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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Genentech
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00821886
First received: January 12, 2009
Last updated: November 15, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Ixabepilone
Drug: Trastuzumab
Drug: Carboplatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Neoadjuvant Ixabepilone/Carboplatin/Trastuzumab in HER2-Positive Locally Advanced Breast Cancer

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • complete response rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To estimate the pathologic complete response rate of the combination of ixabepilone/carboplatin/trastuzumab as neoadjuvant therapy


Secondary Outcome Measures:
  • Number of subjects with Adverse Events as a measure of safety and toxicity [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    To determine the safety and toxicity of the combination of ixabepilone/carboplatin/trastuzumab as neoadjuvant treatment

  • Disease-free survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To determine the disease-free survival (DFS) with this treatment combination

  • Overall Survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To determine the overall survival (OS) with this treatment combination


Enrollment: 60
Study Start Date: February 2009
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ixabepilone/Trastuzumab/Carboplatin
Neoadjuvant Treatment, followed by surgery, peri-operative treatment and post-operative (adjuvant) treatment if patient deemed to be a surgical candidate
Drug: Ixabepilone
Ixabepilone 40mg/m2 IV infusion over 3 hours on day 1 of cycles 1-6 (all treatment cycles are 21 days in length)
Other Names:
  • Ixempra
  • BMS-247550
  • NCS 710248
  • Neoadjuvant Treatment
Drug: Trastuzumab
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
Other Names:
  • Herceptin
  • Neoadjuvant Therapy
Drug: Carboplatin
Carboplatin AUC=6 IV per institutional guidelines on Day 1 of Cycles 1-6 (all treatment cycles are 21 days in length)
Other Names:
  • Paraplatin
  • Neoadjuvant Therapy

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Female and male patients ≥18 years of age.
  2. Histologically confirmed adenocarcinoma of the breast.
  3. 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.)
  4. 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.
  5. 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.
  6. An ECOG (Eastern Cooperative Oncology Group) performance score of ≤2
  7. Normal bone marrow function as defined by:

    • absolute neutrophil count (ANC) >1,500/µL;
    • platelets >100,000/µL;
    • hemoglobin >10 g/dL.
  8. Normal hepatic function as defined by:

    • total bilirubin within normal institutional limits;
    • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 × the institutional upper limit of normal (ULN).
  9. Normal renal function as defined by creatinine ≤1.5 × ULN or estimated creatinine clearance (CrCl) ≥50 mL/min calculated by the Cockcroft-Gault method.
  10. 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).
  11. Life expectancy > 12 weeks.
  12. Estrogen and progesterone (or estrogen alone) receptor status in the primary tumor known or pending at the time of study enrollment.
  13. For women of childbearing potential, negative serum pregnancy test within 7 days prior to starting treatment.
  14. 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.
  15. 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.
  16. 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.
  17. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Previous treatment for this breast cancer.
  2. Evidence of metastatic disease.
  3. Prior radiation that included ≥30% of major bone marrow-containing areas.
  4. Women who are pregnant or breastfeeding.
  5. Neuropathy (motor or sensory) ≥grade 1 at study entry.
  6. 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.
  7. Symptomatic intrinsic lung disease.
  8. 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.
  9. Uncontrolled intercurrent illness including (but not limited to) ongoing or active infection >grade 2.
  10. 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.
  11. 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.
  12. 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.
  13. Received chemotherapy for any indication within the 5 years preceding study enrollment.
  14. Prior treatment with trastuzumab or any other anti-HER2 agent for any indication.
  15. Concurrent treatment with any other anti-cancer therapy.
  16. Concurrent radiation therapy during neoadjuvant study treatment.
  17. Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment must be stopped prior to study enrollment.
  18. 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.
  19. Participation within the previous 30 days in a study with an experimental drug.
  20. 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.
  21. Inability or unwillingness to comply with study procedures including those for follow-up.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00821886

Locations
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
United States, Georgia
Medical Oncology Associates of Augusta
Augusta, Georgia, United States, 30901
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Indiana
Providence Medical Group
Terre Haute, Indiana, United States, 47802
United States, Maine
Mercy Hospital
Portland, Maine, United States, 04101
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
National Capital Clinical Research Consortium
Bethesda, Maryland, United States, 20817
United States, Michigan
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Missouri
St. Louis Cancer Care
Chesterfield, Missouri, United States, 63017
United States, New Jersey
Hematology Oncology Associates of Northern NJ
Morristown, New Jersey, United States, 07960
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
United States, South Carolina
South Carolina Oncology Associates, PA
Columbia, South Carolina, United States, 29210
United States, Tennessee
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
United States, Virginia
Virginia Cancer Institute
Richmond, Virginia, United States, 23235
Sponsors and Collaborators
SCRI Development Innovations, LLC
Bristol-Myers Squibb
Genentech
Investigators
Study Chair: Denise Yardley, M.D. SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00821886     History of Changes
Other Study ID Numbers: SCRI BRE 139
Study First Received: January 12, 2009
Last Updated: November 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Breast Cancer
Neoadjuvant
Ixabepilone
Carboplatin
Trastuzumab

Additional relevant MeSH terms:
Trastuzumab
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carboplatin
Epothilones
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014