Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	MSKCC-01014 NCI-H01-0077, NCT00024245

Objectives

1. Determine the maximum tolerated dose of 10-propargyl-10-deazaaminopterin and probenecid in patients with advanced solid tumors.
2. Determine the therapeutic activity of this regimen in these patients.
3. Determine the toxic effects of this regimen in these patients.
4. 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:

• 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

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

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

Expected Enrollment

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.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Naiyer Rizvi, MD, Protocol chair		Ph: 212-639-3204; 800-525-2225

Registry Information
Official Title		Phase I and Clinical Pharamcologic Study of 10-Propargyl-10-Deazaaminopterin (PDX) in Combination with Probenecid in Adults with Advanced Solid Tumors
Trial Start Date		2001-05-21
Registered in ClinicalTrials.gov		NCT00024245
Date Submitted to PDQ		2001-07-26
Information Last Verified		2003-03-28
NCI Grant/Contract Number		CA05826, CA08748

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