A Randomized Phase II Study of Irinotecan and Cetuximab With or Without the Anti-Angiogenic Antibody, Ramucirumab (IMC-1121B), in Advanced, K-ras Wild-Type Colorectal Cancer Following Progression on Bevacizumab-Containing Chemotherapy

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the colon or rectum, including:

- Advanced disease

- Histologic variants of adenocarcinoma allowed

- K-ras wild type based on either primary or metastatic tumor

- No mutated type

- Measurable disease

- Must have received prior first-line therapy comprising oxaliplatin-based
fluoropyrimidine-containing chemotherapy and bevacizumab for metastatic colorectal
cancer

- No more than 42 days since confirmed disease progression

- No brain or CNS metastases

PATIENT CHARACTERISTICS:

- Performance status 0-1

- ANC ≥ 1,500/μL

- Platelet count ≥ 75,000/μL

- Hemoglobin ≥ 9 g/dL

- Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 40
mL/min

- Urine protein ≤ 1+ on dipstick or routine urinalysis (if ≥ 2+, a 24-hour urine
collection must demonstrate < 1,000 mg of protein)

- Total bilirubin ≤ 2.0 mg/dL

- AST and ALT ≤ 3.0 times ULN (5.0 times ULN for patients with liver metastases)

- INR ≤ 1.6 (≤ 3.0 for patients on warfarin and no active bleeding [i.e., no bleeding
within the past 14 days])

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study therapy

- No clinically significant (equivalent to NCI CTCAE grade 3-4) bleeding episodes
within the past 3 months

- None of the following:

- Active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Symptomatic or poorly controlled cardiac arrhythmia

- Uncontrolled thrombotic or hemorrhagic disorder

- No uncontrolled or poorly controlled hypertension despite standard medical management
(e.g., consistently systolic BP > 160 mm Hg and diastolic BP > 90 mm Hg)

- No acute arterial thrombotic events within the past 6 months, including
cerebrovascular accident, transient ischemic attack, myocardial infarction, or
unstable angina

- No other cancer requiring therapy within the past 3 years except in situ carcinoma or
nonmelanoma skin cancer

- No acute or subacute intestinal obstruction

- No history of inflammatory bowel disease requiring pharmacological and/or surgical
intervention within the past 12 months

- No known allergy to any of the treatment components

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 28 days and no more than 90 days since prior bevacizumab

- No prior therapy with drugs other than oxaliplatin and a fluoropyrimidine plus
bevacizumab for colorectal cancer

- No major surgery within the past 28 days

- No subcutaneous venous access device placement within the past 7 days

- Concurrent stable dose of oral anticoagulant or low-molecular weight heparin allowed