Dettagli per singolo studio

DEC-NET Serial number ES603

Published online	18/10/2006 15.48.00
Last updated	18/10/2006 15.47.07

Other protocol ID number	A3191193
Current trial status	Planned (i.e. not yet recruiting participants)
Major Disease (ICD9 class)	PSEUDOPOLYPOSIS OF COLON
Experimental drug
Celecoxib Treatment regimen (dosage and duration) The dose of celecoxib will depends on the body weigh and will be 16 mg/kg/day for a maximum of 5 years.
Gender	Both
Age (range)	10-17 years old
Eligibility criteria
Inclusion criteria
1. Confirmed diagnosis of FAP based on genetic predisposition 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 gel combination) since her last menses AND - Be willing to use adequate contraception (as above) during the study AND - Not be breastfeeding AND - Have a negative urine or serum pregnancy test within 14 days prior to study drug administration 8. The subject will be allowed to proceed to baseline colonoscopy so long as all of the following laboratory criteria are met on Baseline evaluation: - Hemoglobin > 10.0 gm/dl - Platelet count > 100,000/ml - WBC > 3,000/ml - ALT < 1.5 x upper limit of normal; AST < 1.5 x upper limit of normal - Alkaline Phosphatase < 1.5 x upper limit of normal - Total Bilirubin < 1.5 x upper limit of normal unless the subject has Gilbert.s disease for which Total Bilirubin must be < or = 2.0xULN - Creatinine < 1.5 x upper limit of normal - Cholesterol < 1.5 x upper limit of normal For tests not mentioned specifically, there must be no clinically significant abnormalities that in the opinion of the PI would preclude a subject.s safe participation. 9. Intact colon 10. Colonoscopy will be performed at baseline according to the description provided in Section 9. To proceed to randomization, the subject must have all of the following: - An assessable colon endoscopically evaluated following an adequate preparative procedure (described in Section 9.1) AND - If < 20 polyps (> 2mm, visible without dye-enhancement), all must be removed so as to render the colon polyp-free and thus amenable to serial endoscopic surveillance 11. A normal electrocardiogram (ECG) at baseline . Subjects who have an abnormal tracing that is considered not clinically significant by the site investigator may be entered with sponsor approval.
Exclusion criteria
1. Diagnosis of attenuated FAP 2. History of hypersensitivity to COX-2 inhibitors, sulfonamides, NSAIDs or salicylates 3. 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. 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 were mometasone is not available, only fluticasone will be permitted 4. Anticipated need for concurrent use of fluconazole or lithium 5. 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 6. 20 polyps or more (> 2 mm without dye enhancement) at baseline colonoscopy 7. < 20 polyps (> 2 mm without dye enhancement) that have not all been removed at baseline colonoscopy 8. Known inability to participate in the scheduled follow-up tests 9. Significant medical or psychiatric problems, which, in the opinion of the site investigator, would make the subject a poor protocol candidate 10. Subject has undergone a colectomy or planned to have colectomy within the next 6 months 11. Subject has undergone chemotherapy within the past 6 months 12. Subject has received pelvic radiation 13. History of invasive carcinoma in the past five years 14. Familial hypercholesterolemia 15. Familial Hypertriglyceridemia 16. Diabetes 17. Coagulopathy 18. Use of any investigational agent within the last 3 months
Trial design/methodology
Phase	3
Kind of study	Efficacy Safety
Design	Controlled Randomised Blinded
Purpose of study
The objective of this study is to evaluate the efficacy and safety of celecoxib versus placebo in the prevention and treatment of colorectal polyps. growth in young subjects with FAP. To compare the time from randomization to treatment failure 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: - Appearance of 20 polyps or more at any colonoscopy during the study, or - Diagnosis of colorectal malignancy
Primary outcomes
· In this study, the main outcome is the time until treatment failure, defined as the time between randomisation and the first appearance of the following events: a. Appearance of 20 polyps or more (> 2 mm without dye enhancement) at any colonoscopy during the study, or b. Diagnosis of colorectal malignancy
Secondary outcomes
. Number of colorectal polyps: Total number of colorectal polyps (>2 mm, without dye enhancement) detected from year 1 until year 5 (accumulated) . Charge of colorectal polyps: The charge of colorectal polyps is defined as the addition of the maximum diameters of all the detected polyps from year 1 until year 5 (accumulated) . Time until the appearance of at least 5 colorectal adenomas (>2 mm, without dye enhancement) after adding all the observed periods of visits
Summary of study design, objectives, and ongoing research findings
This is a phase III, double-blind, randomized, placebo-controlled, multicenter trial in subjects with FAP. The study is designed to compare efficacy and safety of celecoxib versus placebo over a 5-year treatment period. Approximately 200 eligible subjects with FAP from multiple international centers will be randomized in a 1:1 ratio to receive either celecoxib (approximately 16 mg/kg/day), or matching placebo for up to 5 years. The objective of this study is to evaluate the efficacy and safety of celecoxib versus placebo in the prevention and treatment of colorectal polyps. growth in young subjects with FAP.