Stage III (IIIB or IIIC) Colon Cancer Clinical Trial
Official title:
A Phase III Randomized Placebo-Controlled Study Evaluating Regorafenib Following Completion of Standard Chemotherapy for Patients With Stage III Colon Cancer
This study is a randomized, double-blind, post-chemotherapy, adjuvant phase III clinical trial. The primary aim of this study is to determine the value of regorafenib in improving disease-free survival (DFS). Patients with Stage III (IIIB or IIIC) colon cancer as defined by the 7th Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual are randomized 1:1 to placebo or the experimental agent regorafenib following completion of at least four months of standard adjuvant therapy (e.g., 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX) , capecitabine, oxaliplatin (CapeOx), and other).
The primary aim of this study is to determine the value of regorafenib in improving DFS. The secondary aims are to evaluate the dose tolerance and long term toxicity of two years of regorafenib following standard adjuvant therapy, and to evaluate the effect of the use of regorafenib in overall survival (OS). Eligible patients in this double-blind study will be randomized to take either regorafenib 120 mg or placebo orally, once daily for 21 consecutive days of a 28 day cycle for 26 cycles (2 years). Accrual for this study will be approximately 1118 randomized patients. These 1118 patients will provide approximately 313 DFS events at the time of primary analysis. An initial futility analysis will be performed when 312 patients have been on study at least 3 months. The decision to continue the trial will be determined by success of both early stopping endpoints defined as follows: - The toxicity profile of regorafenib compared to placebo is acceptable. - The regorafenib regimen is tolerable for prolonged administration. An estimated compliance rate of 60% at 6 months for regorafenib will be required for continuation of the study. If toxicity is acceptable and compliance with regorafenib is at least 60% nominally, then accrual will continue. The second futility analysis will be conducted when approximately 67 DFS events are observed. Trial conduct and accrual will continue unless the primary endpoint (DFS) trends too far in the opposite direction (hazard ratio greater than or equal to 1.1). Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. NSABP C-13 will include a Behavioral and Health Outcomes correlative science component. A C-13 Quality of Life (QOL) questionnaire will be administered at baseline (after consent and prior to randomization) and at 3 months, 6 months, 12 months, 18 months, 24 months, and 30 months. Submission of blood samples for C-13 correlative science studies will be a study requirement for all patients. Submissions will also include archived primary tumor tissue from the resected colon primary. Blood samples for pharmacokinetics (PK) will be collected on Day 15 of Cycle 1 and Day 15 of Cycle 2, with additional blood samples for biomarkers collected at various time points for future analysis. ;