Neoadjuvant Ixabepilone/Carboplatin/Trastuzumab in HER2-Positive Locally Advanced Breast Cancer

NCT00821886 | Completed Phase 2 Results

• 1 other identifier: SCRI BRE 139
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 12

Brief 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. 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

Keywords

Breast Cancer; Neoadjuvant; Ixabepilone; Carboplatin; Trastuzumab

Outcome Measures

Primary Outcomes (1)

• 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

  average18 months

Secondary Outcomes (3)

• Number of Subjects With Adverse Events as a Measure of Safety and Toxicity

  Day 1 of each 3 week cycle up to 6 cycles , and every 9 weeks post-surgery until treatment discontinuation

• Disease-free Survival

  expected average 18 months

• Overall Survival

  approximately 48 months

Study Arms (1)

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

Drug: Ixabepilone; Drug: Trastuzumab; Drug: Carboplatin

Interventions

Ixabepilone DRUG

Ixabepilone 40mg/m2 IV infusion over 3 hours on day 1 of cycles 1-6 (all treatment cycles are 21 days in length)

Also known as: Ixempra, BMS-247550, NCS 710248, Neoadjuvant Treatment

Ixabepilone/Trastuzumab/Carboplatin

Trastuzumab DRUG

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

Also known as: Herceptin, Neoadjuvant Therapy

Ixabepilone/Trastuzumab/Carboplatin

Carboplatin DRUG

Carboplatin AUC=6 IV per institutional guidelines on Day 1 of Cycles 1-6 (all treatment cycles are 21 days in length)

Also known as: Paraplatin, Neoadjuvant Therapy

Ixabepilone/Trastuzumab/Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Bristol-Myers Squibb: collaborator
• Genentech, Inc.: collaborator

Study Sites (12)

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Medical Oncology Associates of Augusta

Augusta, Georgia, 30901, United States

Location

Providence Medical Group

Terre Haute, Indiana, 47802, United States

Location

Mercy Hospital

Portland, Maine, 04101, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

National Capital Clinical Research Consortium

Bethesda, Maryland, 20817, United States

Location

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, 49503, United States

Location

St. Louis Cancer Care

Chesterfield, Missouri, 63017, United States

Location

Hematology Oncology Associates of Northern NJ

Morristown, New Jersey, 07960, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23235, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ixabepilone; Neoadjuvant Therapy; Trastuzumab; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: John D. Hainsworth, MD
• Organization: Sarah Cannon Research Institute

asksarah@scresearch.net

1-877-691-7274

Study Officials

• Denise Yardley, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2009
• First Posted: January 14, 2009
• Study Start: February 1, 2009
• Primary Completion: July 1, 2011
• Study Completion: October 1, 2014
• Last Updated: December 22, 2014
• Results First Posted: December 22, 2014

Record last verified: 2014-12

Locations

US (12)