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Study Summary
No. 2006-0040:.......Colorectal......Patrick Lynch......Gastroenterology/Hepatology and Nutrition
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Study Summary Title
Study Summary
Number:
2006-0040
Study Title:A Phase III Placebo-Controlled Trial of Celecoxib in Genotype Positive Subjects with Familial Adenomatous Polyposis
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Physician New Patient Referral
Name:Patrick LynchPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Gastroenterology/Hepatology and NutritionReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-794-5073
Contact us about clinical trials
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General Information
Disease Group:ColorectalSupported By:N/A
Phase of Study:Phase IIIReturn
Visit:
Twice during the first year. After that once a year for 4 more years.
Treatment
Agents:
CelecoxibHome Care:None required
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
No Hospitalization is required
Description/
Intervention:
The goal of this clinical research study is to check your blood to learn if you
have a genetic mutation that your child could inherit. If you have the genetic
mutation, then your child will also have blood drawn in the main study to look
for the genetic change that causes FAP.
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Study Objectives / Outcomes
Primary Objective
To compare the time from randomization to treatment failure over a five year period for subjects treated with celecoxib versus subjects treated with placebo, where treatment failure is defined as the earliest occurrence of one or more of the following:
a. Appearance of >/= 20 polyps (> 2 mm in size) at any colonoscopy during the study, or
b. Diagnosis of colorectal malignancy

Secondary Objectives
· To compare in the ITT population the time from randomization to treatment failure for subjects treated with celecoxib versus placebo, where treatment failure is defined as the earliest occurrence of one or more of the following:
    a. Appearance of >/= 20 polyps (> 2 mm in size) at any colonoscopy during the study, or
    b. Diagnosis of colorectal malignancy, or
    c. Treatment related dropout
  • To compare between subjects treated with celecoxib versus subjects treated with placebo the total number of colorectal polyps (> 2 mm in size) detected over years 1-5 cumulatively
  • To compare colorectal polyp burden over 5 years for subjects treated with celecoxib versus subjects treated with placebo. The polyp burden is defined as the sum of the largest diameters of all polyps (> 2 mm in size) over Years 1-5 cumulatively

Other Objectives
  • Colorectal adenomas: To evaluate histopathological changes for subjects treated with celecoxib vs subjects treated with placebo
  • To characterize the pharmacokinetics of celecoxib in approximately 40 FAP subjects using population compartmental model-based methodologies – PK sites
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Study Status Information
Study Activation / Registration Date:08/30/2006
IRB Review and Approval Date:05/17/2006
Study Type:Phase Iii
Recruitment Status:Open
Projected Accrual:200
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Confirmed diagnosis of non-attenuated FAP based on central genetic testing

2) Male or female subjects aged 10 to 17 years inclusive at the time of enrollment

3) Subject's parent or legal guardian has provided written informed consent prior to enrollment in this study

4) Subject has assented to participate prior to enrollment in this study

5) Subject and parent/legal guardian, agree to comply with study requirements and are able to be at the clinic for all required study visits

6) Willingness to abstain from the chronic use of NSAIDs (including aspirin, selective COX-2 inhibitors), oral adrenocorticosteroids, and other nonsteroidal OTC products for the duration of the study. Chronic use of NSAIDs is defined as a frequency of 1 week (7 consecutive days) for more than 3 weeks per year

7) If subject is female and of childbearing potential, she must meet all of the following conditions: · Have been using adequate contraception (e.g. abstinence, condom, IUD, birth control pill, diaphragm and spermicide foam/gel/cream/suppository combination) since her last menses AND · Be willing to use adequate contraception (as above) during the study AND · Not be breastfeeding AND · (continue # 8)

8) (Continue # 7) Have a negative urine or serum pregnancy test within 14 days prior to study drug administration. If the central serum pregnancy test results are >14 days prior to study drug administration the test must be repeated. This will be done locally by either serum or urine testing.

9) If subject is male and sexually active he must be willing to use a condom and be instructed that his female partner should be using adequate contraception (e.g. female condom, IUD, sub dermal implant, birth control pill, diaphragm and spermicidal foam/gel/cream/suppository combination)

10) The subject will be allowed to proceed to baseline colonoscopy so long as all of the following laboratory criteria (limits of normal for age as appropriate) are met on Baseline evaluation: · Hemoglobin > 10.0 gm/dl · Platelet count > 100,000/microliter · WBC > 3,000/microliter · ALT < 1.5 x UNL; AST < 1.5 x UNL; Alkaline Phosphatase < 1.5 x UNL; Total Bilirubin < 1.5 x UNL unless the subject has Gilbert's disease for which Total Bilirubin must be less or equal than 2.0xULN (Continue #11)·

11) (Continue #10) • Calculated Creatinine Clearance > 90 mL/min/1.73 • No evidence of proteinuria or hematuria • Cholesterol < 1.5x upper limit of normal • Microalbuminuria </= 23 mg/L • For tests not mentioned specifically, there must be no clinically significan abnormalities that in the opinion of the PI would preclude a subject's safe participation

12) Intact colon

13) Colonoscopy will be performed at baseline according to the description provided in Section 8 Colonoscopy Procedures. To proceed to randomization, the subject must have all of the following: · An assessable colon endoscopically evaluated following an adequate bowel preparation AND · If < 20 polyps (> 2mm in size), all must be removed so as to render the colon polyp-free and thus amenable to serial endoscopic surveillance

14) Systolic and Diastolic Blood Pressure < 95th percentile. All Blood Pressure measurements will be taken according to the description provided in Section 7.4. (Blood Pressure Evaluation). Those subjects with blood pressure measurements within the >/= 90 to < 95th percentile group are eligible for enrollment. These subjects must be managed according to the description in Section 8.14 (Blood Pressure Management)

Exclusion Criteria:1) Diagnosis of attenuated FAP based on central genetic testing

2) History of hypersensitivity to COX-2 inhibitors, sulfonamides, NSAIDs or salicylates

3) Subjects who are not heterozygous for the CYP2C9 variant Ile359Leu (CYP2C9 *3).

4) Use of any dose of NSAIDs or oral adrenocorticosteroids, at any frequency of 3 or more times per week during the three months prior to study entry will require a three-month washout period beginning with the time of last dose. (continue #4)

5) (continue #3) Use of any dose of NSAIDs or oral adrenocorticosteroids, at any frequency of less than 3 times per week during the three months prior to study entry will require a one-month washout period beginning with the time of last dose. If chronic inhaled steroid use is required, the subject agrees to use mometasone. Use of mometasone is not restricted. In countries where mometasone is not available, only fluticasone will be permitted

6) Anticipated need for concurrent use of fluconazole or lithium

7) Active peptic ulcer disease documented by endoscopy. Significant renal, hepatic or hematologic dysfunction (to be determined by investigator). History of H. pylori related peptic ulcer disease that has been successfully treated with antibiotics will not be exclusionary

8) Greater than or equal to 20 polyps (> 2 mm in size) at baseline colonoscopy

9) < 20polyps(> 2 mm in size) that have not all been removed at baseline colonoscopy

10) Known inability to participate in the scheduled follow-up tests

11) Significant medical or psychiatric problems, which, in the opinion of the site investigator, would make the subject a poor protocol candidate

12) Subject has undergone a colectomy or planned to have colectomy within the next 6 months

13) Subject has undergone chemotherapy within the past 6 months

14) Subject has received pelvic radiation

15) History of invasive carcinoma in the past five years

16) Familial hypercholesterolemia

17) Familial Hypertriglyceridemia

18) Diabetes

19) History of coagulopathy that precludes the removal of all polyps

20) Use of any investigational agent within the last 3 months

21) ECG with any findings deemed by the investigator to be clinically significant.

22) Subjects with Inflammatory Bowel Disease

23) Pre-existing renal disease such as glomerulonephritis, nephritic syndrome, renal transplants, or uncorrected renal/bladder obstruction

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Links
Registration Number: NCT00585312
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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