a study in second line metastatic colorectal cancer

Conditions: Colorectal Cancer

Summary: the purpose of this study is to compare overall survival in participants with metastatic colorectal cancer treated with either ramucirumab and folfiri or placebo and folfiri.


Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed colorectal cancer, excluding primary tumors of appendiceal origin (participants are eligible to enroll irrespective of kras mutation status) * confirmed metastatic colorectal cancer (stage iv) * the participant has received first-line combination therapy of bevacizumab, oxaliplatin, and a fluoropyrimidine for metastatic disease and, a) experienced radiographic disease progression during first-line therapy, or b) experienced radiographic disease progression ≤6 months after the last dose of first-line therapy, or c) discontinued part or all of first-line therapy due to toxicity and experienced radiographic disease progression ≤6 months after the last dose of first-line therapy. note that a participant must have received a minimum of 2 doses of bevacizumab as part of a first-line regimen containing chemotherapy; in addition, a participant must have received at least 1 cycle of first-line therapy that included bevacizumab, oxaliplatin and a fluoropyrimidine in the same cycle. note that a participant must not have received more than 2 different fluoropyrimidines as part of a first-line regimen; disease progression is not an acceptable reason for discontinuing 1 fluoropyrimidine and starting a second fluoropyrimidine * receipt of no more than 2 prior systemic chemotherapy regimens in any setting (only 1 prior regimen for metastatic disease is permitted). for participants with rectal cancer, sequential neoadjuvant and adjuvant therapy will count as a single systemic regimen. note that rechallenge with oxaliplatin is permitted and will be considered part of the first-line regimen for metastatic disease, both initial oxaliplatin treatment and subsequent rechallenge are considered as 1 regimen * measurable or nonmeasurable disease based on the response evaluation criteria in solid tumors, version 1.1 (recist v1.1) * eastern cooperative oncology group (ecog) performance status (ps) of 0 or 1 * adequate hematologic, renal and hepatic function * adequate coagulation function \[international normalized ratio (inr) ≤1.5 and partial thromboplastin time (ptt) or activated ptt (aptt) ≤1.5 x upper limit of normal (uln)). participants on full-dose anticoagulation must be on a stable dose of anticoagulant therapy and if on oral anticoagulation, must have an inr ≤3 and have no clinically significant active bleeding or pathological condition that carries a high risk of bleeding * consent to provide a historical colorectal cancer tissue sample for assessment of biomarkers and the tumor tissue sample is available * ability to provide signed informed consent exclusion criteria: * receipt of bevacizumab ≤28 days prior to randomization * receipt of any investigational therapy for non-oncology clinical indication ≤28 days prior to randomization * receipt of any previous systemic therapy, other than a combination of bevacizumab, oxaliplatin, and a fluoropyrimidine, for first-line treatment of metastatic colorectal cancer * known leptomeningeal disease or brain metastases or uncontrolled spinal cord compression (currently or in the past) * experience of any arterial thrombotic or arterial thromboembolic events, including, but not limited to, myocardial infarction, transient ischemic attack, or cerebrovascular accident, ≤12 months prior to randomization * pregnant (confirmed by serum beta human chorionic gonadotropin (ß hcg) test ≤7 days prior to randomization) or lactating * history of inflammatory bowel disease or crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization * acute or subacute bowel obstruction or history of chronic diarrhea which is considered clinically significant in the opinion of the investigator * grade 3 or higher bleeding event ≤3 months prior to randomization * experience of any of the following during first-line therapy with a bevacizumab-containing regimen: an arterial thrombotic/thromboembolic event, grade 4 hypertension, grade 3 proteinuria, a grade 3-4 bleeding event, or bowel perforation * known history or clinical evidence of gilbert's syndrome, or is known to have any of the following genotypes: ugt1a1\*6/\*6, ugt1a1\*28/\*28, or ugt1a1\*6/\*28 * known allergy to any of the study treatment components, including any components used in the preparation of ramucirumab, or other contraindication to receive the study treatments * cirrhosis at a level of child-pugh b (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinical meaningful ascites resulting from cirrhosis; clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis

Keywords: second line metastatic colorectal cancer folfiri ramucirumab crc mcrc