SIGNIFICANT ONGOING CLINICAL TRIALS

Definitive, Late Phase Trials

Randomized Trials Evaluate the Addition of Bevacizumab or Cetuximab in Combination with Chemotherapy in Patients with Resected Colon Cancer

Multiple randomized trials over the last three decades have validated the use of systemic therapy to prolong survival for patients with stage III colon cancer. The current standard for adjuvant therapy in patients with stage III colon cancer that has been surgically resected is FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin).

Recent phase III trials that evaluated newer, targeted agents in patients with metastatic colorectal cancer demonstrated the clinical benefit of two combinations: bevacizumab, a recombinant humanized monoclonal antibody directed against the vascular endothelial growth factor (VEGF) preventing the growth and maintenance of tumor blood vessels, with chemotherapy; and cetuximab, a recombinant, chimeric monoclonal antibody directed against the epidermal growth factor receptor (EGFR) with antineoplastic activity, with chemotherapy. These combinations are now being evaluated in three large, phase III randomized trials in patients who have undergone complete surgical resection of their colon cancer.

• National Surgical Adjuvant Breast and Bowel Project Study
  http://clinicaltrials.gov/ct2/show/NCT00096278

  The National Surgical Adjuvant Breast and Bowel Project conducted a large, randomized phase III trial, NSABP C-08, in patients with stage II or III colon cancer to evaluate the clinical benefit of adding bevacizumab to FOLFOX adjuvant chemotherapy along with an additional 6 months of bevacizumab alone. This study opened approximately 6 months after FDA approval of bevacizumab in combination with 5-fluorouracil-based chemotherapy for the treatment of metastatic colorectal cancer. The study enrolled over 2,700 patients between September 2004 and October 2006 and results are pending.

• North Central Cancer Treatment Group Study
  http://clinicaltrials.gov/ct2/show/NCT00079274

  The North Central Cancer Treatment Group is leading a large, randomized, intergroup phase III trial, N0147, in patients with stage III colon cancer to evaluate the clinical benefit of adding cetuximab to FOLFOX adjuvant chemotherapy. This study on the clinical benefit of cetuximab was also activated within approximately 6 months of the FDA approval of cetuximab as single-agent therapy to treat patients with advanced colorectal cancer that has spread to other parts of the body. Since September 2004, the N0147 study has enrolled 1,819 patients out of a total accrual target of approximately 2,300 patients. The study is projected to close to accrual in the first half of 2008.

• Eastern Cooperative Oncology Group
  http://clinicaltrials.gov/ct2/show/NCT00217737

  The role of adjuvant therapy in patients with stage II colon cancer (cancer that extends through the wall of the colon but not to the lymph nodes or other organs) is controversial. ECOG is leading a large, intergroup phase III trial, E5202, for patients with stage II colon cancer in which specific biological features (tumor markers) believed to predict tumor recurrence will be used to define a “high-risk” group of patients with stage II colon cancer. Tumors from patients will be assessed for microsatellite stability (MSS) and loss of heterozygosity (LOH) at chromosome 18q. Patients with disease that is at “high-risk” for recurrence based on MSS status and LOH at chromosome 18q are randomized to standard chemotherapy (FOLFOX) or to standard chemotherapy in combination with bevacizumab. Patients with disease that is considered at “low-risk” of recurrence are assigned to observation only.