Irinotecan and Cetuximab in Treating Patients With Metastatic Breast Cancer
Irinotecan and Cetuximab in Treating Patients With Metastatic Breast Cancer
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.
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.
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