Acetylsalicylic Acid and Eflornithine in Treating Patients at High Risk for Colorectal Cancer

NCT00983580 | Completed Phase 2 Results

• 5 other identifiers: NCI-2009-0119209-001758MC054AR01CA113681P30CA015083
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial is studying how well giving acetylsalicylic acid together with eflornithine works in treating patients at high risk for colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acetylsalicylic acid and eflornithine may prevent colorectal cancer.

Conditions

Adenomatous Polyp

Outcome Measures

Primary Outcomes (1)

• Adenoma Recurrence Rate for the Treatment Arm Relative to Placebo

  The primary endpoint is the proportion of participants with an adenoma recurrence at the 1-year follow-up colonoscopy exam. All eligible, randomized participants who have signed a consent form and received at least one follow-up endoscopy exam will be considered evaluable for the primary endpoint. This adenoma recurrence rate for DFMO + aspirin will be compared to double placebo to see if there is improvement in the adenoma recurrence rate in this patient population. A 1-sided Chi-square test was used to determine if there was a significant difference between treatment arms.

  At 1 year

Secondary Outcomes (4)

• ACF Characteristics vs Adenoma Recurrence Rate

  At baseline and 1 year

• Characterization of ACF

  Baseline

• Comparison of the Percent Change in ACF Number Across the 2 Treatment Arms

  At baseline and 12 months

• Safety, Tolerability, and Adverse Events of Study Treatment

  Up to 48 months from beginning treatment.

Other Outcomes (2)

• Effect of the Study Drugs and Placebo With Respect to Biomarkers

  Baseline and 12 months

• Gene Expression Analysis

  Baseline and 12 months

Study Arms (2)

Arm I (acetylsalicylic acid and eflornithine)

EXPERIMENTAL

Patients receive acetylsalicylic acid PO once daily and eflornithine PO twice daily on days 1-28.

Drug: Aspirin; Drug: Eflornithine; Other: Laboratory Biomarker Analysis; Other: Telephone-Based Intervention

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo PO three times daily on days 1-28.

Other: Laboratory Biomarker Analysis; Other: Placebo; Other: Telephone-Based Intervention

Interventions

Aspirin DRUG

Given PO

Also known as: Acetylsalicylic Acid, ASA, Aspergum, Ecotrin, Empirin, Entericin, Extren, Measurin

Arm I (acetylsalicylic acid and eflornithine)

Eflornithine DRUG

Given PO

Also known as: Alpha-Difluoromethylornithine, DFMO, difluoromethylornithine, Difluromethylornithine

Arm I (acetylsalicylic acid and eflornithine)

Laboratory Biomarker Analysis OTHER

Correlative study

Arm I (acetylsalicylic acid and eflornithine); Arm II (placebo)

Placebo OTHER

Given PO

Also known as: placebo therapy, PLCB, sham therapy

Arm II (placebo)

Telephone-Based Intervention OTHER

Ancillary studies

Arm I (acetylsalicylic acid and eflornithine); Arm II (placebo)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Current or prior advanced adenomas
• Advanced adenomas are defined as subject with polyps \>= 1 cm, tubulovillous adenomas (25-75 percent villous features), villous adenomas (\> 75 percent villous), or high-grade dysplasia
• Prior colon cancer (\>= 3 years out from invasive cancer)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Ability to under and the willingness to sign a written informed consent document
• Willingness to provide mandatory tissue for research purposes
• Negative pregnancy test =\< 7 days prior to randomization
• Hemoglobin (Hgb) within normal limits for institution/lab
• Platelet count \>= 100,000/ul
• White blood cell count (WBC) \>= 3,000/ul
• Alanine aminotransferase (ALT) =\< 2 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) =\< 2 x institutional ULN
• Total bilirubin =\< 1.5 x institutional ULN
• Serum calcium =\< institutional ULN
• Serum creatinine =\< 1.5 x institutional ULN

You may not qualify if:

• Any history of current or prior rectal cancer
• Known diagnosis of colon heritable cancer syndrome (familial adenomatous polyposis \[FAP\], hereditary nonpolyposis colorectal cancer \[HNPCC\]) or inflammatory bowel disease (Crohn's disease, ulcerative colitis)
• Inability to swallow pills
• Bleeding diathesis
• New diagnosis of carcinoma
• History of hypersensitivity to COX-2 inhibitors, sulfonamides, nonsteroidal antiinflammatory drugs (NSAIDs), salicylates, or ursodeoxycholic acid
• History of gastroduodenal ulcers documented =\< 1 year
• Known inability to participate in the scheduled follow-up tests
• Significant medical or psychiatric problems which would make the subject a poor protocol candidate, in the opinion of the treating physician
• Total colectomy
• Patients with a colostomy
• History of pelvic or rectal radiation therapy
• History of invasive carcinoma =\< 5 years (except subjects with Dukes A/B1 carcinoma =\< 5 years prior to pre-registration or any stage of colon cancer if \>= 3 years post surgical resection)
• Acute liver disease, unexplained transaminase elevations, or elevated serum calcium
• History of allergic reactions attributed to compounds of similar chemical composition to the study agents

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

University of Illinois College of Medicine - Chicago

Chicago, Illinois, 60612, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Adenomatous Polyps

Interventions

Aspirin; Eflornithine

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino

Results Point of Contact

• Title: Frank A. Sinicrope, M.D.
• Organization: Mayo Clinic

sinicrope.frank@mayo.edu

Study Officials

• Frank A Sinicrope

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2009
• First Posted: September 24, 2009
• Study Start: August 20, 2009
• Primary Completion: October 7, 2016
• Study Completion: August 13, 2019
• Last Updated: September 4, 2019
• Results First Posted: April 30, 2018

Record last verified: 2019-08

Locations

US (3)