Pertuzumab and Cetuximab in Treating Patients With Previously Treated Locally Advanced or Metastatic Colorectal Cancer

Inclusion Criteria

• Patients with a history of colorectal cancer (CRC) treated by surgical resection and who develop radiological or clinical evidence of metastatic disease do not require separate histological or cytological confirmation of metastatic disease unless 1 of the following criteria are met:
• More than 5 years has elapsed between the primary surgery and the development of metastatic disease
• The primary cancer was stage I
• Patients must have representative tumor specimens in paraffin blocks or at least 15 unstained slides with an associated pathology report obtained at any time prior to study entry:
• Cytology specimens are not acceptable replacements
• Patients must have their tumor tissue screened for KRAS mutation status, and be found to have a KRAS wild-type tumor:
• No KRAS-mutated tumor
• Locally advanced or metastatic disease
• Not curable by surgery or amenable to radiotherapy with curative intent
• Must have received an cetuximab-containing regimen for at least 6 weeks for treatment of metastatic disease
• Documented progression of disease or intolerable toxicity during or within 3 months of receiving this regimen
• Patients who have received an cetuximab-containing regimen as adjuvant therapy for resected stage II or III CRC are eligible provided recurrent disease is documented = 1 prior chemotherapeutic regimen for treatment of metastatic disease with any of the following:
• Cetuximab
• Must have resolution of any skin rash related to prior treatment with cetuximab
• No prior cetuximab which required a dose reduction for toxicity
• 5-fluorouracil or capecitabine
• Irinotecan hydrochloride or oxaliplatin
• Measurable disease by CT scan or physical exam
• ECOG performance status (PS) 0-1 (Karnofsky PS 70-100%)
• Life expectancy > 12 weeks
• Absolute neutrophil count >= 1,500/mcL
• Platelet count >= 100,000/mcL
• Leukocytes >= 3,000/mcL
• Hemoglobin >= 9 g/dL (transfusion, erythropoietin, or other approved hematopoietic growth factors allowed)
• Total bilirubin = = 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception prior to and during study therapy
• Cardiac left ventricular ejection fraction >= 50% OR >= lower limit of normal
• No evidence of left ventricular wall motion abnormalities as measured by ECHO or MUGA scan
• None of the following cardiac conditions:
• Uncontrolled high blood pressure
• Unstable angina
• Symptomatic congestive heart failure
• Congestive heart failure, cardiac dysfunction, or cardiomyopathy requiring medication treatment
• Myocardial infarction within the past 6 months
• Serious uncontrolled cardiac arrhythmia
• New York Heart Association class III or IV heart disease
• No active or uncontrolled infection
• No predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline pattern of > 3 loose stools/day (in patients without a colostomy or ileostomy)
• Patients with a colostomy or ileostomy may be eligible at investigator discretion
• No psychiatric illness/social situation that would limit compliance with study requirements
• No other prior or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ carcinoma of the cervix, lobular carcinoma in situ in one breast, or other cancer from which the patient has been disease-free for at least 5 years
• No other medical or psychiatric disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the study results or render the patient at high risk for treatment complications
• No history of allergic reactions, hypersensitivity, or intolerance to cetuximab, and/or compounds of similar chemical or biologic composition to pertuzumab or cetuximab (i.e., other monoclonal antibodies such as bevacizumab)