S0820, Adenoma and Second Primary Prevention Trial (PACES)

SWOG Cancer Research Network

Status and phase: Active, not recruiting; Phase 3

Conditions: Colorectal Neoplasms

Treatments: Drug: Eflornithine placebo & sulindac placebo; Drug: Eflornithine plus sulindac; Drug: eflornithine & sulindac placebo; Drug: Eflornithine placebo & sulindac

Study type: Interventional

Funder types: NETWORK; Industry; NIH

Identifiers

NCT01349881

NCI-2012-02067 (Other Identifier)

S0820

U10CA037429 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

The purpose of this study is to assess whether the combination of eflornithine 500 mg and sulindac 150 mg (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 >/= 0.3 cm, total advanced colorectal events, or total colorectal events.

Enrollment: 354 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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354 participants in 4 patient groups, including a placebo group

eflornithine placebo & sulindac placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Eflornithine placebo & sulindac placebo

Eflornithine & sulindac placebo

Experimental group

Description:

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

Treatment:

Drug: eflornithine & sulindac placebo

Eflornithine placebo & sulindac

Experimental group

Description:

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

Treatment:

Drug: Eflornithine placebo & sulindac

Eflornithine plus sulindac

Experimental group

Description:

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

Treatment:

Drug: Eflornithine plus sulindac