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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00002677
First received: November 1, 1999
Last updated: February 8, 2013
Last verified: April 2001
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: chemotherapy
Drug: tributyrin
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PHASE I STUDY OF THE ORALLY ADMINISTERED BUTYRATE PRODRUG, TRIBUTYRIN, IN PATIENTS WITH SOLID TUMORS

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Enrollment: 24
Study Start Date: August 1995
Primary Completion Date: January 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002677

Locations
United States, Maryland
Marlene & Stewart Greenebaum Cancer Center, University of Maryland
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
Investigators
Study Chair: David A. Van Echo, MD University of Maryland Greenebaum Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00002677     History of Changes
Other Study ID Numbers: CDR0000064322, UMCC-9421, NCI-T94-0181O
Study First Received: November 1, 1999
Last Updated: February 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
stage IV prostate cancer
recurrent prostate cancer
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Prostatic Neoplasms
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on September 11, 2014