Irinotecan and Cetuximab in Treating Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving irinotecan together with cetuximab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving irinotecan together with cetuximab works in treating patients with metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the antitumor activity, by confirmed response rate, of concurrent irinotecan hydrochloride and cetuximab in patients with metastatic breast cancer with prior anthracycline and/or taxane-containing therapy. Secondary Estimate 6-month, progression-free survival of patients. Evaluate the adverse event profile of irinotecan hydrochloride in combination with cetuximab in patients with metastatic breast cancer. Estimate progression-free survival of patients. Estimate overall survival. OUTLINE: Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and irinotecan hydrochloride IV over 1½ hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 5 years. PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study.

Official Title
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Phase II Trial of Concurrent Irinotecan Plus Cetuximab in Patients With Advanced Breast Cancer With Prior Anthracycline and/or Taxane-Containing Therapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the breast Clinical manifestations of metastatic disease If patient's tumor is HER2 positive (3+ by immunohistochemistry [IHC] or amplified by fluorescent in situ hybridization [FISH]), must have received at least one prior trastuzumab (Herceptin)-containing regimen unless there is a contraindication Measurable disease defined as at least one lesion whose longest diameter can be accurately measured The only evidence of metastasis must not be bone metastases or other non-measurable disease Nonmeasurable disease is defined as all other lesions, including small lesions (longest diameter < 2 cm) and truly nonmeasurable lesions which include any of the following: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Inflammatory breast disease Lymphangitis cutis/pulmonis Cystic lesions Abdominal masses that are not confirmed and followed by imaging techniques No known CNS metastasis unless controlled by prior surgery and/or radiotherapy To be considered controlled, there must be at least 2 months of no symptoms or evidence of progression prior to study entry Hormone receptor status Not specified PATIENT CHARACTERISTICS: Men or women Menopausal status not specified ECOG performance status 0-2 Life expectancy > 3 months Hemoglobin > 8.0 g/dL Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Creatinine ≤ 1.5 times upper limit of normal (ULN) Bilirubin normal AST and ALT ≤ 5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must employ adequate contraception (as determined by the treating physician) during treatment and for 30 days after treatment ends Disease-free for ≥ 3 years of other invasive non-breast malignancies (exception: curatively treated basal cell or squamous cell carcinoma of the skin and carcinoma in situ of the cervix) No history of allergy or hypersensitivity to drug product excipients, murine antibodies, or agents chemically similar to irinotecan and/or cetuximab No history or evidence of Gilbert's syndrome No active, unresolved infection No New York Heart Association class III or IV cardiovascular disease No serious concomitant medical condition that would make it undesirable for patient to participate in the trial or would jeopardize compliance with protocol treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics No more than 2 prior chemotherapy regimens in the metastatic setting (irrespective of hormonal therapy or prior trastuzumab therapy) Prior treatment in the metastatic or adjuvant setting must have included an anthracycline or a taxane No major surgery ≤ 3 weeks prior to registration No chemotherapy ≤ 2 weeks prior to registration No radiotherapy ≤ 4 weeks prior to registration No prior irinotecan hydrochloride No prior therapy with an epidermal growth factor receptor (EGFR) antagonist (either monoclonal antibody or tyrosine kinase inhibitor), such as gefitinib or erlotinib No prior therapy with a dual EGFR/HER2 inhibitor (e.g., lapatinib) No concurrent interleukin-11(oprelvekin) Routine use of granulocyte colony stimulating factors (CSFs) is not permitted during course 1 of this study Subsequent use of CSFs is permitted at the discretion of the treating investigator No other concurrent antitumor therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cetuximab + irinotecan<br>Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and irinotecan hydrochloride IV over 1½ hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 5 years. | Biological: cetuximab<br> <br> Drug: irinotecan hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed tumor response (complete or partial) |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease progression |  | Up to 5 years | 
| Survival time |  | Up to 5 years | 
| Progression-free survival at 6 months |  | at 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IV breast cancer, male breast cancer