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

Memorial Sloan Kettering Cancer Center

Overview

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.

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.

Study Type

INTERVENTIONAL

Purpose

TREATMENT

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Interventions

pralatrexateDRUG

probenecidDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Data from ClinicalTrials.gov

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