Tributyrin in Treating Patients With Refractory Prostate Cancer or Other Solid Tumors
PHASE I STUDY OF THE ORALLY ADMINISTERED BUTYRATE PRODRUG, TRIBUTYRIN, IN PATIENTS WITH SOLID TUMORS
Study Overview
Status
Intervention / Treatment
Detailed Description
OBJECTIVES:
I. Determine the maximum tolerated dose and optimum schedule of tributyrin in patients with prostate cancer or other solid tumors.
II. Determine the toxic effects of tributyrin in these patients. III. Determine the pharmacodynamics of tributyrin, including modulation of tumor markers, evaluation of clinical remission (when possible), assessment of F-reticulocytes and/or F cells, and evaluation of hemoglobin F before and after treatment, in these patients.
IV. Determine the pharmacokinetics of tributyrin, including maximum plasma concentration, terminal half-life, area under the concentration time curve, volume of distribution, and clearance of butyrate, in these patients.
V. Determine the relationship between the pharmacokinetics and toxic or therapeutic pharmacodynamic effects of butyrate in these patients.
VI. Calculate a tributyrin dose, using results from pharmacokinetic and pharmacodynamic studies, that achieves sustained butyrate concentrations capable of increasing therapeutic effects with reduced toxicity.
OUTLINE: This is a dose escalation study.
Patients receive oral tributyrin every 8 hours for 3 weeks. Treatment continues every 4 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve stable disease may receive additional courses at the discretion of the protocol chairperson. Cohorts of 3-6 patients receive escalating doses of tributyrin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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-
Maryland
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Baltimore, Maryland, United States, 21201
- Marlene & Stewart Greenebaum Cancer Center, University of Maryland
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
- Histologically proven prostate cancer or other solid tumor that is refractory to standard treatment or for which no standard therapy exists
Patients with prostate cancer must meet the following conditions:
- Stage D2 disease
- Disease progression after orchiectomy or treatment with leuprolide or flutamide
- If no prior orchiectomy, must continue leuprolide or other antiandrogen throughout study
- No CNS neoplasms or brain metastases
PATIENT CHARACTERISTICS:
- Age: 18 and over
- Performance status: ECOG 0-2
- Life expectancy: More than 3 months
- WBC at least 3,000/mm3
- Platelet count at least 100,000/mm3
- Hemoglobin at least 9 g/dL
- Bilirubin no greater than 1.5 mg/dL
- AST and ALT no greater than 1.5 times normal
- Creatinine no greater than 1.5 mg/dL OR creatinine clearance greater than 50 mL/min
- No concurrent medical or psychiatric condition that would preclude study
- Able to swallow numerous capsules
- Willing to participate in pharmacokinetic studies
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since prior chemotherapy (more than 8 weeks since prior carmustine, mitomycin, or other drugs with delayed toxic effects) and recovered
- No prior suramin
- At least 4 weeks since prior flutamide
- No concurrent hydrocortisone or other steroids
- At least 4 weeks since prior radiotherapy and recovered
- No concurrent palliative radiotherapy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Arm I
Patients receive oral tributyrin every 8 hours for 3 weeks.
Treatment continues every 4 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
Patients who achieve stable disease may receive additional courses at the discretion of the protocol chairperson.
Cohorts of 3-6 patients receive escalating doses of tributyrin until the maximum tolerated dose (MTD) is determined.
The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
|
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: David A. Van Echo, MD, University of Maryland Greenebaum Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- UMCC-9421
- CDR0000064322 (Registry Identifier: PDQ (Physician Data Query))
- NCI-T94-0181O
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