Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00005557

Trial Description

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Title

Phase III Trial of the Safety and Efficacy of Eflornithine Combined With Sulindac Compared to Eflornithine, Sulindac as Single Agents in Patients With Familial Adenomatous Polyposis

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

The purpose of this randomized, double-blind, Phase III trial is to determine if the
combination of eflornithine plus sulindac is superior to sulindac or eflornithine as single
agents in delaying time to the first occurrence of any FAP-related event. This includes: 1)
FAP related disease progression indicating the need for 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.

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Brief Summary in Scientific Language

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Organizational Data

  •   DRKS00005557
  •   2014/08/22
  •   2011/11/21
  •   no
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Secondary IDs

  •   NCT01483144  (ClinicalTrials.gov)
  •   CPP-FAP-310  (Cancer Prevention Pharmaceuticals, Inc.)
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Health Condition or Problem studied

  •   Familial Adenomatous Polyposis
  •   D12 -  Benign neoplasm of colon, rectum, anus and anal canal
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Interventions/Observational Groups

  •   Drug: Eflornithine plus Sulindac
  •   Drug: Eflornithine and Placebo
  •   Drug: Sulindac and Placebo
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, caregiver, investigator/therapist
  •   Active control
  •   Treatment
  •   Parallel
  •   III
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Primary Outcome

- Delaying time to the 1st occurrence of any FAP-related event.; time frame: 24 months from the start of treatment

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Secondary Outcome

- presence or absence of an ODC polymorphism; time frame: 24 months from the start of treatment; evaluate the potentially effect modifying properties of an ornithine decarboyxlase (ODC) polymorphism on primary outcome
- excretion of 4 urinary polyamines; time frame: 24 months from the start of treatment; evaluate the potentially effect modifying properties of 4 urinary polyamines on the primary outcome measure

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Countries of Recruitment

  •   United States
  •   Canada
  •   Germany
  •   Netherlands
  •   Spain
  •   United Kingdom
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Locations of Recruitment

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Recruitment

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  •   2013/10/31
  •   150
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

- Diagnosis of phenotypic classical FAP with disease involvement of the duodenum and/or
colon/rectum/pouch.

1. Genotype: APC mutation (with or without family history) required

2. Classical FAP Phenotype: 100's to 1,000's of colorectal adenomatous polyps,
usually appearing in teenage years

- UGI endoscopy/LGI endoscopy (proctoscopy/colonoscopy) performed within 30 days of
randomization.

- Patients with an intact colon/rectum, except for clinical polyposis, and prophylactic
surgery is being considered as a stratification site.

- Rectal/pouch polyposis as a stratification site as follows:

1. 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 (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 evidence of high grade dysplasia, even if completely
removed. [Note: For staging purposes only.]

2. For all subjects, any rectal/pouch polyps > 5 mm must be excised at "baseline".

- Duodenal polyposis as a stratification site; one or more of the following:

1. Current Spigelman Stage 3 or 4. (Refer to Appendix A for Modified Spigelman
Score and Classification table).

2. 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.

- Hematopoietic Status (within 30 days prior to randomization):

1. No significant hematologic abnormalities

2. WBC at least 3,000/mm3

3. Platelet count at least 100,000/mm3

4. Hemoglobin at least 10.0 g/dL

5. No history of clinical coagulopathy

- Hepatic Status (within 30 days prior to randomization):

1. Bilirubin no greater than 1.5 times ULN

2. AST and ALT no greater than 1.5 times ULN

3. Alkaline phosphatase no greater than 1.5 times ULN

- Renal Status (within 30 days prior to randomization):

a) Creatinine no greater than 1.5 times ULN

- Hearing:

a) No clinically significant hearing loss, defined in Section 6.2, number 9.

- If female, neither pregnant nor lactating.

- Negative pregnancy test if female of child-bearing potential. Fertile patients must
use effective contraception*.

- Absence of gross blood in stool; red blood on toilet paper only acceptable.

- No discrete gastric or duodenal ulcer greater than 5 mm within the past year except
Helicobacter pylori-related peptic ulcer disease treated with antibiotics.

- No invasive malignancy within the past 5 years except resected non-melanomatous skin
cancer, papillary thyroid cancer, or precancerous cervical dysplasia.

- No other significant medical or psychiatric problems that would preclude study
participation or interfere with capacity to give informed consent.

- Use of 81-100 mg daily aspirin or up to 700 mg aspirin not more than once a week are
eligible.

- 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® (acetaminophen) preparations containing aspirin
or cytotoxic chemotherapy drugs.

- Willingness to forego concurrent use of supplements containing omega-3 fatty acids,
corticosteroids, non-steroidal anti-inflammatory drugs or other FAP directed drug
therapy.

- Able to provide informed consent and follow protocol requirements.

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Exclusion Criteria

- Prior pelvic irradiation.

- Patients receiving oral corticosteroids within 30 days of enrollment.

- Treatment with other investigational agents in the prior 4 weeks.

- Use of other non-steroidal anti-inflammatory drugs (such as ibuprofen) exceeding 4
days per month, in the prior 6 weeks.

- Regular use of aspirin in excess of 700 mg per week.

- Treatment with other FAP directed drug therapy (including sulindac or celecoxib, fish
oil) within 12 weeks of study enrollment.

- Hypersensitivity to cyclooxygenase-2 inhibitors, sulfonamides, NSAIDs, or
salicylates; NSAID associated symptoms of gastritis.

- 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

- Known uncontrolled hyperlipidemia defined as LDL-C >= 190 mg/dL or triglycerides
>= 500 mg/dL

- Patients with significant hearing loss are not eligible for study participation
defined as hearing loss that affects everyday life and/or for which a hearing aid is
required.

- Colon/rectum/pouch with high grade dysplasia or cancer on biopsy or a large polyp (>1
cm) not amenable to complete removal.

- Duodenal cancer on biopsy.

- Intra-abdominal desmoid disease, stage III or IV

- Inability to provide informed consent.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Cancer Prevention Pharmaceuticals, Inc.
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    • The Cleveland Clinic
    • Carol Burke, M.D. 
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    • Alfred M Cohen, MD 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   2
  •   2014/11/27
* This entry means the parameter is not applicable or has not been set.