Clinical Trials /

S0820, Adenoma and Second Primary Prevention Trial

NCT01349881

Description:

The investigators hypothesize that the combination of eflornithine and sulindac will be effective in reducing a three-year event rate of adenomas and second primary colorectal cancers in patients previously treated for Stages 0 through III colon or rectal cancer.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: S0820, Adenoma and Second Primary Prevention Trial
  • Official Title: A 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)

Clinical Trial IDs

  • ORG STUDY ID: S0820
  • SECONDARY ID: U10CA037429
  • SECONDARY ID: NCI-2012-02067
  • NCT ID: NCT01349881

Conditions

  • Colorectal Neoplasms

Interventions

DrugSynonymsArms
Eflornithine placebo & sulindac placeboeflornithine placebo & sulindac placebo
eflornithine & sulindac placeboEflornithine & sulindac placebo
Eflornithine placebo & sulindacEflornithine placebo & sulindac
Eflornithine plus sulindacEflornithine plus sulindac

Purpose

The investigators hypothesize that the combination of eflornithine and sulindac will be effective in reducing a three-year event rate of adenomas and second primary colorectal cancers in patients previously treated for Stages 0 through III colon cancer.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
eflornithine placebo & sulindac placeboPlacebo ComparatorEflornithine placebo 2 tablets, PO, daily for 3 years. Sulindac placebo, 1 tablet, PO, daily for 3 years.
  • Eflornithine placebo & sulindac placebo
Eflornithine & sulindac placeboExperimentalEflornithine two 250 mg tablets PO daily for 3 years. Sulindac placebo one tablet PO daily for 3 years.
  • eflornithine & sulindac placebo
Eflornithine placebo & sulindacExperimentalEflornithine placebo 2 tablets PO daily for 3 years. Sulindac one 150 mg tablet PO daily for 3 years.
  • Eflornithine placebo & sulindac
Eflornithine plus sulindacExperimentalEflornithine two 250 mg tablets PO daily for 3 years. Sulindac one 150 mg tablet PO daily for 3 years.
  • Eflornithine plus sulindac

Eligibility Criteria

        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 & 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.

          -  Patients 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 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 103/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 PS 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:3-year event rate after registration among Stage 0-III colon cancer patients. (An event is defined as high-risk adenoma or second primary colorectal cancer.)
Time Frame:3 years
Safety Issue:
Description:The primary objective is to assess whether eflornithine 500 mg or sulindac 150 mg are effective in reducing the 3-year event rate, defined as high risk adenoma or 2nd primary colorectal cancer, in Stage 0, I, II, and III colon cancer patients.

Secondary Outcome Measures

Measure:Incidence of colorectal lesions with respect to high-grade dysplasia, adenomas with villous features, adenomas 1 cm or greater, multiple adenomas, polyps >/= 0.3 cm, total advanced colorectal events or total colorectal events at 3 years.
Time Frame:3 years and 8 years
Safety Issue:
Description:Incidence of colorectal lesions with respect to high grade dysplasia, adenomas with villous features, adenomas 1 cm or greater, multiple adenomas, polyps >/= 0.3 cm, total advanced colorectal events (defined as the number of patients with at least one high risk adenoma, 2nd primary colorectal cancer, colorectal cancer recurrence, or metastasis) or total colorectal cancer events (defined as the number of patients with at least one advanced colorectal event or polyp)at 3 years and 8 years.
Measure:Toxicity by CTCAEv.4.0 at 3 years
Time Frame:3 years
Safety Issue:
Description:Quantitative and qualitative toxicities at 3 years.
Measure:Examine interaction of treatment arm and genotype expression with respect to different outcomes.
Time Frame:3 years and 8 years
Safety Issue:
Description:
Measure:Interaction of intervention arm and baseline statin use with respect to 3-year event rate.
Time Frame:3 year
Safety Issue:
Description:Interaction of intervention arm and baseline statin use with respect to 3-year event rate will be examined.
Measure:Evaluate SNPs associated with decreased adenoma/second primary CRC risk and AEs
Time Frame:3 years and 8 years
Safety Issue:
Description: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 CRC risk and adverse events.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Southwest Oncology Group

Trial Keywords

  • Eflornithine/sulindac prevention trial

Last Updated

July 13, 2017