Dual Epidermal Growth Factor Receptor Inhibition With Erlotinib and Panitumumab With or Without Chemotherapy for Advanced Colorectal Cancer

OBJECTIVES:

Primary

• Determine the response rate in patients with metastatic colorectal cancer treated with erlotinib hydrochloride and panitumumab with versus without irinotecan hydrochloride as second-line therapy .

Secondary

• Determine time to disease progression and time to treatment failure in patients treated with these regimens.
• Determine the safety of these regimens in these patients.
• Determine the effect of these regimens on downstream targets of EGFR in skin rash associated with pharmacologic EGFR inhibition (exploratory).
• Determine the association between KRAS mutations and response to EGFR inhibition (exploratory).

OUTLINE: This is a multicenter study. Patients are stratified according to wild-type Kras tumors ( 6/6 UGT1A1 vs 6/7 UGT1A1), and are randomized to 1 of 2 treatment arms. Patients with wild-type Kras tumor 7/7 UGT1A1 receive treatment in arm III.

• Arm I: Patients receive oral erlotinib hydrochloride once daily on days 1-14, panitumumab IV over 30-90 minutes on day 1, and irinotecan hydrochloride IV over 90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive oral erlotinib hydrochloride once daily on days 1-14 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Upon disease progression, patients receive irinotecan hydrochloride as in arm I.
• Arm III: Patients receive erlotinib hydrochloride and panitumumab as in arm II. Skin biopsies and blood samples may be collected for further analysis.

After completion of study therapy, patients are followed every 6 weeks.

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer

• Metastatic disease

• Biopsy of either the primary cancer or metastatic site required
• Tumor expressing wild-type Kras mutations
• Progressive disease within 3 months after treatment with first-line fluorouracil (5-FU) and oxaliplatin-based chemotherapy OR evidence of metastatic disease within 6 months of completing adjuvant therapy with 5-FU and oxaliplatin
• Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques OR as ≥ 10 mm with spiral CT scan

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 6 months
• ANC > 1,500/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin ≥ 9 g/dL
• Creatinine < 1.5 times upper limit of normal (ULN)
• Bilirubin < 1.5 times ULN (or < 2 mg/dL)
• AST and/or ALT < 3 times ULN (< 5 times ULN with liver metastases)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent malignancy requiring therapy except minor surgery for non-melanoma skin cancer removal
• No interstitial lung disease with symptoms (e.g., dyspnea or cough) including any of the following significant conditions:

• Parenchymal lung disease
• Metastatic disease
• Pulmonary infections

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior EGFR inhibitors, irinotecan hydrochloride, or other second-line chemotherapy regimens
• More than 4 weeks since prior radiotherapy
• No other concurrent investigational agents
• No other concurrent anticancer treatment modalities (e.g., radiotherapy)