10-Propargyl-10-Deazaaminopterin Plus Probenecid in Treating Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Probenecid may increase the effectiveness of 10-propargyl-10-deazaaminopterin by making tumor cells more sensitive to the drug.
PURPOSE: Phase I trial to study the effectiveness of combining 10-propargyl-10-deazaaminopterin and probenecid in treating patients who have advanced solid tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
OBJECTIVES:
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Determine the maximum tolerated dose of 10-propargyl-10-deazaaminopterin and probenecid in patients with advanced solid tumors.
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Determine the therapeutic activity of this regimen in these patients.
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Determine the toxic effects of this regimen in these patients.
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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.
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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Histologically confirmed cancer that is potentially incurable by standard chemotherapy, radiotherapy, or surgical procedures
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Failed prior first-line therapy (patients are also eligible if no effective first-line therapy exists)
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Previously treated or clinically stable brain metastases are allowed
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No leukemia or lymphoma
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No clinically significant pleural effusions or ascites
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Karnofsky 70-100%
Life expectancy:
- Not specified
Hematopoietic:
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WBC at least 4,000/mm^3
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Platelet count at least 160,000/mm^3
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Hemoglobin greater than 10 g/dL
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Serum and RBC folate normal
Hepatic:
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Bilirubin no greater than 1.5 mg/dL
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SGOT or SGPT less than 2 times upper limit of normal
Renal:
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Creatinine no greater than 1.2 mg/dL OR
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Creatinine clearance at least 60 mL/min
Cardiovascular:
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No unstable angina
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No congestive heart failure
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No cardiac arrhythmia
Other:
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Homocysteine normal
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No grade III or IV edema
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Not pregnant or nursing
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Fertile patients must use effective contraception during and for 6 months after study
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
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See Disease Characteristics
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At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas or mitomycin) and recovered
Endocrine therapy:
- Not specified
Radiotherapy:
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See Disease Characteristics
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At least 3 weeks since prior radiotherapy to bone marrow-containing areas and recovered
Surgery:
-
See Disease Characteristics
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No prior pneumonectomy
Other:
- No concurrent folic acid or potentially nephrotoxic agents
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10021 |
Sponsors and Collaborators
- Memorial Sloan Kettering Cancer Center
- National Cancer Institute (NCI)
Investigators
- Study Chair: Naiyer Rizvi, MD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MSKCC-01014
- CDR0000068905
- NCI-H01-0077