SWOG S0820/PACES (preventing Adenomas of the Colon with Eflornithine and Sulindac): A Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial.

TPS3627 Background: After standard treatment for stage 0-III colorectal cancer (CRC), patients remain at increased risk for metachronous high-risk adenomas (HRAs) and 2ndprimary CRCs. Polyamines, in excess, are implicated in CRC carcinogenesis. In prior CRC chemoprevention clinical trials, low doses of polyamine-inhibitory agents eflornithine (E) and sulindac (S) demonstrated impressive efficacy. In the prior phase III clinical trial of colorectal adenoma (CRA) patients the combination E+S vs. placebo for 3-years resulted in > 92% reduction in risk of HRAs. Utility of these agents in colon cancer survivors, however, is unknown. Methods: Eligibility:Patients age > 18 with colon or rectosigmoid adenocarcinoma, stage 0, I, II, or III are eligible. Patients with major cardiovascular risk factors (MI, CVA) are excluded, as are patients with hearing loss > 30dB at 4K Hz and below. Daily low dose aspirin is allowed. Study Design: Patients are enrolled 9-15 months postoperatively for a 3-year duration in the randomized, double-blind, placebo-controlled Phase III trial. The intervention consists of eflornithine 250mg or matching placebo 2 tablets daily and sulindac 150mg or matching placebo one tablet daily. Baseline and end-of-study audiograms are required. Using a 2x2 factorial design, we will conduct 3 formal comparisons, each at the 2-sided, alpha = .0167 level with > 80% power. We tested the marginal effects of E &S, and the combined effect of E+S compared to placebo only. 1488 patients will be accrued over 5 years. Optional study components include pharmacogenetic, pharmacokinetic, & diet/lifestyle studies. The DSMC last met in October of 2014 and suggested that the trial continue as planned. Endpoints: The primary objective is to assess whether eflornithine 500 mg or sulindac 150mg are effective in reducing the 3-year event rate, defined as HRA or 2nd primary CRC, in Stage 0- III colon cancer patients. Hypothesis: In stage 0-III colon cancer patients during postoperative year 1-4, one or both of the single active agents will produce a 35% decrease in the rate of HRAs + 2nd primary CRCs; combination E+S will result in a 58% decrease compared to placebo alone. Clinical trial information: NCT01349881.