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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2009-00841 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| CDR0000652929 | |||
| NCI 04-2-03 | Other Identifier | Northwestern University | |
| NWU04-2-03 | Other Identifier | DCP | |
| N01CN35157 | U.S. NIH Grant/Contract | View source |
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This randomized phase II trial is studying how well aspirin works in preventing colorectal cancer in patients at increased risk of colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of aspirin may prevent colorectal cancer.
PRIMARY OBJECTIVE:
I. Determine whether acetylsalicylic acid (aspirin) will alter spectral markers (i.e., spectral slope and fractal dimension) in distal colonic mucosa of patients who are at increased risk for the development or recurrence of colorectal cancer.
SECONDARY OBJECTIVES:
I. Assess the effect of this drug on colonic epithelial apoptosis and cell proliferation in these patients.
II. Assess the effect of this drug on rectal prostaglandin levels in these patients.
III. Assess the effect of this drug on platelet cyclooxygenase activity in these patients.
IV. Correlate changes in spectral markers with UGT1A6 genotype in patients treated with this drug.
OUTLINE: This is a multicenter, randomized, double-blind, placebo-controlled study. Patients are stratified by clinical site and adenoma/carcinoma maximal size. Patients with abnormal spectral biomarkers are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oral acetylsalicylic acid (aspirin) once daily.
ARM II: Patients receive oral placebo once daily.
In both arms, treatment continues for 3 months in the absence of unacceptable toxicity.
Patients undergo flexible sigmoidoscopy and biopsies as well as blood collection at baseline (during prestudy colonoscopy) and at completion of study treatment for comparison of spectral signatures with biomarkers of both aspirin activity (including plasma cyclooxygenase activity and rectal prostaglandin levels) as well as with biomarkers associated with antineoplastic alteration (including apoptosis and cell proliferation). UGT1A6 genotyping analysis is also performed.
After completion of study treatment, patients are followed at 3 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I | Experimental | Patients receive oral acetylsalicylic acid (aspirin) once daily. |
|
| Arm II | Placebo Comparator | Patients receive oral placebo once daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| acetylsalicylic acid | Drug | Given orally |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Spectral Slope or SPEC) From Baseline to 3 Months. | Spectral marker assessment was performed via LEBS analysis (low-coherence enhanced backscattering spectroscopy) on the uninvolved mucosal biopsies of subjects taken at baseline and after 3 months of treatment with either aspirin or placebo. SPEC characterizes the size distribution of macromolecular complexes and other intracellular structures, with a decrease of the spectral slope implying a shift of the size distribution of intracellular structures toward smaller sizes. Spectral markers SPEC and FRAC provide a measure of the fundamental characteristics of the tissue nanoscale architecture. | 3 months from baseline colonoscopy to end of intervention. |
| Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Fractal Dimension or FRAC) From Baseline to 3 Months. | Spectral marker assessment was performed via LEBS analysis (low-coherence enhanced backscattering spectroscopy) on the uninvolved mucosal biopsies of subjects taken at baseline and after 3 months of treatment with either aspirin or placebo. FRAC characterizes the spatial autocorrelation function of mass density distribution in tissue. SPEC and FRAC provide a measure of the fundamental characteristics of the tissue nanoscale architecture | 3 months from baseline colonoscopy to end of intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| Colonic Epithelial Apoptosis as Measured by Immunohistochemical Detection of Cleaved Caspase 3 | Evaluate the effect of aspirin on colonic epithelial apoptosis and cell proliferation as assessed by immunohistochemical detection of cleaved caspase 3 .These were performed on samples that had been previously analyzed for 4D-ELF. | 3 months from baseline colonoscopy to end of intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| Platelet Cyclooxygenase (COX) Activity as Measured by a Peroxidase-based COX Enzyme Activity Assay | Evaluate the effect of aspirin on platelet COX activity as measured by a peroxidase-based Cox enzyme activity assay. | 3 months from baseline colonoscopy to end of intervention. |
Criteria:
No active or metastatic cancer within the past 6 months
Scheduled to undergo colonoscopy for colonic neoplasia surveillance
Hemoglobin >= 12.0 g/dL
Platelet count >= 120,000/mm^3
AST or ALT =< 1.5 times upper limit of normal (ULN)
Alkaline phosphatase =< 1.5 times ULN
Bilirubin =< 1.5 times ULN
BUN =< 40 mg/dL
Glomerular filtration rate >= 45 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No coagulopathy
No anemia
No history of peptic ulcer disease or gastrointestinal hemorrhage
No history of cerebrovascular accident
No uncontrolled hypertension
No history of intolerance or allergy to aspirin or to NSAIDs
No liver disease as manifested by signs or symptoms of cirrhosis
No endoscopic or radiographic evidence of portal hypertension
No active colitis by endoscopy
No history of inflammatory bowel disease
No requirement for aspirin as medical therapy (i.e., post-myocardial infarction or transient ischemic attack)
No untreated helicobacter pylori infection
History of significant colonic neoplasia, defined as 1 of the following:
INR =< 1.5
At least 6 months since prior cancer treatment
No other concurrent acetylsalicylic acid (aspirin)-containing products or non-steroidal anti-inflammatory drugs (NSAIDs)
No concurrent systemic corticosteroids
No other concurrent anticoagulants or antiplatelet agents
No concurrent investigational drugs
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| Name | Affiliation | Role |
|---|---|---|
| Hemant Roy | Northwestern University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University | Chicago | Illinois | 60611 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26503631 | Derived | Roy HK, Turzhitsky V, Wali R, Radosevich AJ, Jovanovic B, Della'Zanna G, Umar A, Rubin DT, Goldberg MJ, Bianchi L, De La Cruz M, Bogojevic A, Helenowski IB, Rodriguez L, Chatterton R, Skripkauskas S, Page K, Weber CR, Huang X, Richmond E, Bergan RC, Backman V. Spectral biomarkers for chemoprevention of colonic neoplasia: a placebo-controlled double-blinded trial with aspirin. Gut. 2017 Feb;66(2):285-292. doi: 10.1136/gutjnl-2015-309996. Epub 2015 Oct 26. |
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A total of 110 subjects met the clinical definition of high risk for colorectal cancer, were entered onto the trial, and underwent initial spectral analysis. Of these, 81 had a cancer-associated spectral signature in histologically normal colonic mucosa.79 of these 81 subjects were randomized and began the study intervention
The study opened to accrual 02/22/2007 and closed to accrual 08/10/2009. Subjects were recruited at Northwestern University and University of Chicago.
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| ID | Title | Description |
|---|---|---|
| FG000 | Acetylsalicylic Acid | Patients receive oral acetylsalicylic acid (aspirin) once daily. |
| FG001 | Placebo | Patients receive oral placebo once daily. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
72 of the 79 subjects who were randomized completed the primary endpoint (3-month tissue biopsy); 36 from each arm.
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| ID | Title | Description |
|---|---|---|
| BG000 | Acetylsalicylic Acid | Patients receive oral acetylsalicylic acid (aspirin) once daily. |
| BG001 | Placebo | Patients receive oral placebo once daily. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Spectral Slope or SPEC) From Baseline to 3 Months. | Spectral marker assessment was performed via LEBS analysis (low-coherence enhanced backscattering spectroscopy) on the uninvolved mucosal biopsies of subjects taken at baseline and after 3 months of treatment with either aspirin or placebo. SPEC characterizes the size distribution of macromolecular complexes and other intracellular structures, with a decrease of the spectral slope implying a shift of the size distribution of intracellular structures toward smaller sizes. Spectral markers SPEC and FRAC provide a measure of the fundamental characteristics of the tissue nanoscale architecture. | Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa. | Posted | Mean | Standard Deviation | micron^-1 | 3 months from baseline colonoscopy to end of intervention. |
|
3 months from baseline colonoscopy to end of intervention and repeat colonoscopy.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Acetylsalicylic Acid | Patients receive oral acetylsalicylic acid (aspirin) once daily. acetylsalicylic acid: Given orally laboratory biomarker analysis: Correlative study |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood/Bone Marrow: Hemoglobin | Blood and lymphatic system disorders | CTCAE v. 3.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Seema Khan | Northwestern University | 312-503- 4236 | skhan@nm.org |
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| ID | Term |
|---|---|
| D003110 | Colonic Neoplasms |
| D011230 | Precancerous Conditions |
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
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| ID | Term |
|---|---|
| D001241 | Aspirin |
| ID | Term |
|---|---|
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
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| placebo | Drug | Given orally |
|
|
| laboratory biomarker analysis | Other | Correlative study |
|
| Changes in Colonic Cell Proliferation as Measured by Immunohistochemical Detection of Ki67 | Evaluate the effect of aspirin on colonic epithelial apoptosis and cell proliferation as assessed by immunohistochemical detection of Ki-67. These were performed on samples that had been previously analyzed for 4D-ELF. | 3 months from baseline colonoscopy to end of intervention. |
| Rectal Prostaglandin Levels as Measured by ELISA | Evaluate the effect of aspirin on rectal prostaglandin levels. | 3 months from baseline colonoscopy to end of intervention. |
| Medical Contraindication |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Patients receive oral acetylsalicylic acid (aspirin) 325 mg once daily. |
| OG001 | Placebo | Patients receive oral placebo once daily. |
|
|
|
| Primary | Change of a Spectral Biomarker for Colonic Carcinogenesis (Called Fractal Dimension or FRAC) From Baseline to 3 Months. | Spectral marker assessment was performed via LEBS analysis (low-coherence enhanced backscattering spectroscopy) on the uninvolved mucosal biopsies of subjects taken at baseline and after 3 months of treatment with either aspirin or placebo. FRAC characterizes the spatial autocorrelation function of mass density distribution in tissue. SPEC and FRAC provide a measure of the fundamental characteristics of the tissue nanoscale architecture | Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa | Posted | Mean | Standard Deviation | unitless | 3 months from baseline colonoscopy to end of intervention. |
|
|
|
|
| Secondary | Colonic Epithelial Apoptosis as Measured by Immunohistochemical Detection of Cleaved Caspase 3 | Evaluate the effect of aspirin on colonic epithelial apoptosis and cell proliferation as assessed by immunohistochemical detection of cleaved caspase 3 .These were performed on samples that had been previously analyzed for 4D-ELF. | Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa. | Posted | Mean | Standard Deviation | Percentage of Total Cells | 3 months from baseline colonoscopy to end of intervention. |
|
|
|
| Secondary | Changes in Colonic Cell Proliferation as Measured by Immunohistochemical Detection of Ki67 | Evaluate the effect of aspirin on colonic epithelial apoptosis and cell proliferation as assessed by immunohistochemical detection of Ki-67. These were performed on samples that had been previously analyzed for 4D-ELF. | Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa. | Posted | Mean | Standard Deviation | Percentage of Total Cells | 3 months from baseline colonoscopy to end of intervention. |
|
|
|
| Secondary | Rectal Prostaglandin Levels as Measured by ELISA | Evaluate the effect of aspirin on rectal prostaglandin levels. | Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa. | Posted | Mean | Standard Deviation | pg/ml | 3 months from baseline colonoscopy to end of intervention. |
|
|
|
| Other Pre-specified | Platelet Cyclooxygenase (COX) Activity as Measured by a Peroxidase-based COX Enzyme Activity Assay | Evaluate the effect of aspirin on platelet COX activity as measured by a peroxidase-based Cox enzyme activity assay. | Subjects at high risk for colorectal cancer (CRC) with a cancer-associated spectral marker signature in histologically normal colonic mucosa. | Posted | Mean | Standard Deviation | pg/ml | 3 months from baseline colonoscopy to end of intervention. |
|
|
|
| 0 |
| 40 |
| 17 |
| 40 |
| EG001 | Placebo | Patients receive oral placebo once daily. placebo: Given orally laboratory biomarker analysis: Correlative study | 0 | 39 | 21 | 39 |
| Blood/Bone Marrow: Other | Blood and lymphatic system disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Hemorrhage with Surgery | Blood and lymphatic system disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Hypertension | Cardiac disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Heartburn | Gastrointestinal disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Pain: Stomach | General disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Pain: Abdomen Nos | General disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Pain: Head/Headache | General disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Pain: Other | General disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Pain: Joint | General disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Pain: Extremity - Limb | General disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Pain: Uterus | General disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Constitutional Symptoms: Fever | General disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Constitutional Symptoms: Insomnia | General disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Constitutional Symptoms: Weight Gain | Gastrointestinal disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Constitutional Symptoms: Other | General disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Rhinitis | Immune system disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Upper Airway Nos | Infections and infestations | CTCAE v. 3.0 | Systematic Assessment |
|
| Infection - Other | Infections and infestations | CTCAE v. 3.0 | Systematic Assessment |
|
| Metabolic/Lab - Other | Metabolism and nutrition disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| AST | Metabolism and nutrition disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| ALT | Metabolism and nutrition disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Cystitis | Renal and urinary disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Sexual - Other | Reproductive system and breast disorders | CTCAE v. 3.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE v. 3.0 | Systematic Assessment |
|
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| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |