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

October 31, 2019 updated by: University of Maryland, Baltimore

PHASE I STUDY OF THE ORALLY ADMINISTERED BUTYRATE PRODRUG, TRIBUTYRIN, IN PATIENTS WITH SOLID TUMORS

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.

Study Overview

Status

Completed

Conditions

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

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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.
Drug: chemotherapy
Drug: tributyrin

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Maryland, Baltimore

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: David A. Van Echo, MD, University of Maryland Greenebaum Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 1995

Primary Completion (Actual)

March 1, 2003

Study Completion (Actual)

March 1, 2003

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

May 10, 2004

First Posted (Estimate)

May 11, 2004

Study Record Updates

Last Update Posted (Actual)

November 4, 2019

Last Update Submitted That Met QC Criteria

October 31, 2019

Last Verified

October 1, 2019

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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