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Urinary Biomarker Study With Sulindac and Difluoromethylornithine

This study has been withdrawn prior to enrollment.
(Funding and staffing)
Sponsor:
Collaborator:
University of Arizona
Information provided by (Responsible Party):
Patricia Thompson-Carino, University of Arizona
ClinicalTrials.gov Identifier:
NCT01636128
First received: July 2, 2012
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Focus of Study: Drug Response Biomarkers, Chemoprevention, Neoplasms
Drug: difluoromethylornithine
Drug: Sulindac
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: A Phase 2 Urinary Biomarker Study of Polyamine Inhibition With Sulindac and Difluoromethylornithine (DFMO)

Resource links provided by NLM:


Further study details as provided by Cancer Prevention Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Measure intra-subject urine N1-monoacetylspermidine and dcSAM variability during the pre-drug phase [ Time Frame: Week 1-Week 2 ] [ Designated as safety issue: No ]
    Measure initial variability in levels of urinary biomarkers prior to initiation of drug treatment. Three blood draws over the first 14 days will be used to assess baseline variability.

  • Determine dcSAM content of urine after 14 days of 500mg DFMO daily alone [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Measure urinary biomarker dcSAM after 14 days of single agent DFMO. Measure urinary biomarker dcSAM after 14 days of single agent DFMO for treatment arm where DFMO alone is started week 2 (Treatment sequence A).

  • Determine N1-monoacetylspermidine content of urine after 14 days plus 1 day of 150 mg sulindac alone [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Measure urinary biomarker dcSAM after 14 days of single agent sulindac. Measure urinary biomarker dcSAM after 14 days of single agent sulindac for treatment arm where sulindac alone is started week 2 (Treatment sequence B).

  • Determine dcSAM and N1-monoacetylspermidine content of urine after 14 days of 150 mg sulindac daily combined with DFMO at 500 mg/day [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
  • Determine dcSAM content of urine after 14 days of 500mg DFMO daily alone [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Measure urinary biomarker dcSAM after 14 days of single agent DFMO for treatment arm where DFMO alone is started week 10 (Treatment sequence B)

  • Determine N1-monoacetylspermidine content of urine after 14 days plus 1 day of 150 mg sulindac alone [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Measure urinary biomarker dcSAM after 14 days of single agent sulindac. Measure urinary biomarker dcSAM after 14 days of single agent sulindac for treatment arm where sulindac alone is stated week 10 (Treatment sequence A).


Secondary Outcome Measures:
  • Determine if 2 weeks is sufficient time for dcSAM levels and N1-monoacetylspermidine content of urine to recover after stopping DFMO and sulindac [ Time Frame: Week 22 ] [ Designated as safety issue: No ]
  • Determine the length of time it takes for sulindac or DFMO to induce measurable changes in biomarker content of urine [ Time Frame: Week 3-Week 25 ] [ Designated as safety issue: No ]
  • Explore the effect of dietary intake of polyamine measured using the Arizona Food Frequency Questionnaire [ Time Frame: Week 1-25 ] [ Designated as safety issue: No ]
    Quantitate dietary polyamine levels over the course of the study and evaluate the effects on biomarkers evaluated in the primary outcome measures.


Enrollment: 0
Study Start Date: March 2014
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sulindac first (Treatment Sequence B)
Sulindac alone, washout, DFMO alone, then combination of sulindac and DFMO
Drug: difluoromethylornithine
500 mg oral for 14 days, combined with sulindac for 15 days
Other Name: DFMO, eflornithine
Drug: Sulindac
150 mg oral for 15 days, combined with DFMO for 14 days
Experimental: DFMO first (Treatment Sequence A)
DFMO alone, followed by washout, sulindac alone, then combination of DFMO and sulindac
Drug: difluoromethylornithine
500 mg oral for 14 days, combined with sulindac for 15 days
Other Name: DFMO, eflornithine
Drug: Sulindac
150 mg oral for 15 days, combined with DFMO for 14 days

  Eligibility

Ages Eligible for Study:   40 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Patricia Thompson-Carino, Associate Professor, Cellular and Molecular Medicine, University of Arizona
ClinicalTrials.gov Identifier: NCT01636128     History of Changes
Other Study ID Numbers: UA-UB-101
Study First Received: July 2, 2012
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Cancer Prevention Pharmaceuticals, Inc.:
Urinary
biomarkers
DFMO
sulindac

Additional relevant MeSH terms:
Eflornithine
Sulindac
Analgesics
Analgesics, Non-Narcotic
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Antiparasitic Agents
Antiprotozoal Agents
Antirheumatic Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses
Trypanocidal Agents

ClinicalTrials.gov processed this record on November 25, 2014