Phase I and Clinical Pharamcologic Study of 10-Propargyl-10-Deazaaminopterin (PDX) in Combination With Probenecid in Adults With Advanced Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
Phase I and Clinical Pharamcologic Study of 10-Propargyl-10-Deazaaminopterin (PDX) in Combination With Probenecid in Adults With Advanced Solid Tumors
OBJECTIVES:
- Determine the maximum tolerated dose of 10-propargyl-10-deazaaminopterin and probenecid
in patients with advanced solid tumors.
- Determine the therapeutic activity of this regimen in these patients.
- Determine the toxic effects of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
OUTLINE: This is a dose-escalation study of 10-propargyl-10-deazaaminopterin (PDX) and
probenecid.
Patients receive probenecid IV and PDX IV on day 1. Treatment repeats every 2 weeks in the
absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive sequentially escalating doses of probenecid and PDX until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of
6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A total of 35-40 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed cancer that is potentially incurable by standard
chemotherapy, radiotherapy, or surgical procedures
- Failed prior first-line therapy (patients are also eligible if no effective
first-line therapy exists)
- Previously treated or clinically stable brain metastases are allowed
- No leukemia or lymphoma
- No clinically significant pleural effusions or ascites
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Karnofsky 70-100%
Life expectancy:
- Not specified
Hematopoietic:
- WBC at least 4,000/mm^3
- Platelet count at least 160,000/mm^3
- Hemoglobin greater than 10 g/dL
- Serum and RBC folate normal
Hepatic:
- Bilirubin no greater than 1.5 mg/dL
- SGOT or SGPT less than 2 times upper limit of normal
Renal:
- Creatinine no greater than 1.2 mg/dL OR
- Creatinine clearance at least 60 mL/min
Cardiovascular:
- No unstable angina
- No congestive heart failure
- No cardiac arrhythmia
Other:
- Homocysteine normal
- No grade III or IV edema
- Not pregnant or nursing
- Fertile patients must use effective contraception during and for 6 months after study
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- See Disease Characteristics
- At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas or mitomycin) and
recovered
Endocrine therapy:
- Not specified
Radiotherapy:
- See Disease Characteristics
- At least 3 weeks since prior radiotherapy to bone marrow-containing areas and
recovered
Surgery:
- See Disease Characteristics
- No prior pneumonectomy
Other:
- No concurrent folic acid or potentially nephrotoxic agents
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Naiyer Rizvi, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Federal Government
Study ID:
MSKCC-01014
NCT ID:
NCT00024245
Start Date:
May 2001
Completion Date:
April 2003
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
