Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Alternate Title

Phenylbutyrate in Treating Patients With Advanced Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed over 18 NCI MSKCC-94111 NCI-T94-0170D, T94-0170

Objectives

I.  Assess tolerance to and side effects of phenylbutyrate (PBA) in patients 
with advanced cancer receiving twice daily 30-minute infusions, 5 days/week 
for 2 weeks every 28 days.

II.  Estimate the maximum tolerated dose and an appropriate Phase II dose of 
PBA administered on this schedule.

III.  Define the relationships between the administered dose of PBA and the 
plasma concentrations of PBA, phenylacetate, and phenylacetylglutamide, and 
seek evidence of saturability of clearance mechanisms leading to drug 
accumulation on this schedule.

IV.  Assess any antitumor effects of PBA in these patients, and seek evidence 
of drug-induced cytodifferentiation.

Entry Criteria

Disease Characteristics:

Histologically or cytologically diagnosed, unresectable solid tumor, including
primary CNS tumors and lymphomas
  Pathology reviewed at Memorial Hospital

  Progressive after standard therapy or no such therapy available

  Residual or recurrent CNS tumor documented by gadolinium-enhanced MRI or
  contrast-enhanced CT (if MRI contraindicated) within 2 weeks of entry

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  At least 4 weeks since chemotherapy (6 weeks since mitomycin or
     nitrosoureas)
  Recovered from myelosuppressive and gastrointestinal toxicity

Endocrine therapy:
  Not specified

Radiotherapy:
  At least 4 weeks since radiotherapy
  Recovered from myelosuppressive and gastrointestinal toxicity

Surgery:
  Not specified

Patient Characteristics:

Age:
  Over 18

Performance status:
  Karnofsky 50-100% (ECOG 0-2)

Life expectancy:
  At least 4 months (3 months for primary CNS tumors)

Hematopoietic:
  WBC at least 2,500
  AGC at least 1,000
  Platelets at least 100,000
  Hb at least 9 g/dl

Hepatic:
  Bilirubin no greater than 2 mg/dl
  SGOT no greater than 2 x ULN

Renal:
  Creatinine no greater than 2 mg/dl

Cardiovascular:
  No NYHA class III/IV status

Other:
  No active infection
  No medical/psychiatric contraindication to investigational therapy
  Geographically accessible for follow-up
  No pregnant or nursing women
  Effective contraception required of fertile women

Expected Enrollment

20-25 patients will be entered over 15-18 months.

Outline

Single-Agent Chemotherapy.  Phenylbutyrate, PBA, NSC-657802.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Charles W. Young, MD, Protocol chair(Contact information may not be current)		Ph: 212-639-7940; 800-525-2225 Email: youngc@mskcc.org