This phase III trial aims to determine the benefits of using the drugs eflornithine and sulindac (Clinoril) in the prevention of high risk adenomas and secondary colorectal cancers. Researchers will look at the number of recurrences over a 3 year period while administering the drugs.
The details
Patients previously treated for colorectal cancer (stages 0 to III) are at a higher risk of cancer recurrence. Usually, the second cancer develops from abnormal structures on the lining of the colon called adenomas. Once these develop, they can grow into high-risk adenomas which represent pre-cancerous lesions.
Preventing adenoma formation is useful in lowering the risk of cancer recurrences after curative treatment.
Eflornithine is a drug used in creams that stop the abnormal growth of facial hair. However, it is hypothesized that it is also effective in preventing adenoma formation - it blocks an enzyme responsible for cell growth. Sulindac is an anti-inflammatory drug that has also been found to be effective in slowing down adenoma development. It is expected that giving the two drugs together will achieve the best response.
Who are they looking for?
Researchers will recruit about 1340 patients previously treated for stage 0 to III colon cancer with no evidence of residual disease. Participants should be in good general health, with normal or near-normal results of routine blood tests and a low to moderate risk of cardiac events. Patients should not be taking anti-inflammatory drugs and long-term aspirin use should not exceed 100 mg daily. Chemotherapy should be completed at least 30 days before the start of the trial.
Patients cannot be included in this trial if they had more than 40 cm of their colon removed, if treated for mid-low rectal cancer or if there is evidence of recurrent or metastatic disease. Other exclusion criteria: pregnancy, high cardiovascular risk, history of gastric/duodenal ulcer within the past 12 months, inflammatory bowel disease, family history of polyposis and known allergies to sulindac or other anti-inflammatory agents.
How will it work
In order to assess the efficacy of the two drugs, patients will be divided into 4 groups. One group will receive placebo only (an inactive drug) as Eflornithine placebo plus Sulindac placebo.A second group will receive Eflornithine as two 250 mg tablets daily for 3 years and Sulindac placebo one tablet daily for 3 years. A third group will receive Eflornithine placebo as 2 tablets daily for 3 years and Sulindac one 150 mg tablet daily for 3 years. The fourth group will receive Eflornithine as two 250 mg tablets daily for 3 years and Sulindac one 150 mg tablet daily for 3 years.
The primary objective is to evaluate whether eflornithine 500 mg (two tablets) or sulindac 150 mg are effective in reducing the 3-year event rate, defined as high risk adenoma or second primary colorectal cancer, in Stage 0, I, II, and III colon cancer patients.
Other outcomes to be investigated include: the number of new colorectal lesions that are not defined as high-risk, treatment-related side effects, drug interactions, genetic mutations associated with an increased risk of developing adenomas.
