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


Phase 1
18 Years
N/A
Not Enrolling
Both
Prostate Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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


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.

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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

David A. Van Echo, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Maryland Greenebaum Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000064322

NCT ID:

NCT00002677

Start Date:

August 1995

Completion Date:

Related Keywords:

  • Prostate Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • stage IV prostate cancer
  • recurrent prostate cancer
  • unspecified adult solid tumor, protocol specific
  • Prostatic Neoplasms
  • Neoplasms

Name

Location

Marlene & Stewart Greenebaum Cancer Center, University of MarylandBaltimore, Maryland  21201