A Double-Blind, Randomized, Phase III Trial of the Safety and Efficacy of CPP-1X/Sulindac Compared with CPP-1X, Sulindac as Single Agents in Patients with Familial Adenomatous Polyposis (FAP)
- Conditions
- FAMILIAL ADENOMATOUS POLYPOSISFAP10018018
- Registration Number
- NL-OMON44874
- Lead Sponsor
- Cancer Prevention Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
Subjects (male and female), * 18 years
1. Diagnosis of phenotypic classical FAP with disease involvement of the duodenum and/or colon/rectum/pouch.
a. Genotype: APC mutation (with or without family history) required
b. Classical FAP Phenotype: 100*s to 1,000*s of colorectal adenomatous polyps, usually appearing in teenage years
2. UGI endoscopy/LGI endoscopy (proctoscopy/colonoscopy) performed within 30 days of randomization.
3. Patients with an intact colon/rectum and prophylactic surgery is being considered as a stratification site.
4. Rectal/pouch polyposis as a stratification site as follows:
4.a At least three years since colectomy with IRA/proctocolectomy with pouch, and demonstrating polyposis as defined by Stage 1, 2, 3, of the proposed InSiGHT 2011 Staging System (protocol Appendix B) and summarized as follows:
Stage 1: 10-25 polyps, all < 5 mm
Stage 2: 10-25 polyps, at least one > 1 cm
Stage 3: >25 polyps amenable to complete removal, or any incompletely removed sessile polyp, or any prior evidence of high grade dysplasia, even if completely removed. [Note: For staging purposes only.]
4.b For all subjects, any rectal/pouch polyps > 5 mm must be excised at *baseline*.
5. Duodenal polyposis as a stratification site; one or more of the following:
5.a Current Spigelman Stage 3 or 4. (Refer to protocol Appendix A for Modified Spigelman Score and Classification table).
5.b Prior surgical endoscopic intervention within the past six months for Spigelman Stage 3 or 4 that may have been down staged to Spigelman 1 or 2.
6. Hematopoietic Status (within 30 days prior to randomization):
a) No significant hematologic abnormalities
b) WBC at least 3000/mm3
c) Platelet count at least 100,000/mm3
d) Hemoglobin at least 10.0 g/dL
e) No history of clinical coagulopathy
7. Hepatic Status (within 30 days prior to randomization):
a) Bilirubin no greater than 1.5 times ULN
b) AST and ALT no greater than 1.5 times ULN
c) Alkaline phosphatase no greater than 1.5 times ULN
8. Renal Status (within 30 days prior to randomization):
a) Creatinine no greater than 1.5 times ULN
9. Hearing:
a) No clinically significant hearing loss, defined in Section 6.2, number 9.
10. If female, neither pregnant nor lactating.
11. Negative pregnancy test if female of child-bearing potential. Fertile patients must use effective contraception. Confirmation of postmenopausal status unless surgically sterile.
12. Absence of gross blood in stool; red blood on toilet paper only acceptable.
13. No discrete gastric or duodenal ulcer greater than 5 mm within the past year except Helicobacter pylori-related peptic ulcer disease treated with antibiotics.
14. No invasive malignancy within the past 5 years except resected non-melanomatous skin cancer, papillary thyroid cancer, or precancerous cervical dysplasia.
15. No other significant medical or psychiatric problems that would preclude study participation or interfere with capacity to give informed consent.
16. Use of 81 to 100 mg daily aspirin or up to 700 mg aspirin not more than once a week are eligible.
17. No concurrent warfarin, fluconazole, lithium, Pradaxa® or other direct thrombin inhibitors, Plavix®, cyclosporine, other NSAIDs (such as ibuprofen, aspirin, diflunisal), diuretics (furosemide and thiazides), DMSO, methotrexate, probenecid, propoxyphene hydrochloride, Tylenol® (acetami
1. Prior pelvic irradiation.
2. Patients receiving oral corticosteroids within 30 days of enrollment.
3. Treatment with other investigational agents in the prior 4 weeks.
4. Use of other non-steroidal anti-inflammatory drugs (such as ibuprofen) exceeding 4 days per month, in the prior 6 weeks.
5. Regular use of aspirin in excess of 700 mg per week.
6. Treatment with other FAP directed drug therapy (including sulindac or celecoxib, fish oil) within 12 weeks of study enrollment.
7. Hypersensitivity to cyclooxygenase-2 inhibitors, sulfonamides, NSAIDs, or salicylates; NSAID associated symptoms of gastritis.
8. Patients must not have cardiovascular disease risk factors as defined below.
* Uncontrolled high blood pressure (systolic blood pressure > 150 mm Hg;
* Unstable angina;
* History of documented myocardial infarction or cerebrovascular accident;
* New York Heart Association Class III or IV heart failure (Refer to Appendix C);
* Known uncontrolled hyperlipidemia defined as LDL-C * 190 mg/dL or triglycerides * 500 mg/dL.
9. Patients with significant hearing loss are not eligible for study participation as defined below.
* Hearing loss that affects everyday life and/or for which a hearing aid is required.
10. Colon/rectum/pouch with high grade dysplasia or cancer on biopsy or a large polyp (>1 cm) not amenable to complete removal.
11. Duodenal cancer on biopsy.
12. Intra-abdominal desmoid disease, stage III or IV (staging criteria in protocol Appendix D).
13. Inability to provide informed consent.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Efficacy End Point is the first occurrence of any FAP-related event in<br /><br>the patient as a whole.<br /><br>This includes:<br /><br>1) FAP related excisional intervention involving the colon, rectum, pouch,<br /><br>duodenum and/or<br /><br>2) clinically important events which includes progression to more advanced<br /><br>duodenal polyposis, cancer or death.<br /><br><br /><br>The timepoint(s) of evaluation of this endpoint:<br /><br>Subjects will be assessed at 3, 6, 12, 18, and 24 months. Endoscopies (upper<br /><br>and lower GI) will be carried out every 6 months.<br /><br>For subjects participating in the treatment extension up to 2 additional<br /><br>endosocpies will be performed (month 30 and 36).<br /><br>For subjects participating in the prolonged treatment extension (month 36-48)<br /><br>up to 2 additional endoscopies will be performed (month 42 and 48). </p><br>
- Secondary Outcome Measures
Name Time Method