Clinical Trial 19205

Cancer Type:
Interventions:Placebo; eflornithine; sulindac

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Mokenge Malafa

Overview

Study Title

Double Blind Placebo-Controlled Trial of Eflornithine and Sulindac to Prevent Recurrence of High Risk Adenomas and Second Primary Colorectal Cancers in Patients with Stage 0-III Colon or Rectal Cancer, Phase III-Preventing Adenomas of the Colon with Eflornithine and Sulindac (PACES)

Summary

The purpose of this study is to assess whether eflornithine 500 mg or sulindac 150 mg are effective in reducing the 3-year event rate of high risk adenoma or second primary colorectal cancer in Stage 0, I II and III colon cancer patients. The primary hypothesis will test the main effect of each agent, as well as the comparison of placebo alone to the combination of sulindac and eflornithine.

Objective

1.1 Primary Objective(s): a. 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. 1.2 Secondary Objective(s): a. To assess whether the combination of eflornithine and sulindac (compared to corresponding placebos) has efficacy against colorectal lesions with respect to high-grade dysplasia, adenomas with villous features, adenomas 1 cm or greater, multiple adenomas, any adenomas greater than or equal to 0.3cm, total advanced colorectal events, or total colorectal events. b. To assess quantitative and qualitative toxicities of patients when treated with the combination of eflornithine and sulindac compared to corresponding placebos. c. To evaluate a minimal set of tagging single nucleotide polymorphisms across multiple genes relevant to eflornithine and sulindac, in order to characterize associations with decreased adenoma/second primary colorectal (CRC) risk and adverse events. d. To evaluate biomarker responses of treatment effect using novel microfluidics-based digital droplet detection system. e. To explore the interaction of intervention arm and baseline statin use with respect to the 3-year event rate. f. To explore the interaction of the intervention arm and patient-reported meat consumption with respect to the 3-year event rate. g. To perform population pharmacokinetic (PK) analysis of eflornithine and sulindac in patients with previously treated Stage 0-III colon or rectal cancer. (Sites participating in PK sampling are listed on page 1a of the protocol).

Inclusion Criteria

  • History of Stage 0-III colon or rectal cancer with primary resection 1 year previously
  • Post-operative colonoscopy and CT scans of chest, abdomen and pelvis showing no evidence of disease
  • Must not have cardiovascular risk factors including unstable angina, history of myocardial infarction, or cerebrovascular accident, coronary artery bypass surgery, or NY Heart Assoc Class III or IV heart failure.
  • Participants must not have known uncontrolled hyperlipidemia (defined as LDL-C ≥ 190 mg/dL or triglycerides ≥ 500 mg/dL within the past 3 years or uncontrolled high blood pressure (systolic blood pressure > 150 mm Hg) within 28 days prior to registration
  • At least 30 days from completion of adjuvant chemo and radiation therapy (RT).
  • Presence of gastroesophageal reflux disease acceptable if controlled with medications
  • Not receiving or planning to receive concomitant corticosteroids,nonsteroidal anti-inflammatory drugs(NSAIDs), nor anticoagulants. Maximum aspirin dose 100 mg per day or ≤ two 325 mg tablets per week.
  • Able to swallow oral medications
  • Laboratory: WBC ≥ 4.0 x 10^3/mcL, platelets ≥ 100,000/mcL and hemoglobin > 11.0 g/dL. Serum bilirubin ≤ 2.0 mg/dL and AST (SGOT) or ALT(SGPT) ≤ 2 x IULN. Serum creatinine ≤ 1.5 x IULN
  • Zubrod Performance Status 0-1, 18 years of age or older
  • Will not participate in any other clinical trial for the treatment or prevention of cancer unless off protocol treatment, on follow-up phase only
  • Offered opportunity to participate in blood specimen banking

  • Exclusion Criteria

  • History of colon resection > 40 cm
  • Mid-low rectal cancer
  • Recurrent or metastatic disease
  • High cardiovascular risk; Uncontrolled hypertension
  • Planned radiation therapy or additional chemotherapy
  • Documented history of gastric/duodenal ulcer within last 12 months and/or current treatment or active symptoms of gastric/duodenal ulcer
  • Known history of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or inflammatory bowel disease
  • ≥ 30 dB uncorrectable hearing loss for age of any of the five tested frequencies on prestudy audiogram
  • Known hypersensitivity to sulindac or excipient byproducts. Previous asthma, urticaria, or allergic-type reaction to aspirin or other NSAIDs
  • Significant medical or psychiatric condition that would preclude study completion (8 years)
  • No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for > 5 years
  • Pregnant or nursing women. Women/men of reproductive potential must agree to use effective contraception