Breast CancerPhase 2NCT00821886
Neoadjuvant Ixabepilone/Carboplatin/Trastuzumab in HER2-Positive Locally Advanced Breast Cancer
A Phase 2 study testing Ixabepilone, Trastuzumab and Carboplatin in people with Breast Cancer, run by SCRI Development Innovations, LLC at 12 sites in United States.
Trial summary
In this phase II trial the investigators propose to evaluate ixabepilone in combination with carboplatin and trastuzumab as neoadjuvant therapy in locally advanced breast cancer patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Ixabepilone, Trastuzumab and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 12 sitesUnited States
- Study dates
- Feb 2009to Oct 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
- Female and male patients ≥18 years of age.
- Histologically confirmed adenocarcinoma of the breast.
- Primary palpable disease confined to a breast and axilla on physical examination. For patients without clinically suspicious axillary adenopathy, the primary tumor must be larger than 2 cm in diameter (clinical T2-T3, N0-N1, M0). For patients with clinically suspicious axillary adenopathy, the primary breast tumor can be any size (clinical T1-T3, N1-N2, M0). (T1N0M0 lesions are excluded.)
- Patients who have no clearly defined palpable breast mass or axillary lymph nodes but are radiographically measurable are eligible. Accepted procedures for measuring breast disease are mammography, MRI, and breast ultrasound. In these patients, radiographic tumor measurements need to be repeated after 3 cycles and prior to surgery.
- Positive HER2 status (overexpression and/or amplification of HER2 in the primary tumor) as defined by: IHC 3+ or fluorescence in situ hybridization (FISH) positive (ratio >2.2) testing. Documentation of the HER2 results must be available at the time of study enrollment.
- An ECOG (Eastern Cooperative Oncology Group) performance score of ≤2
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- Normal bone marrow function as defined by:
- absolute neutrophil count (ANC) >1,500/µL;
- platelets >100,000/µL;
- hemoglobin >10 g/dL.
- Normal hepatic and renal function.
- Left ventricular ejection fraction (LVEF) within the institutional limits of normal, whichever is lower, as measured by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO).
- Life expectancy > 12 weeks.
- Estrogen and progesterone (or estrogen alone) receptor status in the primary tumor known or pending at the time of study enrollment.
- For women of childbearing potential, negative serum pregnancy test within 7 days prior to starting treatment.
- For women of childbearing potential, agreement to use a method of contraception that is acceptable to their physician from time of first signing the informed consent until at least 3 months after the last dose of study drug. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately. Patient agreement to discontinue breast-feeding, if applicable, during study treatment. Men enrolled in the study must also agree to use a method of contraception that is acceptable to their physician during their study participation.
- For patients with previous invasive cancers (including breast cancer) treated with curative intent, completion of chemotherapy or radiation therapy more than 5 years prior to enrollment for this study and no evidence of recurrent disease. Patients may be receiving anti-estrogen hormonal therapy prescribed for previous invasive breast cancer as long as the diagnosis of invasive cancer was made more than 5 years prior to study enrollment. Patients may be using anti-estrogen hormonal therapy at the time of current diagnosis but must discontinue this therapy before beginning study treatment.
- For patients who had, or will have sentinel lymph node and/or axillary dissection prior to initiation of study treatment, completion at least 4 weeks prior to starting study treatment and well-healed wound.
- Ability to understand and willingness to sign a written informed consent document.
Who cannot join
- Previous treatment for this breast cancer.
- Evidence of metastatic disease.
- Prior radiation that included ≥30% of major bone marrow-containing areas.
- Women who are pregnant or breastfeeding.
- Neuropathy (motor or sensory) ≥grade 1 at study entry.
- History of significant cardiac disease or cardiac risk factors or the following:
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- uncontrolled arrhythmias
- poorly controlled hypertension (e.g., systolic blood pressure [BP]> 150 mmHg or diastolic BP >100 mmHg) in spite of optimal medical management
- angina pectoris requiring antianginal medication or unstable angina within the previous 6 months
- history of documented congestive heart failure (CHF)
- any documented myocardial infarction within the previous 6 months
- clinically significant valvular heart disease
- current use of medications (e.g., digitalis, beta-blockers, calcium channel-blockers) that alter cardiac conduction, if these medications are administered for the management of cardiac arrhythmia, angina, or CHF. If these medications are administered for other reasons (e.g., hypertension), the patient may be eligible.
- patients with cardiomegaly on chest x-ray or ventricular hypertrophy on ECG unless ECHO or MUGA scan within the last 3 months demonstrates that the LVEF is ≥ institutional lower limit of normal.
- Symptomatic intrinsic lung disease.
- Active malignancy, other than superficial basal cell carcinoma, superficial squamous (skin) cell carcinoma, carcinoma in situ, or non-invasive breast cancer, within the past 5 years.
- Uncontrolled intercurrent illness including (but not limited to) ongoing or active infection >grade 2.
- Mental condition or psychiatric disorder rendering the subject unable to understand the nature, scope, and possible consequences of the study or that would limit compliance with study requirements.
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving a reasonable suspicion of a disease or condition that contraindicates the use of a study agent or that may affect the interpretation of the results or renders the subjects at high risk from treatment complications.
- Chronic use of CYP3A4 inhibitors and use of the following strong CYP3A4 inhibitors: ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine, and voriconazole. Use of these agents must be discontinued at least 72 hours prior to initiation of study treatment.
- Received chemotherapy for any indication within the 5 years preceding study enrollment.
- Prior treatment with trastuzumab or any other anti-HER2 agent for any indication.
- Concurrent treatment with any other anti-cancer therapy.
- Concurrent radiation therapy during neoadjuvant study treatment.
- Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment must be stopped prior to study enrollment.
- Current therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or prevention of breast cancer. These agents must be discontinued prior to study enrollment.
- Participation within the previous 30 days in a study with an experimental drug.
- Known or suspected allergy to Cremophor EL (polyoxyethylated castor oil), a drug formulated in Cremophor EL such as paclitaxel, or any other agent given in the course of this trial.
- Inability or unwillingness to comply with study procedures including those for follow-up.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Medical Oncology Associates of Augusta
Augusta, Georgia, 30901
Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817
National Capital Clinical Research Consortium
Bethesda, Maryland, 20817
St. Louis Cancer Care
Chesterfield, Missouri, 63017
Oncology Hematology Care
Cincinnati, Ohio, 45242
Florida Cancer Specialists
Fort Myers, Florida, 33901
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, 49503
Hematology Oncology Associates of Northern NJ
Morristown, New Jersey, 07960
Tennessee Oncology, PLLC
Nashville, Tennessee, 37023
Mercy Hospital
Portland, Maine, 04101
Virginia Cancer Institute
Richmond, Virginia, 23235
Providence Medical Group
Terre Haute, Indiana, 47802
About this study
Official title: Phase II Study of Neoadjuvant Ixabepilone/Carboplatin/Trastuzumab in HER2-Positive Locally Advanced Breast Cancer
In this phase II trial the investigators propose to evaluate ixabepilone in combination with carboplatin and trastuzumab as neoadjuvant therapy in locally advanced breast cancer patients. Patients with early stage, HER2-positive breast cancer will receive six cycles of neoadjuvant treatment with ixabepilone, carboplatin, and trastuzumab every three weeks prior to surgery; after surgery, patients will continue treatment with trastuzumab every three weeks until week 52. Concomitant with the post-operative trastuzumab treatment, patients with hormone receptor-positive tumors will receive anti-estrogen treatment. Also, after the completion of chemotherapy, patients may receive radiation treatment at the discretion of their physician.
- Conditions
- Breast Cancer
- Being tested
- Ixabepilone, Trastuzumab, Carboplatin
- Keywords
- Breast Cancer, Neoadjuvant, Ixabepilone, Carboplatin, Trastuzumab
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IxabepiloneDrug
Also called Ixempra, BMS-247550, NCS 710248, Neoadjuvant Treatment
Ixabepilone 40mg/m2 IV infusion over 3 hours on day 1 of cycles 1-6 (all treatment cycles are 21 days in length)
TrastuzumabDrug
Also called Herceptin, Neoadjuvant Therapy
Trastuzumab 8mg/kg IV over 90 minutes for the first infusion (Cycle 1, Day 1) with a 60 minute post-infusion observation period. Subsequent infusions (Day 1 of Cycles 2-6 with all cycles being 21 days in length) 6mg/kg over 30 minutes if the previous dose was well tolerated; peri-operative trastuzumab 6mg/kg IV every 3-4 weeks; post-operative trastuzumab 6mg/kg IV day 1 every 3 weeks until week 52
CarboplatinDrug
Also called Paraplatin, Neoadjuvant Therapy
Carboplatin AUC=6 IV per institutional guidelines on Day 1 of Cycles 1-6 (all treatment cycles are 21 days in length)
| Study group | Role | What they receive |
|---|---|---|
| Ixabepilone/Trastuzumab/Carboplatin | Experimental | Neoadjuvant treatment with Ixabepilone, Trastuzumab and Carboplatin, followed by surgery, peri-operative treatment and post-operative (adjuvant) treatment if patient deemed to be a surgical candidate Receives: Drug: Ixabepilone; Drug: Trastuzumab; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response (pCR)
Proportion of patients who do not exhibit residual invasive breast cancer in breast or axillary lymph nodes at time of surgery
Measured: average18 months
Secondary outcomes (3)
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Assessment based on the frequency of treatment-related adverse events according to NCI CTCAE criteria v3.0.
Measured: Day 1 of each 3 week cycle up to 6 cycles , and every 9 weeks post-surgery until treatment discontinuation
Disease-free Survival
Defined as the interval from the first date of study treatment until the date of tumor recurrence or death from any cause
Measured: expected average 18 months
Overall Survival
Defined as the time between Day 1 Cycle 1 to date of death from any cause.
Measured: approximately 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2009 (estimated)
- Study startFeb 2009
- Primary completionJul 2011
- Study completionOct 2014
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.
- Other trials for Breast CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Denise Yardley, M.D., Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00821886
- Sponsor's protocol ID
- SCRI BRE 139
- Status last verified
- Dec 2014
- First submitted
- 12 Jan 2009
- Last updated
- 22 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Neoadjuvant Ixabepilone/Carboplatin/Trastuzumab in HER2-Positive Locally Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT00821886
- Acronym / sponsor ID
- SCRI BRE 139
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer, Neoadjuvant, Ixabepilone, Carboplatin, Trastuzumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Genentech, Inc.
- Study start
- Feb 2009
- Primary completion
- Jul 2011 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 14 Jan 2009 (estimated)
- Results
- Posted 22 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this phase II trial the investigators propose to evaluate ixabepilone in combination with carboplatin and trastuzumab as neoadjuvant therapy in locally advanced breast cancer patients. Patients with early stage, HER2-positive breast cancer will receive six cycles of neoadjuvant treatment with ixabepilone, carboplatin, and trastuzumab every three weeks prior to surgery; after surgery, patients will continue treatment with trastuzumab every three weeks until week 52. Concomitant with the post-operative trastuzumab treatment, patients with hormone receptor-positive tumors will receive anti-estrogen treatment. Also, after the completion of chemotherapy, patients may receive radiation treatment at the discretion of their physician.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ixabepilone/Trastuzumab/Carboplatin | Experimental | Drug: Ixabepilone, Drug: Trastuzumab, Drug: CarboplatinNeoadjuvant treatment with Ixabepilone, Trastuzumab and Carboplatin, followed by surgery, peri-operative treatment and post-operative (adjuvant) treatment if patient deemed to be a surgical candidate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Female and male patients ≥18 years of age.
- Histologically confirmed adenocarcinoma of the breast.
- Primary palpable disease confined to a breast and axilla on physical examination. For patients without clinically suspicious axillary adenopathy, the primary tumor must be larger than 2 cm in diameter (clinical T2-T3, N0-N1, M0). For patients with clinically suspicious axillary adenopathy, the primary breast tumor can be any size (clinical T1-T3, N1-N2, M0). (T1N0M0 lesions are excluded.)
- Patients who have no clearly defined palpable breast mass or axillary lymph nodes but are radiographically measurable are eligible. Accepted procedures for measuring breast disease are mammography, MRI, and breast ultrasound. In these patients, radiographic tumor measurements need to be repeated after 3 cycles and prior to surgery.
- Positive HER2 status (overexpression and/or amplification of HER2 in the primary tumor) as defined by: IHC 3+ or fluorescence in situ hybridization (FISH) positive (ratio >2.2) testing. Documentation of the HER2 results must be available at the time of study enrollment.
Key exclusion criteria (29 listed)
- Previous treatment for this breast cancer.
- Evidence of metastatic disease.
- Prior radiation that included ≥30% of major bone marrow-containing areas.
- Women who are pregnant or breastfeeding.
- Neuropathy (motor or sensory) ≥grade 1 at study entry.
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 |
|---|---|---|
| IxabepiloneAlso: Ixempra, BMS-247550, NCS 710248, Neoadjuvant TreatmentIxabepilone 40mg/m2 IV infusion over 3 hours on day 1 of cycles 1-6 (all treatment cycles are 21 days in length) | Drug | Ixabepilone/Trastuzumab/Carboplatin |
| TrastuzumabAlso: Herceptin, Neoadjuvant TherapyTrastuzumab 8mg/kg IV over 90 minutes for the first infusion (Cycle 1, Day 1) with a 60 minute post-infusion observation period. Subsequent infusions (Day 1 of Cycles 2-6 with all cycles being 21 days in length) 6mg/kg over 30 minutes if the previous dose was well tolerated; peri-operative trastuzumab 6mg/kg IV every 3-4 weeks; post-operative trastuzumab 6mg/kg IV day 1 every 3 weeks until week 52 | Drug | Ixabepilone/Trastuzumab/Carboplatin |
| CarboplatinAlso: Paraplatin, Neoadjuvant TherapyCarboplatin AUC=6 IV per institutional guidelines on Day 1 of Cycles 1-6 (all treatment cycles are 21 days in length) | Drug | Ixabepilone/Trastuzumab/Carboplatin |
Primary outcome
Pathologic Complete Response (pCR)
Time frame: average18 months
Proportion of patients who do not exhibit residual invasive breast cancer in breast or axillary lymph nodes at time of surgery
3 secondary outcomes
Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
Time frame: Day 1 of each 3 week cycle up to 6 cycles , and every 9 weeks post-surgery until treatment discontinuation
Disease-free Survival
Time frame: expected average 18 months
Overall Survival
Time frame: approximately 48 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Denise Yardley, M.D. study chair
SCRI Development Innovations, LLC
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ixabepilone, Trastuzumab and Carboplatin in people with Breast Cancer, run by SCRI Development Innovations, LLC at 12 sites in United States.
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 19 inclusion and 29 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 22 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. 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 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 22 Dec 2014). 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?
Pathologic Complete Response (pCR) (time frame: average18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Dec 2014.