigational, not marketed drug within 30 days prior to study entry.
- Male patients.
- In addition for patients to be randomized to the two supportive anemia treatment arms:
- Iron substitution (oral or IV) or blood transfusions or treatment with r-HuEPO with the last 4 weeks prior to study start.
- Known hypersensibility or contraindication against ferric carboxymaltose.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Phase III Trial Comparing Two Dose-dense, Dose-intensified Approaches (ETC and PM(Cb)) for Neoadjuvant Treatment of Patients With High-risk Early Breast Cancer (GeparOcto)
Two regimen are currently considered to have highest efficacy for patients with high-risk early stage breast cancer: sequential treatment of high dose epirubicin, taxane, and cyclophosphamide concomitantly with a dual HER2-blockade, and weekly treatment with paclitaxel/non-pegylated liposomal doxorubicin with dual HER2-blockade or carboplatin. The aim of the GeparOcto study is to compare those two regimen/strategies.
Both regimens are myelosuppressive with a significant incidence of chemotherapy induced anaemia.
The second aim of the GeparOcto study is therefore to compare the use of parental ferric carboxymaltose versus physician's choice for the treatment of chemotherapy-induced anemia in patients with iron deficiency.
Read the detailed description
Several recent strategies have improved efficacy of systemic treatment for patients with high-risk early stage breast cancer: the addition of a dual HER2-blockade for HER2-positive; the implementation of carboplatin for TNBC and the use of dose-dense or dose-dense, dose escalated chemotherapy in all high-risk subtypes of breast cancer. Two regimen are currently considered to have highest efficacy: sequential treatment of high dose epirubicin, taxane, and cyclophosphamide (ETC) concomitantly with a dual HER2-blockade mainly based on the AGO ETC adjuvant study, and weekly treatment with paclitaxel/non-pegylated liposomal doxorubicin with dual HER2-blockade or carboplatin (PM(Cb)) based on the GeparSixto study. The aim of the GeparOcto study is to compare those two regimen/strategies.
Both regimens are myelosuppressive with a significant incidence of chemotherapy induced anaemia. Anemia is often associated with impaired physical and cognitive function and consequently the patients suffer from a reduced quality of life. Surgical complications are higher in anemic patients. The second aim of the GeparOcto study is therefore to compare the use of parental ferric carboxymaltose versus physician's choice for the treatment of chemotherapy-induced anemia in patients with iron deficiency.
- Conditions
- Tubular Breast Cancer Stage II, Tubular Breast Cancer Stage III, Mucinous Breast Cancer Stage II, Breast Cancer Female NOS, Invasive Ductal Breast Cancer, HER2 Positive Breast Cancer
- Being tested
- non-pegylated liposomal doxorubicin, Carboplatin, Paclitaxel, Epirubicin, Cyclophosphamide
- Medical subject headings
- Carcinoma, Ductal, Breast, Inflammatory Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
non-pegylated liposomal doxorubicinDrug
Also called Myocet
20 mg/m2, i.V. 18 times weekly
CarboplatinDrug
Also called Carbomedac
Carboplatin AUC 1.5 18 times weekly (only in patients with triple-negative breast cancer).
PaclitaxelDrug
Also called var.
paclitaxel 80mg/m² 18 times weekly
EpirubicinDrug
Also called Farmorubicin
150mg/m² every 2 weeks for 3 cycles.
CyclophosphamideDrug
Also called Endoxan
2000 mg/m² every 2 weeks for 3 cycles.
PertuzumabDrug
Also called Perjeta
420 (840) mg every 3 weeks simultaneously to all T and C cycles in the ETC arm and to all cycles in the PM(Cb) arm.
TrastuzumabDrug
Also called Herceptin
Trastuzumab 6 (8) mg/kg every 3 weeks simultaneously to all T and C cycles in the ETC arm and to all cycles in the PM(Cb) arm.
Ferric carboxymaltoseDrug
Also called Ferinject
after first anemia grade ≥2 and in case of randomisation: Ferric carboxymaltose i.V. 1000 mg followed 1 week later by an injection of ferric carboxymaltose i.V. 500 mg (if body weight is <70 kg) or 1000 mg (if body weight is ≥70 kg). In case body weight is <50 kg, both dosages will be reduced to 500 mg each.
| Study group | Role | What they receive |
|---|---|---|
| PM(Cb) | Experimental | PM(Cb):
paclitaxel 80mg/m² 18 times weekly simultaneously with NPLD (Myocet®)20mg/m² 18 times weekly simultaneously with carboplatin AUC 1.5 18 times weekly (only in patients with TNBC) Patients with HER2-positive disease will receive trastuzumab 6 (8) mg/kg every 3 weeks and pertuzumab 420 (840) mg every 3 weeks simultaneously to all cycles. Receives: Drug: non-pegylated liposomal doxorubicin; Drug: Carboplatin; Drug: Paclitaxel; Drug: Pertuzumab; Drug: Trastuzumab; Drug: Ferric carboxymaltose |
| ETC | Active comparator | ETC:
epirubicin 150mg/m² every 2 weeks for 3 cycles followed by paclitaxel 225 mg/m² every 2 weeks for 3 cycles followed cyclophosphamide 2000 mg/m² every 2 weeks for 3 cycles. Patients with HER2-positive disease will receive trastuzumab 6 (8) mg/kg every 3 weeks and pertuzumab 420 (840) mg every 3 weeks simultaneously to all T and C cycles. Receives: Drug: Paclitaxel; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Pertuzumab; Drug: Trastuzumab; Drug: Ferric carboxymaltose |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathological complete response (pCR= ypT0/is ypN0)
To compare the pathological complete response (pCR= ypT0/is ypN0) rates of neoadjuvant treatment with sequential, dose-dense, dose-intensified ETC(+HP) vs. weekly PM(Cb)(+HP) in patients with high-risk operable or locally advanced breast cancer.
Masked role for assessor.
Measured: 18 weeks (time window + 3 weeks)
Only for those patients randomized for the supportive anemia treatment: frequency of patients reaching hemoglobin (Hb) levels ≥ 11g/dl 6 weeks after treatment start of a first episode of anemia grade ≥2
Only for those patients randomized for the supportive anemia treatment:
To compare the frequency of patients reaching hemoglobin (Hb) levels ≥ 11g/dl 6 weeks after treatment start of a first episode of anemia grade ≥2 (Hb < 10g/dl) between patients receiving supportive treatment for iron deficiency with parental ferric carboxymaltose versus physician's choice (no supportive treatment, oral iron substitution, erythropoiesis-stimulating agent (ESA), or both).
Measured: 18 weeks (time window + 3 weeks)
Secondary outcomes (20)
pcR rates per arm
To assess the pCR rates per arm separately for the stratified subpopulations.
Measured: 18 weeks (time frame + 3 weeks)
Clinical and imaging response
To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in both arms.
Measured: 18 weeks (time window + 3 weeks)
Rates of ypT0 ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0; and the residual cancer burden (RCB) score.
Response (by physical examination, imaging response, breast conservation) will also be summarized as rates in each treatment group).
Measured: 18 weeks (time frame + 3 weeks)
Toxicity and Compliance including incidence of febrile neutropenia
Descriptive statistics for the 5 treatments (ETC +/- anti-HER2-treatment, PM +/- anti-HER2-treatment, PMCb) will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped.
Measured: 18 weeks (time frame + 3 weeks)
Breast conservation rate
To determine the breast conservation rate after each treatment.
Measured: 18 weeks (time frame: + 3 weeks)
loco-regional invasive recurrence free survival (LRRFS) in both arms and according to stratified subpopulations
LRRFS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.
Measured: 5 years
distant-disease-free survival (DDFS) in both arms and according to stratified subpopulations.
DDFS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.
Measured: 5 years
invasive disease-free survival (IDFS) in both arms and according to stratified subpopulations.
IDFS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.
Measured: 5 years
overall survival (OS) in both arms and according to stratified subpopulations.
OS is defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.
Measured: 5 years
regional recurrence free survival (RRFS) in patients with initial node-positive axilla
To assess regional recurrence free survival (RRFS) in patients with initial node-positive axilla converted to negative (ypN0) at surgery and treated with sentinel node biopsy alone.
Measured: until event occurs - no event for cured patients
pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy
To determine the pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery.
Measured: 5 years
Correlation of response
To correlate response (complete vs. partial vs. no change) measured by best appropriate imaging method after 6 weeks of treatment with pCR.
Measured: 18 weeks (time frame + 3 weeks)
Examination and comparison of molecular markers
To examine and compare pre-specified molecular and histological markers such as Ki67, stromal TILs, immunologically relevant genes (e.g. CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21, IDO1, PD-1, PDL1, CTLA4, FOXP3, and combinations of these genes) as well as e.g. CD138, CD47, MET and other markers on core biopsies before and eventually also on surgical tissue after end of chemotherapy.
The aim is to identify potential predictive short and long term parameters.
Measured: Baseline and 18 weeks (time frame + 3 weeks)
Examination of PIK3CA mutation
To examine PIK3CA mutation in patients with HER2-positive tumor on core biopsies.
Measured: Baseline and 18 weeks (time frame + 3 weeks)
Only for those patients randomized for the supportive anemia treatment: Quality of life
To compare quality of life using the FACT-An anemia and fatigue questionnaire between the supportive treatment arms.
Measured: up to 18 weeks
Only for those patients randomized for the supportive anemia treatment: median time to achieve a hemoglobin level ≥11g/dl
To compare the median time to achieve a hemoglobin level ≥11g/dl between the supportive treatment arms.
Measured: up to 18 weeks
Only for those patients randomized for the supportive anemia treatment: frequency of patients with a hemoglobin level ≥11g/dl
To compare the frequency of patients with hemoglobin level ≥11g/dl in the week after the end of the last chemotherapy cycle between the supportive treatment arms.
Measured: up to 18 weeks
Pharmacogenetic substudy
To correlate Single Nucleotide Polymorphisms (SNPs) of genes with the associated toxicity and histologically assessed treatment effect.
Measured: 18 weeks (time frame + 3 weeks)
GeparPET substudy
To demonstrate that PET-CT before surgery in addition to conventional presurgical staging methods can decrease the mastectomy rate in patients receiving neoadjuvant chemotherapy for breast cancer.
Measured: 18 weeks (time frame + 3 weeks)
Ovarian function
To assess ovarian function measured by amenorrhea rate in correlation with changes in E2, FSH, LH , Anti-Müller Hormone, ultrasound-follicle count in patients aged <45 years.
Measured: Baseline until 2 years after EOS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2014 (estimated)
- Study startDec 2014
- Primary completionNov 2016
- Study completion30 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Tubular Breast Cancer Stage IIStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 961 participants (actual)
Sponsor and investigators
- Lead sponsor
- GBG Forschungs GmbH
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen, Roche Pharma AG, Teva Pharmaceuticals USA, Vifor Pharma
- Responsible party
- Sponsor
- Investigators
- Andreas Schneeweiss, MD, Prof., Principal investigator, NTC Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02125344
- Sponsor's protocol ID
- GBG 84
- Status last verified
- Jul 2017
- First submitted
- 22 Apr 2014
- Last updated
- 13 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Schneeweiss A, Michel LL, Mobus V, Tesch H, Klare P, Hahnen E, Denkert C, Kast K, Pohl-Rescigno E, Hanusch C, Link T, Untch M, Jackisch C, Blohmer JU, Fasching PA, Solbach C, Schmutzler RK, Huober J, Rhiem K, Nekljudova V, Lubbe K, Loibl S; GBG and AGO-B. Survival analysis of the randomised phase III GeparOcto trial comparing neoadjuvant chemotherapy of intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for patients with high-risk early breast cancer. Eur J Cancer. 2022 Jan;160:100-111. doi: 10.1016/j.ejca.2021.10.011. Epub 2021 Nov 17.
PubMed 34801353Denkert C, Seither F, Schneeweiss A, Link T, Blohmer JU, Just M, Wimberger P, Forberger A, Tesch H, Jackisch C, Schmatloch S, Reinisch M, Solomayer EF, Schmitt WD, Hanusch C, Fasching PA, Lubbe K, Solbach C, Huober J, Rhiem K, Marme F, Reimer T, Schmidt M, Sinn BV, Janni W, Stickeler E, Michel L, Stotzer O, Hahnen E, Furlanetto J, Seiler S, Nekljudova V, Untch M, Loibl S. Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials. Lancet Oncol. 2021 Aug;22(8):1151-1161. doi: 10.1016/S1470-2045(21)00301-6. Epub 2021 Jul 9.
PubMed 34252375Ruger AM, Schneeweiss A, Seiler S, Tesch H, van Mackelenbergh M, Marme F, Lubbe K, Sinn B, Karn T, Stickeler E, Muller V, Schem C, Denkert C, Fasching PA, Nekljudova V, Garfias-Macedo T, Hasenfuss G, Haverkamp W, Loibl S, von Haehling S. Cardiotoxicity and Cardiovascular Biomarkers in Patients With Breast Cancer: Data From the GeparOcto-GBG 84 Trial. J Am Heart Assoc. 2020 Dec;9(23):e018143. doi: 10.1161/JAHA.120.018143. Epub 2020 Nov 16.
PubMed 33191846Pohl-Rescigno E, Hauke J, Loibl S, Mobus V, Denkert C, Fasching PA, Kayali M, Ernst C, Weber-Lassalle N, Hanusch C, Tesch H, Muller V, Altmuller J, Thiele H, Untch M, Lubbe K, Nurnberg P, Rhiem K, Furlanetto J, Lederer B, Jackisch C, Nekljudova V, Schmutzler RK, Schneeweiss A, Hahnen E. Association of Germline Variant Status With Therapy Response in High-risk Early-Stage Breast Cancer: A Secondary Analysis of the GeparOcto Randomized Clinical Trial. JAMA Oncol. 2020 May 1;6(5):744-748. doi: 10.1001/jamaoncol.2020.0007.
PubMed 32163106Schneeweiss A, Mobus V, Tesch H, Hanusch C, Denkert C, Lubbe K, Huober J, Klare P, Kummel S, Untch M, Kast K, Jackisch C, Thomalla J, Ingold-Heppner B, Blohmer JU, Rezai M, Frank M, Engels K, Rhiem K, Fasching PA, Nekljudova V, von Minckwitz G, Loibl S. Intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto-GBG 84): A randomised phase III trial. Eur J Cancer. 2019 Jan;106:181-192. doi: 10.1016/j.ejca.2018.10.015. Epub 2018 Dec 5.
PubMed 30528802
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase III Trial Comparing Two Dose-dense, Dose-intensified Approaches (ETC and PM(Cb)) for Neoadjuvant Treatment of Patients With High-risk Early Breast Cancer (GeparOcto)
- ClinicalTrials.gov ID
- NCT02125344
- Acronym / sponsor ID
- GBG 84
- Conditions
- Tubular Breast Cancer Stage II, Tubular Breast Cancer Stage III, Mucinous Breast Cancer Stage II, Breast Cancer Female NOS, Invasive Ductal Breast Cancer, HER2 Positive Breast Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 961 participants (actual)
- Lead sponsor
- GBG Forschungs GmbHUniversity, hospital or other
- Collaborators
- Amgen, Roche Pharma AG, Teva Pharmaceuticals USA, Vifor Pharma
- Study start
- Dec 2014 (actual)
- Primary completion
- Nov 2016 (actual)
- Study completion
- 30 Jan 2017 (actual)
- First posted
- 29 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Two regimen are currently considered to have highest efficacy for patients with high-risk early stage breast cancer: sequential treatment of high dose epirubicin, taxane, and cyclophosphamide concomitantly with a dual HER2-blockade, and weekly treatment with paclitaxel/non-pegylated liposomal doxorubicin with dual HER2-blockade or carboplatin. The aim of the GeparOcto study is to compare those two regimen/strategies.
Both regimens are myelosuppressive with a significant incidence of chemotherapy induced anaemia.
The second aim of the GeparOcto study is therefore to compare the use of parental ferric carboxymaltose versus physician's choice for the treatment of chemotherapy-induced anemia in patients with iron deficiency.
Detailed description
Several recent strategies have improved efficacy of systemic treatment for patients with high-risk early stage breast cancer: the addition of a dual HER2-blockade for HER2-positive; the implementation of carboplatin for TNBC and the use of dose-dense or dose-dense, dose escalated chemotherapy in all high-risk subtypes of breast cancer. Two regimen are currently considered to have highest efficacy: sequential treatment of high dose epirubicin, taxane, and cyclophosphamide (ETC) concomitantly with a dual HER2-blockade mainly based on the AGO ETC adjuvant study, and weekly treatment with paclitaxel/non-pegylated liposomal doxorubicin with dual HER2-blockade or carboplatin (PM(Cb)) based on the GeparSixto study. The aim of the GeparOcto study is to compare those two regimen/strategies.
Both regimens are myelosuppressive with a significant incidence of chemotherapy induced anaemia. Anemia is often associated with impaired physical and cognitive function and consequently the patients suffer from a reduced quality of life. Surgical complications are higher in anemic patients. The second aim of the GeparOcto study is therefore to compare the use of parental ferric carboxymaltose versus physician's choice for the treatment of chemotherapy-induced anemia in patients with iron deficiency.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PM(Cb) | Experimental | Drug: non-pegylated liposomal doxorubicin, Drug: Carboplatin, Drug: Paclitaxel, Drug: Pertuzumab, Drug: Trastuzumab, Drug: Ferric carboxymaltosePM(Cb): paclitaxel 80mg/m² 18 times weekly simultaneously with NPLD (Myocet®)20mg/m² 18 times weekly simultaneously with carboplatin AUC 1.5 18 times weekly (only in patients with TNBC) Patients with HER2-positive disease will receive trastuzumab 6 (8) mg/kg every 3 weeks and pertuzumab 420 (840) mg every 3 weeks simultaneously to all cycles. |
| ETC | Active comparator | Drug: Paclitaxel, Drug: Epirubicin, Drug: Cyclophosphamide, Drug: Pertuzumab, Drug: Trastuzumab, Drug: Ferric carboxymaltoseETC: epirubicin 150mg/m² every 2 weeks for 3 cycles followed by paclitaxel 225 mg/m² every 2 weeks for 3 cycles followed cyclophosphamide 2000 mg/m² every 2 weeks for 3 cycles. Patients with HER2-positive disease will receive trastuzumab 6 (8) mg/kg every 3 weeks and pertuzumab 420 (840) mg every 3 weeks simultaneously to all T and C cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients will be eligible for study participation only if they comply with the following criteria:
- Written informed consent according to local regulatory requirements prior to beginning specific protocol procedures.
- Complete baseline documentation must be submitted via MedCODES to GBG Forschungs GmbH.
- Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration from the breast lesion alone is not sufficient. Incisional biopsy or axillary clearance is not allowed.
- In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint.
Key exclusion criteria (24 listed)
- Patients with ER- and/or PR-positive, HER2-negative breast cancer and Ki- 67 <= 20% (any luminal A-like subtype) or luminal B-like (Ki67>20%) subtype without nodal involvement.
- Patients with stages cT1a, cT1b, or any M1.
- Patients with pure lobular invasive breast cancer.
- Prior chemotherapy for any malignancy.
- Prior radiation therapy for breast cancer.
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 |
|---|---|---|
| non-pegylated liposomal doxorubicinAlso: Myocet20 mg/m2, i.V. 18 times weekly | Drug | PM(Cb) |
| CarboplatinAlso: CarbomedacCarboplatin AUC 1.5 18 times weekly (only in patients with triple-negative breast cancer). | Drug | PM(Cb) |
| PaclitaxelAlso: var.paclitaxel 80mg/m² 18 times weekly | Drug | ETC, PM(Cb) |
| EpirubicinAlso: Farmorubicin150mg/m² every 2 weeks for 3 cycles. | Drug | ETC |
| CyclophosphamideAlso: Endoxan2000 mg/m² every 2 weeks for 3 cycles. | Drug | ETC |
| PertuzumabAlso: Perjeta420 (840) mg every 3 weeks simultaneously to all T and C cycles in the ETC arm and to all cycles in the PM(Cb) arm. | Drug | ETC, PM(Cb) |
| TrastuzumabAlso: HerceptinTrastuzumab 6 (8) mg/kg every 3 weeks simultaneously to all T and C cycles in the ETC arm and to all cycles in the PM(Cb) arm. | Drug | ETC, PM(Cb) |
| Ferric carboxymaltoseAlso: Ferinjectafter first anemia grade ≥2 and in case of randomisation: Ferric carboxymaltose i.V. 1000 mg followed 1 week later by an injection of ferric carboxymaltose i.V. 500 mg (if body weight is <70 kg) or 1000 mg (if body weight is ≥70 kg). In case body weight is <50 kg, both dosages will be reduced to 500 mg each. | Drug | ETC, PM(Cb) |
Primary outcome
pathological complete response (pCR= ypT0/is ypN0)
Time frame: 18 weeks (time window + 3 weeks)
To compare the pathological complete response (pCR= ypT0/is ypN0) rates of neoadjuvant treatment with sequential, dose-dense, dose-intensified ETC(+HP) vs. weekly PM(Cb)(+HP) in patients with high-risk operable or locally advanced breast cancer. Masked role for assessor.
Only for those patients randomized for the supportive anemia treatment: frequency of patients reaching hemoglobin (Hb) levels ≥ 11g/dl 6 weeks after treatment start of a first episode of anemia grade ≥2
Time frame: 18 weeks (time window + 3 weeks)
Only for those patients randomized for the supportive anemia treatment: To compare the frequency of patients reaching hemoglobin (Hb) levels ≥ 11g/dl 6 weeks after treatment start of a first episode of anemia grade ≥2 (Hb < 10g/dl) between patients receiving supportive treatment for iron deficiency with parental ferric carboxymaltose versus physician's choice (no supportive treatment, oral iron substitution, erythropoiesis-stimulating agent (ESA), or both).
20 secondary outcomes
pcR rates per arm
Time frame: 18 weeks (time frame + 3 weeks)
Clinical and imaging response
Time frame: 18 weeks (time window + 3 weeks)
Rates of ypT0 ypN0; ypT0 ypN0/+; ypT0/is ypN0/+; ypT(any) ypN0; and the residual cancer burden (RCB) score.
Time frame: 18 weeks (time frame + 3 weeks)
Toxicity and Compliance including incidence of febrile neutropenia
Time frame: 18 weeks (time frame + 3 weeks)
Breast conservation rate
Time frame: 18 weeks (time frame: + 3 weeks)
loco-regional invasive recurrence free survival (LRRFS) in both arms and according to stratified subpopulations
Time frame: 5 years
distant-disease-free survival (DDFS) in both arms and according to stratified subpopulations.
Time frame: 5 years
invasive disease-free survival (IDFS) in both arms and according to stratified subpopulations.
Time frame: 5 years
overall survival (OS) in both arms and according to stratified subpopulations.
Time frame: 5 years
regional recurrence free survival (RRFS) in patients with initial node-positive axilla
Time frame: until event occurs - no event for cured patients
pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy
Time frame: 5 years
Correlation of response
Time frame: 18 weeks (time frame + 3 weeks)
Examination and comparison of molecular markers
Time frame: Baseline and 18 weeks (time frame + 3 weeks)
Examination of PIK3CA mutation
Time frame: Baseline and 18 weeks (time frame + 3 weeks)
Only for those patients randomized for the supportive anemia treatment: Quality of life
Time frame: up to 18 weeks
Only for those patients randomized for the supportive anemia treatment: median time to achieve a hemoglobin level ≥11g/dl
Time frame: up to 18 weeks
Only for those patients randomized for the supportive anemia treatment: frequency of patients with a hemoglobin level ≥11g/dl
Time frame: up to 18 weeks
Pharmacogenetic substudy
Time frame: 18 weeks (time frame + 3 weeks)
GeparPET substudy
Time frame: 18 weeks (time frame + 3 weeks)
Ovarian function
Time frame: Baseline until 2 years after EOS
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2017.
- Derived from this study: PubMed 34801353Schneeweiss A, Michel LL, Mobus V, Tesch H, Klare P, Hahnen E, Denkert C, Kast K, Pohl-Rescigno E, Hanusch C, Link T, Untch M, Jackisch C, Blohmer JU, Fasching PA, Solbach C, Schmutzler RK, Huober J, Rhiem K, Nekljudova V, Lubbe K, Loibl S; GBG and AGO-B. Survival analysis of the randomised phase III GeparOcto trial comparing neoadjuvant chemotherapy of intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for patients with high-risk early breast cancer. Eur J Cancer. 2022 Jan;160:100-111. doi: 10.1016/j.ejca.2021.10.011. Epub 2021 Nov 17.
- Derived from this study: PubMed 34252375Denkert C, Seither F, Schneeweiss A, Link T, Blohmer JU, Just M, Wimberger P, Forberger A, Tesch H, Jackisch C, Schmatloch S, Reinisch M, Solomayer EF, Schmitt WD, Hanusch C, Fasching PA, Lubbe K, Solbach C, Huober J, Rhiem K, Marme F, Reimer T, Schmidt M, Sinn BV, Janni W, Stickeler E, Michel L, Stotzer O, Hahnen E, Furlanetto J, Seiler S, Nekljudova V, Untch M, Loibl S. Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials. Lancet Oncol. 2021 Aug;22(8):1151-1161. doi: 10.1016/S1470-2045(21)00301-6. Epub 2021 Jul 9.
- Derived from this study: PubMed 33191846Ruger AM, Schneeweiss A, Seiler S, Tesch H, van Mackelenbergh M, Marme F, Lubbe K, Sinn B, Karn T, Stickeler E, Muller V, Schem C, Denkert C, Fasching PA, Nekljudova V, Garfias-Macedo T, Hasenfuss G, Haverkamp W, Loibl S, von Haehling S. Cardiotoxicity and Cardiovascular Biomarkers in Patients With Breast Cancer: Data From the GeparOcto-GBG 84 Trial. J Am Heart Assoc. 2020 Dec;9(23):e018143. doi: 10.1161/JAHA.120.018143. Epub 2020 Nov 16.
- Derived from this study: PubMed 32163106Pohl-Rescigno E, Hauke J, Loibl S, Mobus V, Denkert C, Fasching PA, Kayali M, Ernst C, Weber-Lassalle N, Hanusch C, Tesch H, Muller V, Altmuller J, Thiele H, Untch M, Lubbe K, Nurnberg P, Rhiem K, Furlanetto J, Lederer B, Jackisch C, Nekljudova V, Schmutzler RK, Schneeweiss A, Hahnen E. Association of Germline Variant Status With Therapy Response in High-risk Early-Stage Breast Cancer: A Secondary Analysis of the GeparOcto Randomized Clinical Trial. JAMA Oncol. 2020 May 1;6(5):744-748. doi: 10.1001/jamaoncol.2020.0007.
- Derived from this study: PubMed 30528802Schneeweiss A, Mobus V, Tesch H, Hanusch C, Denkert C, Lubbe K, Huober J, Klare P, Kummel S, Untch M, Kast K, Jackisch C, Thomalla J, Ingold-Heppner B, Blohmer JU, Rezai M, Frank M, Engels K, Rhiem K, Fasching PA, Nekljudova V, von Minckwitz G, Loibl S. Intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto-GBG 84): A randomised phase III trial. Eur J Cancer. 2019 Jan;106:181-192. doi: 10.1016/j.ejca.2018.10.015. Epub 2018 Dec 5.
Related trials for Tubular Breast Cancer Stage II
Active, not recruitingPhase 2
Combination Chemotherapy With or Without Trastuzumab in Treating Patients With Stage II or Stage III Breast Cancer
Breast Cancer
Active, not recruitingPhase 3
Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
Ductal Breast Carcinoma, Invasive Breast Carcinoma
Active, not recruitingPhase 2
Radiation Therapy in Treating Women With Early Stage Breast Cancer
Breast Cancer
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.
Andreas Schneeweiss, MD, Prof. principal investigator
NTC Heidelberg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing non-pegylated liposomal doxorubicin, Carboplatin and Paclitaxel in people with Tubular Breast Cancer Stage II and Tubular Breast Cancer Stage III, run by GBG Forschungs GmbH at 1 site in Germany.
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 20 inclusion and 24 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: finished, as of the sponsor's last update on 13 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
pathological complete response (pCR= ypT0/is ypN0) (time frame: 18 weeks (time window + 3 weeks)). The study lists 2 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 NCT02125344, which also lists 5 linked publications.
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 13 Jul 2017.