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 or rectal cancer.

Category

IRB Number
20130412HU
NCT Number
NCT01349881
Open to Enrollment
Yes
Sponsor
Southwest Oncology Group -



Study Contact

Principal Investigator
Sukeshi Arora

Frances Crawford
(210) 450-5037
crawfordf1@uthscsa.edu

Sonia Creighton
(210) 450-1366
creighton@uthscsa.edu

Myrna Montenegro
(210) 450-5954
montenegro@uthscsa.edu

Courtney Nichols
(210) 450-1794
nicholsc2@uthscsa.edu

Mailbox Ctrc Regulatory Affairs
regaffapp@uthscsa.edu

Regulatory Staff
regaffstaff@uthscsa.edu

Kathleen Rodriguez
(210) 450-1365
rodriguezk3@uthscsa.edu

Benjamin Schleif
(210) 450-1366
schleifb@uthscsa.edu

Morgan Seekatz
(210) 450-1133
seekatz@uthscsa.edu



Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 intravenous corticosteroids on a regular basis,nonsteroidal anti-inflammatory drugs (NSAIDs), nor anticoagulants on a regular predictable intermittent basis. NSAID use must not exceed 10 days per month; Maximum aspirin dose

      • 100 mg per day or ≤ two 325 mg tablets per week. Inhaled steroids (i.e. for asthma or related conditions) are allowed.
    • Able to swallow oral medications
    • Laboratory: WBC ≥ 4.0 x 1000/mcL, platelets ≥ 100,000/mcL and hemoglobin > 11.0 g/dL. (A total WBC ≥ 3.1 x 1000/mcL is allowed for non-Hispanic black males and total WBC ≥ 3.4 x 1000/mcL for non-Hispanic black females. 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Factorial Assignment
Primary Purpose
Prevention
Masking
Triple (Participant, Care Provider, Investigator)
Condition
  • Colorectal Neoplasms
  • Arm Groups

    ArmDescriptionIntervention
    Experimental

    Eflornithine & sulindac placebo

    Eflornithine two 250 mg tablets PO daily for 3 years. Sulindac placebo one tablet PO daily for 3 years.
  • Drug: eflornithine & sulindac placebo

    Eflornithine two 250 mg tablets PO daily for 3 years. Sulindac placebo 1 tablet PO daily for 3 years.

  • Experimental

    Eflornithine plus sulindac

    Eflornithine two 250 mg tablets PO daily for 3 years. Sulindac one 150 mg tablet PO daily for 3 years.
  • Drug: Eflornithine plus sulindac

    Eflornithine two 250 mg tablets PO daily for 3 years. Sulindac one 150 mg tablet PO daily for 3 years.

  • Placebo Comparator

    eflornithine placebo & sulindac placebo

    Eflornithine placebo 2 tablets, PO, daily for 3 years. Sulindac placebo, 1 tablet, PO, daily for 3 years.
  • Drug: Eflornithine placebo & sulindac placebo

    Eflornithine placebo 2 tablets PO daily for 3 years. Sulindac placebo 1 tablet PO daily for 3 years

  • Experimental

    Eflornithine placebo & sulindac

    Eflornithine placebo 2 tablets PO daily for 3 years. Sulindac one 150 mg tablet PO daily for 3 years.
  • Drug: Eflornithine placebo & sulindac placebo

    Eflornithine placebo 2 tablets PO daily for 3 years. Sulindac placebo 1 tablet PO daily for 3 years

  • Drug: Eflornithine placebo & sulindac

    Eflornithine placebo 2 tablets PO daily for 3 years. Sulindac one 150 mg tablet PO daily for 3 years.