- To evaluate the progression-free survival of patients with advanced K-ras wild-type colorectal cancer, following progression on bevacizumab-contained chemotherapy, treated with irinotecan hydrochloride and cetuximab with versus without ramucirumab as second-line therapy.
- To evaluate the response rate in patients treated with these regimens.
- To evaluate the grade 3-4 toxicity rates of these regimens in these patients.
- To evaluate the overall suvival of patients treated with these regimens.
OUTLINE: This is a multicenter, randomized study. Patients are stratified according to performance status (0 vs 1), discontinuation of oxaliplatin before disease progression (yes vs no), and time to disease progression since last treatment (≤ 6 months vs > 6 months). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride over 60-90 minutes on day 1.
- Arm II: Patients receive ramucirumab IV over 60 minutes on day 1 and cetuximab and irinotecan hydrochloride as in arm I.
In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up periodically for 5 years.
- 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
- 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
|Maximum Eligible Age:||N/A|
|Minimum Eligible Age:||18 Years|