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Trial record 1 of 6 for:    "Colorectal Adenoma" | "Fibrinolytic Agents"
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Aspirin in Preventing Colorectal Cancer in Patients With Colorectal Adenoma

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ClinicalTrials.gov Identifier: NCT02965703
Recruitment Status : Recruiting
First Posted : November 17, 2016
Last Update Posted : October 15, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This randomized 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

Condition or disease Intervention/treatment Phase
Colorectal Adenoma Drug: Aspirin Other: Laboratory Biomarker Analysis Other: Placebo Other: Questionnaire Administration Phase 2

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Evaluating Intermittent Dosing of Aspirin for Colorectal Cancer Chemoprevention
Actual Study Start Date : January 16, 2018
Estimated Primary Completion Date : July 1, 2021
Estimated Study Completion Date : July 1, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

Arm Intervention/treatment
Experimental: Arm I (aspirin)
Patients receive aspirin PO daily for 12 weeks in the absence of unacceptable toxicity.
Drug: Aspirin
Given PO
Other Names:
  • Acetylsalicylic Acid
  • ASA
  • Aspergum
  • Ecotrin
  • Empirin
  • Entericin
  • Extren
  • Measurin

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Questionnaire Administration
Ancillary studies

Experimental: Arm II (aspirin, placebo)
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.
Drug: Aspirin
Given PO
Other Names:
  • Acetylsalicylic Acid
  • ASA
  • Aspergum
  • Ecotrin
  • Empirin
  • Entericin
  • Extren
  • Measurin

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Other: Questionnaire Administration
Ancillary studies

Placebo Comparator: Arm III (placebo)
Patients receive placebo PO daily for 12 weeks in the absence of unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies

Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Ratio of cell proliferation to apoptosis biomarkers (Ki67 index and BAX index) [ Time Frame: Up to 3 months ]

Secondary Outcome Measures :
  1. Ratio of cell proliferation (Ki-67)/apoptosis (TdT-mediated dUTP nick end labeling [TUNEL]) assessed in rectal biopsies [ Time Frame: Up to 12 weeks ]
    All of these variables will be described using appropriate statistics such as means (for continuous) and proportions (for discrete outcomes). Typically, basic scientists like to present the data to each other as bar graphs with standard deviation/standard error bars. Such and other, more appropriate graphic presentations, as confidence intervals for the true mean or true proportion will be provided, as well as scatter plots presenting two variables relationship in the Cartesian axes context. Tests of difference for continuous data (t-test, Wilcoxon test) and of association for discrete data (Chi-square, Fisher) will be provided.

  2. Ratio of cell proliferation (Ki-67)/necroptosis (MLKL) assessed in rectal biopsies [ Time Frame: Up to 12 weeks ]
    All of these variables will be described using appropriate statistics such as means (for continuous) and proportions (for discrete outcomes). Typically, basic scientists like to present the data to each other as bar graphs with standard deviation/standard error bars. Such and other, more appropriate graphic presentations, as confidence intervals for the true mean or true proportion will be provided, as well as scatter plots presenting two variables relationship in the Cartesian axes context. Tests of difference for continuous data (t-test, Wilcoxon test) and of association for discrete data (Chi-square, Fisher) will be provided.

  3. Fecal occult blood test assessed in stool samples [ Time Frame: Up to 12 weeks ]
    All of these variables will be described using appropriate statistics such as means (for continuous) and proportions (for discrete outcomes). Typically, basic scientists like to present the data to each other as bar graphs with standard deviation/standard error bars. Such and other, more appropriate graphic presentations, as confidence intervals for the true mean or true proportion will be provided, as well as scatter plots presenting two variables relationship in the Cartesian axes context. Tests of difference for continuous data (t-test, Wilcoxon test) and of association for discrete data (Chi-square, Fisher) will be provided.

  4. Methylation in CDKN2A (cell cycle regulation), MGMT (deoxyribonucleic acid [DNA] repair), DAPK1 (apoptosis), CDH1 (cell invasion), WNT16 (Wnt pathway), and RASSF1 (RAS signaling) assessed by pyrosequencing method [ Time Frame: Up to 12 weeks ]
    All of these variables will be described using appropriate statistics such as means (for continuous) and proportions (for discrete outcomes). Typically, basic scientists like to present the data to each other as bar graphs with standard deviation/standard error bars. Such and other, more appropriate graphic presentations, as confidence intervals for the true mean or true proportion will be provided, as well as scatter plots presenting two variables relationship in the Cartesian axes context. Tests of difference for continuous data (t-test, Wilcoxon test) and of association for discrete data (Chi-square, Fisher) will be provided.

  5. Change in colorectal mucosal nanoscale cellular structural assessed by rectal brushing by partial wave spectroscopy [ Time Frame: Baseline to 9 months ]
    All of these variables will be described using appropriate statistics such as means (for continuous) and proportions (for discrete outcomes). Typically, basic scientists like to present the data to each other as bar graphs with standard deviation/standard error bars. Such and other, more appropriate graphic presentations, as confidence intervals for the true mean or true proportion will be provided, as well as scatter plots presenting two variables relationship in the Cartesian axes context. Tests of difference for continuous data (t-test, Wilcoxon test) and of association for discrete data (Chi-square, Fisher) will be provided.

  6. Abundance of E. coli and fusobacterium assessed by rectal swabs [ Time Frame: Up to 9 months ]
    All of these variables will be described using appropriate statistics such as means (for continuous) and proportions (for discrete outcomes). Typically, basic scientists like to present the data to each other as bar graphs with standard deviation/standard error bars. Such and other, more appropriate graphic presentations, as confidence intervals for the true mean or true proportion will be provided, as well as scatter plots presenting two variables relationship in the Cartesian axes context. Tests of difference for continuous data (t-test, Wilcoxon test) and of association for discrete data (Chi-square, Fisher) will be provided.

  7. Dietary intake of calcium measured by the Food Frequency Questionnaire [ Time Frame: Up to 9 months ]
    All of these variables will be described using appropriate statistics such as means (for continuous) and proportions (for discrete outcomes). Typically, basic scientists like to present the data to each other as bar graphs with standard deviation/standard error bars. Such and other, more appropriate graphic presentations, as confidence intervals for the true mean or true proportion will be provided, as well as scatter plots presenting two variables relationship in the Cartesian axes context. Tests of difference for continuous data (t-test, Wilcoxon test) and of association for discrete data (Chi-square, Fisher) will be provided.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02965703


Locations
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United States, Tennessee
Vanderbilt University/Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Qi Dai    615-936-0707    Qi.dai@vanderbilt.edu   
Principal Investigator: Qi Dai         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Qi Dai Northwestern University

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02965703     History of Changes
Other Study ID Numbers: NCI-2016-01642
NCI-2016-01642 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
N01-CN-2012-00035
NCI2015-06-01 ( Other Identifier: Northwestern University )
NWU2015-06-01 ( Other Identifier: DCP )
N01CN00035 ( U.S. NIH Grant/Contract )
P30CA060553 ( U.S. NIH Grant/Contract )
First Posted: November 17, 2016    Key Record Dates
Last Update Posted: October 15, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Fibrinolytic Agents
Adenoma
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics