Phase I Study of 10-Propargyl-10-Deazaaminopterin and Probenecid in Patients With Advanced Solid Tumors
Alternate Title Basic Trial Information Objectives Entry Criteria Projected Accrual Outline Trial Contact Information
Alternate Title
10-Propargyl-10-Deazaaminopterin Plus Probenecid in Treating Patients With Advanced Solid Tumors
Basic Trial Information
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Type
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Status
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Age
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Sponsor
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Protocol IDs
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Phase I
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Treatment
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Completed
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18 and over
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NCI
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MSKCC-01014 NCI-H01-0077
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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.
Entry 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
Prior/Concurrent Therapy:
Biologic therapy: Chemotherapy: - See Disease Characteristics
- At least 3 weeks since prior chemotherapy (4 weeks for
nitrosoureas or mitomycin) and recovered
Endocrine therapy: 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
Patient Characteristics:
Age: Performance status: Life expectancy: Hematopoietic: - WBC at least 4,000/mm3
- Platelet count at least 160,000/mm3
- 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
Projected Accrual A total of 35-40 patients will be accrued for this study. 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. Disclaimer The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.
Trial Contact Information
Trial Lead Organizations Memorial Sloan-Kettering Cancer Center | | | Naiyer Rizvi, MD, Protocol chair | | | | Back to Top |