Aspirin in Preventing Colorectal Cancer in Patients with Colorectal Adenoma

Status: Active

Description

This phase IIa trial studies how well aspirin works in preventing colorectal cancer in patients with colorectal adenoma. Aspirin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria

Inclusion Criteria

  • Diagnosis of colorectal adenoma of any grade
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Leukocytes >= 3,000/microliter
  • Absolute neutrophil count >= 1,500/microliter
  • Platelets >= 150,000/microliter
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional ULN
  • Creatinine within normal institutional limits
  • Blood hemoglobin >= 12.0 g/dL
  • Alkaline phosphatase =< 1.5 x institutional ULN
  • Blood urea nitrogen (BUN) =< 40 mg/dL
  • Estimated glomerular filtration rate (eGFR) >= 45 mL/min
  • Negative fecal occult blood test
  • The effects of aspirin on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Current (within three weeks of randomization) or planned use during the study intervention of the following: * Aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), or COX-2 inhibitors * Anticoagulants, anti-platelet agents, or corticosteroids * Gingko * Ethanol consumption > 1 standard drinks/day for women, or > 2 standard drinks/day for men * Methotrexate (MTX) * Study participants will be instructed to use Tylenol or some other non-excluded agent to treat common ailments (i.e. headache/minor aches and pains)
  • History of * Any invasive malignancy within the past 2 years, with the exception of non-melanoma skin cancer * Chronic renal diseases or liver cirrhosis * Diseases such as anemia, peptic ulcer, gastrointestinal bleeding, active colitis and inflammatory bowel disease * Hemorrhagic stroke or uncontrolled hypertension
  • Participants may not be receiving any other investigational agents
  • History of allergic reactions or intolerance attributed to aspirin or compounds of similar chemical or biologic composition
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements
  • Women who are pregnant or breastfeeding; pregnant women are excluded from this study because aspirin has the potential for abortifacient effects; because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with aspirin, breastfeeding should be discontinued if the mother is treated with aspirin

Locations & Contacts

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: Active
Contact: Qi Dai
Phone: 615-936-0707
Email: Qi.dai@vumc.org

Trial Objectives and Outline

PRIMARY OBJECTIVE:

I. To test for the equivalency of the two aspirin schedules.

SECONDARY OBJECTIVES:

I. To evaluate the effects of aspirin treatments on the ratio of cell proliferation (Ki-67)/apoptosis (TUNEL) in rectal biopsies.

II. To evaluate the effects of aspirin treatments on the ratio of cell proliferation (Ki-67)/necroptosis (MLKL) in rectal biopsies.

III. To evaluate the effects of aspirin treatments on fecal occult blood test (measures of adverse events) as measured by stool samples.

IV. To evaluate the effects of aspirin treatments on methylation biomarkers in genes (i.e. CDKN2A [cell cycle regulation], MGMT [deoxyribonucleic acid (DNA) repair], DAPK1 [apoptosis], CDH1 [cell invasion], WNT16 [Wnt pathway] and RASSF1 [RAS signaling]) involved in colorectal carcinogenesis, as measured in rectal biopsies.

V. To evaluate the effects of aspirin treatments on colorectal mucosal nanoscale cellular structural changes measured by PWS (partial wave spectroscopy) obtained through rectal brushings.

VI. To evaluate the effects of aspirin treatments on abundance of E. coli and Fusobacterium in rectal swabs.

VII. To evaluate if the effects of aspirin arms may be modified by dietary intake of calcium as measured by the Food Frequency Questionnaire (FFQ).

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive aspirin orally (PO) daily for 12 weeks in the absence of unacceptable toxicity.

ARM II: Patients receive aspirin PO daily at weeks 1-3 and 7-9 and placebo PO daily at weeks 4-6 and 10-12 in the absence of unacceptable toxicity.

ARM III: Patients receive placebo PO daily for 12 weeks in the absence of unacceptable toxicity.

After completion of study, patients are followed up at 1 month.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Prevention

Lead Organization

Lead Organization
Northwestern University

Principal Investigator
Qi Dai

Trial IDs

Primary ID NCI2015-06-01
Secondary IDs NWU2015-06-01, NCI-2016-01642, N01-CN-2012-00035
Clinicaltrials.gov ID NCT02965703