Clinical trial NCT01636128: Urinary Biomarker Study With Sulindac and Difluoromethylornithine
Official title: A Phase 2 Urinary Biomarker Study of Polyamine Inhibition With Sulindac and Difluoromethylornithine (DFMO)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Focus of Study: Drug Response Biomarkers, Chemoprevention, Neoplasms
Keywords: Urinary
biomarkers
DFMO
sulindac
Lead sponsor: Cancer Prevention Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: University of Arizona
First posted: 2012-07-10
Enrollment: 0
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to determine the effects of 2 drugs (sulindac and Difluoromethylornithine (DFMO)) either alone or in combination on biomarkers found in urine.


Eligibility criteria: Inclusion Criteria:

* Age 40-65 years
* Fluent in English
* PS 0 ECOG
* Must be able to discontinue the use of aspirin, aspirin containing products, and other non-steroidal anti-inflammatory agents for the duration of the study agent administration period
* Negative fecal occult blood test
* Hemoglobin \> 10g/dl, WBC must be \>4,000 mm3, platelets must be \> 100,000/mm3
* Serum creatinine must be \< 1.5 m/dl
* Serum bilirubin must be \< 2.0 mg/dl, AST and ALT must be \< 1.5x upper limit of normal range
* Female participants must be postmenopausal (at least 1 year since the last menstrual period), surgically sterilized, or willing to use an effective birth control method (e.g., hormonal contraceptive, oral contraceptives, intrauterine device, diaphragm with spermicide, or abstinence) for the duration of the study. Male subjects must use an effective method of birth control throughout the duration of the study and should not impregnate a female.
* Females of childbearing potential must have a negative serum pregnancy test prior to the start of study medication.
* Able to give signed, written informed consent

Exclusion Criteria:

* Requires corticosteroids or nonsteroidal anti-inflammatory agents
* Individuals who are immunosuppressed by virtue of medication or disease. This includes participants known to have AIDS, subjects taking oral steroids, and subjects on immunosuppressants/immunomodulators (cyclosporine, chemotherapeutic agents, or biologic therapy)
* Current use of phenytoin or sulfonamides
* Current or recent (within 3 months) use of coumadin or other systemic anticoagulants.
* Frequently, chronic or moderate/severe gastric complaints. Upper gastrointestinal problems requiring prescription or nonprescription medical remedies for symptoms of heartburn, dyspepsia, nausea, or abdominal pain \> once per week on average
* History of peptic ulcer, occult or gross intestinal bleeding
* Known intercurrent illness, including but no limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, renal disease, liver disease, ongoing or active infection, psychiatric illness, or other situations that would limit compliance or interfere with the ability to comply with the study regimen.
* History of bleeding or clotting disorders
* Individuals with seizures or history of seizures
* History of abnormal wound healing or repair, or conditions that predisposes to the same including diabetes
* Unwilling or unable to limit alcohol consumption to 2-3 servings per week during the study period (12oz beer, 1 oz per alcoholic beverage, 6 oz per wine)
* Individuals enrolled in or who plan to enroll in a clinical intervention trial. There must be a 30 day period between completing a previous study and enrolling in this study.
* Pregnant or lactating women
* Prior DFMO exposure
* History of allergic reaction (e.g., urticaria, asthma, rhinitis) or gastric intolerance attributed to NSAIDs

Primary outcomes:
measure: Measure intra-subject urine N1-monoacetylspermidine and dcSAM variability during the pre-drug phase
timeFrame: Week 1-Week 2
measure: Determine dcSAM content of urine after 14 days of 500mg DFMO daily alone
timeFrame: Week 4
measure: Determine N1-monoacetylspermidine content of urine after 14 days plus 1 day of 150 mg sulindac alone
timeFrame: Week 4
measure: Determine dcSAM and N1-monoacetylspermidine content of urine after 14 days of 150 mg sulindac daily combined with DFMO at 500 mg/day
timeFrame: Week 20
measure: Determine dcSAM content of urine after 14 days of 500mg DFMO daily alone
timeFrame: Week 12
measure: Determine N1-monoacetylspermidine content of urine after 14 days plus 1 day of 150 mg sulindac alone
timeFrame: Week 12
Secondary outcomes:
measure: Determine if 2 weeks is sufficient time for dcSAM levels and N1-monoacetylspermidine content of urine to recover after stopping DFMO and sulindac
timeFrame: Week 22
measure: Determine the length of time it takes for sulindac or DFMO to induce measurable changes in biomarker content of urine
timeFrame: Week 3-Week 25
measure: Explore the effect of dietary intake of polyamine measured using the Arizona Food Frequency Questionnaire
timeFrame: Week 1-25
Other outcomes:
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