CALGB/SWOG 80405: Genome-Wide Association Study of Patients with Advanced or Metastatic Colorectal Cancer Treated with First-Line Chemotherapy Combined with Cetuximab and/or Bevacizumab

CALGB/SWOG 80405 (NCT00265850) was a randomized phase III study of bevacizumab, cetuximab, or the combination of these two monoclonal antibodies, in addition to systemic chemotherapy for patients with untreated metastatic adenocarcinoma of the colon or rectum. We prospectively collected germline DNA and conducted genome-wide association studies using clinical outcomes and molecular features.]]>
Inclusion Criteria Histologically or cytologically documented locally advanced or metastatic adenocarcinoma of the colon or rectum Only patients with a wildtype K-ras gene are eligible No prior systemic treatment for advanced or metastatic colorectal cancer No prior radiotherapy to > 25% of bone marrow ≥ 4 weeks since major surgery No previous or concurrent malignancy For FOLFIRI patients: No evidence of Gilbert's syndrome or of homozygosity for the UGT1A1*28 allele For FOLFOX patients: No ≥ grade 2 sensory peripheral neuropathy No known central nervous system metastases or carcinomatous meningitis No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung No pleural effusion or ascites that causes ≥ grade 2 dyspnea No predisposing colonic or small bowel disorders in which the symptoms are uncontrolled No uncontrolled seizure disorder or active neurological disease No current congestive heart failure; hypertension must be well controlled (< 160/90); and patients on full- dose anticoagulants must be on a stable dose of warfarin and have an in-range INR or be on a stable dose of LMW heparin No significant history of bleeding events or GI perforation; no recent (within 6 months) arterial thrombotic events; and no serious or non-healing wound, ulcer or bone fracture No known hypersensitivity to Chinese hamster ovary cell products or to recombinant human or murine antibodies Not pregnant and not nursing Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1 Age ≥ 18 Required Initial Laboratory Values: Granulocytes ≥ 1500/µL; Hemoglobin ≥ 9 g/dL; Platelet Count ≥ 100,000/µL; Creatinine ≤ 1.5 x ULN; Bilirubin ≤ 1.5 x mg/dL; Albumin ≥ 2.5 g/dL; Urinalysis ≤ 1+ protein ]]>
The clinical study began in September 2005 and ended in March 2012. Over the course of the clinical study, 3058 patients were preregistered or registered and 2334 patients were randomized to one of three treatment arms at 396 sites. In November 2008 patients with KRAS mutations in codons 12 and 13 were excluded from the study.In September 2009 the combination treatment arm of both cetuximab and bevacizumab with chemotherapy was dropped.]]>