S0820, Adenoma and Second Primary Prevention Trial - Full Text View

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.

Condition	Intervention	Phase
Colorectal Neoplasms	Drug: Eflornithine placebo & sulindac placebo Drug: eflornithine & sulindac placebo Drug: Eflornithine placebo & sulindac Drug: Eflornithine plus sulindac	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Prevention
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 Cancer, Phase III - Preventing Adenomas of the Colon With Eflornithine and Sulindac (PACES)

Resource links provided by NLM:

MedlinePlus related topics: Benign Tumors Cancer Colorectal Cancer

Drug Information available for: Sulindac Eflornithine hydrochloride

U.S. FDA Resources

Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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:

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 ] [ Designated as safety issue: No ]
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.
Toxicity by CTCAEv.4.0 at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Quantitative and qualitative toxicities at 3 years.
Examine interaction of treatment arm and genotype expression with respect to different outcomes. [ Time Frame: 3 years and 8 years ] [ Designated as safety issue: No ]
Interaction of intervention arm and baseline statin use with respect to 3-year event rate. [ Time Frame: 3 year ] [ Designated as safety issue: No ]
Interaction of intervention arm and baseline statin use with respect to 3-year event rate will be examined.
Evaluate SNPs associated with decreased adenoma/second primary CRC risk and AEs [ Time Frame: 3 years and 8 years ] [ Designated as safety issue: No ]
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.

Estimated Enrollment:	1340
Study Start Date:	March 2013
Estimated Study Completion Date:	July 2019
Estimated Primary Completion Date:	July 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 & 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 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 Eflornithine placebo 2 tablets PO daily for 3 years. Sulindac one 150 mg 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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

History of Stage 0-III colon cancer with primary resection 1 year previously
Patients with rectosigmoid cancers eligible if no RT administered
One-year post-operative colonoscopy and CT scans of chest, abdomen & pelvis showing no evidence of disease
Low risk or moderate risk of cardiovascular events
At least 30 days from completion of adjuvant chemo.
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
≥ 20 dB uncorrectable hearing loss for age of any two contiguous 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01349881

Contacts

Contact: Patricia N. O'Kane, B.S.	210-614-8808 ext 1011	pokane@swog.org
Contact: Kimberly J Farar, B.S.	210-614-8808 ext 1022	kfarar@swog.org

Show 271 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Cancer Prevention Pharmaceuticals, Inc.

Investigators

Principal Investigator:

Jason A. Zell, D.O., MPH

University of California, Irvine

More Information

No publications provided

Responsible Party:	Southwest Oncology Group
ClinicalTrials.gov Identifier:	NCT01349881 History of Changes
Other Study ID Numbers:	S0820, U10CA037429, NCI-2012-02067
Study First Received:	May 5, 2011
Last Updated:	May 17, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:

Eflornithine/sulindac prevention trial

Additional relevant MeSH terms:

Adenoma
Neoplasms
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Eflornithine

Sulindac
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Cyclooxygenase Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on May 21, 2013

S0820, Adenoma and Second Primary Prevention Trial (PACES)