Eflornithine and/or Sulindac in Preventing Recurrence of High-Risk Adenomas and Second Primary Disease in Patients with Stage 0-III Colon or Rectal Cancer

Summary

Objectives

PRIMARY OBJECTIVE:
I. To assess whether the combination of eflornithine and sulindac is effective in reducing the three-year event rate (high-risk adenomas and second primary colorectal cancers) in patients with previously treated stage 0-III colon or rectal cancer.

SECONDARY OBJECTIVES:
I. To assess whether the combination of eflornithine and sulindac (compared to corresponding placebos) has efficacy against the total colorectal event rate as a single aggregate event, defined as including high-grade dysplasia, adenomas with villous features, adenomas 1 cm or greater, multiple adenomas, any adenomas >= 0.3 cm, and total advanced colorectal events (e.g., high risk adenoma, 2nd primary colorectal cancer, colorectal cancer recurrence, or metastasis).
II. To assess adverse events after combination of eflornithine and sulindac intervention compared to corresponding placebos.

EXPLORATORY OBJECTIVES:
I. To explore the effect of the intervention on each component of the total colorectal event rate.
II. To assess the total colorectal event rate at 8 years after follow-up.
III. To evaluate biomarker responses of treatment effect using blood-based circulating tumor deoxyribonucleic acid (ctDNA) testing for minimal residual disease.
IV. To perform population pharmacokinetic (PK) analysis of eflornithine and sulindac in patients with previously treated stage 0-III colon or rectal cancer.

OUTLINE: Patients are randomized to 1 of 4 arms.

ARM I: Patients receive eflornithine placebo orally (PO) once daily (QD) and sulindac placebo PO QD for 36 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive eflornithine PO QD and sulindac placebo PO QD for 36 months in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL PER PROTOCOL DATED 01/27/17)

ARM III: Patients receive eflornithine placebo PO QD and sulindac PO QD for 36 months in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL PER PROTOCOL DATED 01/27/17)

ARM IV: Patients receive eflornithine PO QD and sulindac PO QD for 36 months in the absence of disease progression or unacceptable toxicity.

Patients in all arms undergo colonoscopy and blood sample collection throughout the study.

After completion of study treatment, patients are followed up annually for 5 years.