Tributyrin in Treating Patients With Refractory Prostate Cancer or Other Solid Tumors

NCT ID: NCT00002677

Last Updated: 2019-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1995-08-31
• Study Completion Date: 2003-03-31

Brief Summary

Phase I trial to study the effectiveness of tributyrin in treating patients with refractory stage IV prostate cancer or other solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

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.

Conditions

Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

chemotherapy

Intervention Type: DRUG

tributyrin

Intervention Type: DRUG

Interventions

chemotherapy

Intervention Type: DRUG

tributyrin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David A. Van Echo, MD

Role: STUDY_CHAIR

University of Maryland Greenebaum Cancer Center

Locations

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

CDR0000064322

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-T94-0181O

Identifier Type: -

Identifier Source: secondary_id

UMCC-9421

Identifier Type: -

Identifier Source: org_study_id