| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| FAMILIAL ADENOMATOUS POLYPOSIS (FAP) |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To evaluate the efficacy and safety of celecoxib versus placebo in the prevention and treatment of colorectal polyps growth in young subjects with FAP.
Primary Objective:
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:
a. Appearance of ≥ 20 polyps at any colonoscopy during the study, or
b. Diagnosis of colorectal malignancy |
|
| E.2.2 | Secondary objectives of the trial |
• To compare the total number of polyps over 5 years for subjects treated with celecoxib versus subjects treated with placebo
• To compare polyp burden over 5 years for subjects treated with celecoxib versus
subjects treated with placebo
• To compare celecoxib with placebo on the time to appearance of ≥ 5 colorectal
adenomas for subjects treated with celecoxib versus subjects treated with placebo |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1-Psychosocial Assessment (Version 9-Nov-2006)
2-Pharmacokinetic Analysis (version 9-Nov-2006) (No applicable for Spain)
3-Enhancement colonoscopies (Sites ACF) (No applicable for Spain) |
|
| E.3 | Principal 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/µl
• WBC > 3,000/µl
• 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 ≤ 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 |
|
| E.4 | Principal 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 (> 2 mm without dye enhancement) at baseline colonoscopy
7. < 20polyps(> 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 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Time to treatment failure defined as the time
• The primary endpoint for this study is time to treatment failure defined as the time
from randomization to the earliest occurrence of the following events:
a. Appearance of ≥20 polyps (>2mm, visible without dye enhancement) at any
colonoscopy during the study, or
b. Diagnosis of colorectal malignancy |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Study termination beased on factors such as unacceptable adverse effects, lack of study drug efficacy, or poor accrual. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
Print
