BETHESDA, Md-Enrollment has begun in a randomized phase III trial to test two promising new drugs, irinotecan (Camptosar), also known as CPT-11, and oxaliplatin (an experimental platinum), as initial therapy for advanced colorectal cancer. The National Cancer Institute (NCI) expects that all of the more than 500 centers in the United States and Canada participating in the study will be enrolling patients by summer’s end.
BETHESDA, MdEnrollment has begun in a randomized phase III trial to test two promising new drugs, irinotecan (Camptosar), also known as CPT-11, and oxaliplatin (an experimental platinum), as initial therapy for advanced colorectal cancer. The National Cancer Institute (NCI) expects that all of the more than 500 centers in the United States and Canada participating in the study will be enrolling patients by summers end.
The Cooperative Colorectal Cancer Combination Chemotherapy Clinical Trial, informally known as 6C, will enroll about 1,700 patients with metastatic, locally advanced, or recurrent disease. Patients will be assigned to one of six arms with the aim of evaluating the two drugs against fluorouracil (5-FU) and leucovorin, the standard therapy for advanced colorectal cancer for more than 3 decades.
The standard therapy results in a response rate somewhere around 20% to 40%, the cancer takes about 5 months to progress, and generally survival is no longer than a year, said Barbara Conley, MD, a senior investigator in NCIs Cancer Therapy Evaluation Program. There are several studies, from the United States and Europe, that seem to suggest that the addition of either CPT-11 or oxaliplatin improves the response rate, compared to 5-FU and leucovorin. The evidence is not as great as to whether or not that translates into prolonged survival.
Some evidence suggests that irinotecan and oxaliplatin have a synergistic effect when combined with 5-FU and leucovorin. These are the first new drugs we have had to treat colorectal cancer in many years. The results may move the treatment of colorectal cancer a significant step forward, Dr. Conley said.
Irinotecan is approved in the United States for second-line therapy of metastatic colorectal cancer after first-line failure of 5-FU/leucovorin. Oxaliplatin is approved for the treatment of advanced colorectal cancer in France (where it is marketed as Eloxatine) and 14 other countries. It is being developed for the US market by Sanofi-Synthelabo (Paris) in a joint venture with Eli Lilly.
The primary endpoint is time to tumor progression; three secondary endpoints are increased survival, a comparison of side effects, and quality of life.
The North Central Cancer Treatment Group, chaired by Michael OConnell, MD, of the Mayo Clinic, will lead the study. Two other cooperative groups will participate in the trial, Cancer and Leukemia Group B and the National Cancer Institute of Canada Clinical Trials Group.
The participating centers are expected to complete 6C enrollment within 3 years. The 6C protocol calls for up to 12 months of follow-up, and NCI expects results will be available in 5 years or less.
The study design allows comparison of each of the two new drugs in combination with 5-FU/leucovorin, and of the two drugs in combination with each other, against the standard therapy. Two schedules of administration will be evaluated for each of the two test drugs. Patients will be randomized by computer to one of six groups and receive their drugs intravenously (see table). If needed, a second part of the trial will evaluate the more effective regimens against each other.
6C Trial Randomization Schema (All Drugs Are Given Intravenously)
Arm 1 (standard therapy)5-FU plus leucovorin on days 1 to 5 every 4 to 5 weeks
Arm 2Irinotecan and 5-FU plus leucovorin once a week for 4 weeks with 2 weeks rest
Arm 3Irinotecan on day 1 and 5-FU plus leucovorin on days 2 to 5, every 3 weeks
Arm 4Oxaliplatin on day 1 and 5-FU plus leucovorin on days 1 to 5, every 3 weeks
Arm 5Oxaliplatin on days 1 and 5-FU with leucovorin given for 48 hours, every 2 weeks
Arm 6Oxaliplatin and irinotecan on day 1, every 3 weeks
Any institution or physician belonging to an NCI-sponsored clinical trials cooperative group may enroll patients in the 6C trial. Other physicians can enroll patients by referring them to one of the three 6C participating cooperative groups.
A list of centers enrolling patients is available on the NCI website (http://cancertrials.nci.nih.gov) or by calling 1-800-4-CANCER.