Familial Adenomatous Polyposis (FAP)
Conditions
Sponsors
Cancer Prevention Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects (male and female), = 18 years 2. Diagnosis of genotypic and/or phenotypic FAP or AFAP with disease involvement of the duodenum and/or colon/rectum/pouch. o Genotype: APC mutation o Classical FAP Phenotype: 100’s to 1,000’s of colorectal adenomatous polyps, usually appearing in teenage years 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: At least three years since colectomy/proctocolectomy with IRA or pouch, and demonstrating polyposis as defined by Stage 1,2,3 of proposed InSiGHT staging system. 5. Duodenal polyposis as a stratification site; one or more of the following: Current Spigelman Stage 3 or 4. 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. Absence of major cardiac risk factors. 7. Absence of clinically significant hearing loss requiring a hearing aid. 8. Adequate laboratory studies (hematology, chemistry, and urinalysis) at study entry. 9. If female, neither pregnant nor lactating. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 172 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior pelvic irradiation 2. Patients receiving oral corticosteroids within 30 days of enrolment 3. Treatment with other investigational agents within the prior 4 weeks 4. Use of other non-steroidal anti-inflammatory drugs (such as ibuprofen) exceeding 4 days per month, in the prior 6weeks 5. Regular use of aspirin in excess of 700mg 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 at high cardiovascular disease risk are not eligible for study participation 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; • 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. Intact colon/rectum or retained rectum or ileal pouch: a) cancer on biopsy b)high grade dysplasia found on polyp biopsy where the polyp is not completely removed c)a large polyp (>1cm) not completely removed 11. Duodenal cancer on biopsy. 12. Intra-abdominal desmoid disease, stage III or IV.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to determine whether the combination of CPP-1X + sulindac is superior to either treatment individually, sulindac alone or CPP-1X alone, in delaying time to the first occurrence of any FAP-related event in the patient as a whole. This includes: 1) FAP related excisional intervention involving the colon, rectum, pouch, duodenum and/or 2) clinically important events which includes progression to more advanced duodenal polyposis, cancer or death.; Secondary Objective: 1. To evaluate the potentially effect modifying properties of: a. Presence or absence of an ODC polymorphism b. The excretion of 4 urinary polyamines (diacetylspermine, n1-acetylspermidine, n8-acetylspermidine and decarboxylated SAM) Other secondary outcomes : 1. Safety outcomes by analysis of adverse events and laboratory abnormalities. 2. Pharmacokinetic outcomes by evaluating population pharmacokinetics for CPP-1X (eflornithine) and sulindac. 3. Evaluate tissue and dietary polyamine levels. 4. Patient reported quality of life using HRQoL and patient utilities. 5. A pilot evaluation of an FAP-specific assessment, time to first FAP-related beneficent event, will be studied. This will involve analyzing the endoscopic polyposis data for regression of pre-colectomy colorectal polyposis, rectal/pouch polyposis, and regression of duodenal polyposis. 6. An analysis of the components and subgroups included in the primary analysis, and their contribution to the primary outcome. ;Primary end point(s): Primary Efficacy: The primary end-point is the first occurrence of any FAP-related event in the patient as a whole. This includes: 1) FAP related excisional intervention involving the colon, rectum, pouch, duodenum and/or 2) clinically important events which includes progression to more advanc | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy outcomes in this study will include the following: 2. To evaluate the potentially effect modifying properties of: a. Presence or absence of an ODC polymorphism b. The excretion of 4 urinary polyamines (diacetylspermine, n1-acetylspermidine, n8-acetylspermidine and decarboxylated SAM) Other secondary outcomes in this study include the following: 3. Safety outcomes will be assessed by summary analysis of adverse events and clinical laboratory abnormalities. 4. Pharmacokinetic outcomes will be assessed by evaluating the population pharmacokinetics for CPP-1X (eflornithine) and sulindac. 5. Evaluate tissue and dietary polyamine levels. 6. Patient reported quality of life will be evaluated using HRQoL and patient utilities. 7. A pilot evaluation of an FAP-specific assessment, the time to the first FAP-related beneficent event, will be studied. This will involve analyzing the endoscopic polyposis data for regression of pre-colectomy colorectal polyposis, rectal/pouch polyposis, and regression of duodenal polyposis. 8. An analysis of the components and subgroups included in the primary analysis, and their contribution to the primary outcome ; Timepoint(s) of evaluation of this end point: 1. Ongoing over the duration of the study, for DMC meetings, and at the end of the study. 2. At the end of the treatment phase, from the last patient enrolled. 3. PK samples will be collected at the 3 month subject evaluation point. Analysis of all study subjects will be done after the last visit of the last subject. | — |
Countries
Belgium, Canada, Germany, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactAndrew Hadlington
Wessex Pharma Services Ltd.
Outcome results
None listed