10-Propargyl-10-Deazaaminopterin Plus Probenecid in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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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. 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.

Official Title
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Phase I and Clinical Pharamcologic Study of 10-Propargyl-10-Deazaaminopterin (PDX) in Combination With Probenecid in Adults With Advanced Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: pralatrexate
* Drug: probenecid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: pralatrexate|nan|
|Drug: probenecid|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific