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Celecoxib in Preventing Colorectal Cancer in Young Patients With a Genetic Predisposition for Familial Adenomatous Polyposis

Primary Purpose

Colorectal Cancer, Precancerous Condition

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
celecoxib
placebo
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Colorectal Cancer focused on measuring colon cancer, rectal cancer, familial adenomatous polyposis

Eligibility Criteria

10 Years - 14 Years (Child)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Diagnosis of familial adenomatous polyposis (FAP) based on genetic predisposition testing

  • Genotype-positive FAP (pathologic Adenomatous polyposis coli (APC) mutation)

    • No attenuated FAP genotype, defined by any of the following:

      • Mutation at the 5' end of APC and exon 4
      • Exon 9-associated phenotypes
      • 3' region mutations

  • Has an intact colon

    • No requirement for colectomy
    • Parent(s) do not desire colectomy (regardless of adenoma burden)

  • Colorectal adenoma burden as assessed by baseline colonoscopy

    • No diagnosis of severe dysplasia or greater
    • No more than 10 adenomas ≥ 1 cm
    • No more than 100 adenomas of any size
    • No evidence of anemia (hematocrit < 33%)
  • No new diagnosis of carcinoma

PATIENT CHARACTERISTICS:

  • White Blood Count (WBC) > 3,000/μL
  • Platelet count > 100,000/μL
  • Hemoglobin > 10.0 g/dL
  • Aspartate aminotransferase/alanine aminotransferase (AST/ALT) < 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase < 1.5 times ULN
  • Total bilirubin < 1.5 times ULN
  • Creatinine < 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of hypersensitivity to COX-2 inhibitors, sulfonamides, NSAIDs, or salicylates
  • No history of peptic ulcer disease
  • No significant medical or psychiatric problem that, in the opinion of the principal investigator, would make the patient a poor candidate for the study
  • No other unacceptable clinical risk (e.g., previously unknown bleeding diatheses)
  • No invasive carcinoma within the past 5 years

PRIOR CONCURRENT THERAPY:

  • More than 3 months since prior investigational agent
  • More than 6 months since prior chemotherapy
  • No prior radiotherapy to the pelvis
  • At least 3 months since prior NSAIDs (at any dose) at a frequency of ≥ 3 times/week
  • At least 1 month since prior NSAIDs (at any dose) at a frequency of < 3 times/week
  • At least 1 month since prior nasal steroids
  • Concurrent Nonsteroidal Antiinflammatory Drugs (NSAIDs) allowed provided they are administered ≤ 5 times per month
  • Concurrent orally inhaled steroids allowed provided they are administered for ≤ 4 weeks over a 6-month period
  • Concurrent oral or intravenous (IV) corticosteroids allowed provided they are administered for ≤ 2 consecutive weeks over a 6-month period
  • Concurrent proton pump inhibitors to treat gastric reflux allowed
  • No concurrent nasal steroids except mometasone (Nasonex)
  • No concurrent fluconazole, lithium, or adrenocorticosteroids

Sites / Locations

  • Cleveland Clinic Taussig Cancer Center
  • M. D. Anderson Cancer Center at University of Texas
  • Texas Children's Hospital
  • University of Texas Medical School at Houston

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I

Arm II

Arm Description

Patients receive oral celecoxib twice daily for 3 months in the absence of disease progression or unacceptable toxicity.

Patients receive oral placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Toxicity

Secondary Outcome Measures

Aberrant crypt foci (ACF) and adenoma burden in the entire colorectum
Elimination of the learning curve in a phase II/III trial
Comparison of sedation strategies based on local standards
Validation of technique for scoring ACFs
Short-term (3 month) impact of celecoxib on ACF count
Adherence
Influence of polymorphisms on age of onset of phenotype or on the number of colorectal polyps
Feasibility of psychosocial questionnaires
Pharmacokinetics (plasma drug trough concentrations)

Full Information

First Posted
May 23, 2008
Last Updated
November 5, 2018
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00685568
Brief Title
Celecoxib in Preventing Colorectal Cancer in Young Patients With a Genetic Predisposition for Familial Adenomatous Polyposis
Official Title
Phase I Pilot Toxicity/Methods Validation Study of Celecoxib in Genotype-Positive Children With Familial Adenomatous Polyposis
Study Type
Interventional

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
November 21, 2002 (Actual)
Primary Completion Date
April 21, 2006 (Actual)
Study Completion Date
April 21, 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of celecoxib may keep polyps and colorectal cancer from forming in patients with familial adenomatous polyposis. PURPOSE: This randomized phase I trial is studying the side effects and best dose of celecoxib in treating young patients with a genetic predisposition for familial adenomatous polyposis.
Detailed Description
OBJECTIVES: Primary Determine the safety and toxicity of celecoxib in pediatric patients with genotype-positive familial adenomatous polyposis. Secondary Determine the aberrant crypt foci (ACF) and adenoma burden in the entire colorectum of these patients. Eliminate the learning curve in a phase II/III trial (reproducibility of endoscopic techniques, tolerability of procedure). Compare sedation strategies based on local standards (monitored anesthesia care vs conscious sedation). Validate the ACF scoring technique. Establish the short-term (3 month) impact of celecoxib on ACF count in order to determine appropriateness of ACF as a pathologic endpoint in a phase II/III trial. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral celecoxib twice daily for 3 months in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive oral placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity. Patients undergo colonoscopy at baseline and at 3 months. Patients also complete psychosocial questionnaires at baseline. Blood samples are collected at baseline to assess the influence of polymorphisms (CYP2C9, uridine diphosphate (UDP)-glucuronosyl transferase, A6, glutathione S-transferase [GST] M1, and Glutathione S-transferase (GST) theta 1 (GSTT1)) on age of onset of phenotype or number of colorectal polyps. Plasma drug trough levels are assessed at baseline, 1 month, and 3 months. After completion of study treatment, patients are followed periodically for up to 2 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Precancerous Condition
Keywords
colon cancer, rectal cancer, familial adenomatous polyposis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients receive oral celecoxib twice daily for 3 months in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm II
Arm Type
Placebo Comparator
Arm Description
Patients receive oral placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
celecoxib
Intervention Description
Orally, twice daily for 3 months; 50 mg tablets. Celecoxib escalating doses starting at 4 mg/kg/day.
Intervention Type
Other
Intervention Name(s)
placebo
Intervention Description
Orally, twice daily for 3 months
Primary Outcome Measure Information:
Title
Toxicity
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Aberrant crypt foci (ACF) and adenoma burden in the entire colorectum
Time Frame
3 months
Title
Elimination of the learning curve in a phase II/III trial
Time Frame
3 months
Title
Comparison of sedation strategies based on local standards
Time Frame
3 months
Title
Validation of technique for scoring ACFs
Time Frame
3 months
Title
Short-term (3 month) impact of celecoxib on ACF count
Time Frame
3 months
Title
Adherence
Time Frame
3 months
Title
Influence of polymorphisms on age of onset of phenotype or on the number of colorectal polyps
Time Frame
3 months
Title
Feasibility of psychosocial questionnaires
Time Frame
3 months
Title
Pharmacokinetics (plasma drug trough concentrations)
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of familial adenomatous polyposis (FAP) based on genetic predisposition testing Genotype-positive FAP (pathologic Adenomatous polyposis coli (APC) mutation) No attenuated FAP genotype, defined by any of the following: Mutation at the 5' end of APC and exon 4 Exon 9-associated phenotypes 3' region mutations Has an intact colon No requirement for colectomy Parent(s) do not desire colectomy (regardless of adenoma burden) Colorectal adenoma burden as assessed by baseline colonoscopy No diagnosis of severe dysplasia or greater No more than 10 adenomas ≥ 1 cm No more than 100 adenomas of any size No evidence of anemia (hematocrit < 33%) No new diagnosis of carcinoma PATIENT CHARACTERISTICS: White Blood Count (WBC) > 3,000/μL Platelet count > 100,000/μL Hemoglobin > 10.0 g/dL Aspartate aminotransferase/alanine aminotransferase (AST/ALT) < 1.5 times upper limit of normal (ULN) Alkaline phosphatase < 1.5 times ULN Total bilirubin < 1.5 times ULN Creatinine < 1.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of hypersensitivity to COX-2 inhibitors, sulfonamides, NSAIDs, or salicylates No history of peptic ulcer disease No significant medical or psychiatric problem that, in the opinion of the principal investigator, would make the patient a poor candidate for the study No other unacceptable clinical risk (e.g., previously unknown bleeding diatheses) No invasive carcinoma within the past 5 years PRIOR CONCURRENT THERAPY: More than 3 months since prior investigational agent More than 6 months since prior chemotherapy No prior radiotherapy to the pelvis At least 3 months since prior NSAIDs (at any dose) at a frequency of ≥ 3 times/week At least 1 month since prior NSAIDs (at any dose) at a frequency of < 3 times/week At least 1 month since prior nasal steroids Concurrent Nonsteroidal Antiinflammatory Drugs (NSAIDs) allowed provided they are administered ≤ 5 times per month Concurrent orally inhaled steroids allowed provided they are administered for ≤ 4 weeks over a 6-month period Concurrent oral or intravenous (IV) corticosteroids allowed provided they are administered for ≤ 2 consecutive weeks over a 6-month period Concurrent proton pump inhibitors to treat gastric reflux allowed No concurrent nasal steroids except mometasone (Nasonex) No concurrent fluconazole, lithium, or adrenocorticosteroids
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick M. Lynch, MD, JD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Cleveland Clinic Taussig Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
M. D. Anderson Cancer Center at University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Texas Medical School at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20234350
Citation
Lynch PM, Ayers GD, Hawk E, Richmond E, Eagle C, Woloj M, Church J, Hasson H, Patterson S, Half E, Burke CA. The safety and efficacy of celecoxib in children with familial adenomatous polyposis. Am J Gastroenterol. 2010 Jun;105(6):1437-43. doi: 10.1038/ajg.2009.758. Epub 2010 Mar 16.
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Celecoxib in Preventing Colorectal Cancer in Young Patients With a Genetic Predisposition for Familial Adenomatous Polyposis

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