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

University of Maryland Baltimore (UMB)

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Prostate Cancer

Treatments

Drug: tributyrin

Drug: chemotherapy

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00002677

UMCC-9421

NCI-T94-0181O

CDR0000064322 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

24 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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