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

NCT ID: NCT00024245

Last Updated: 2013-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-05-31
• Study Completion Date: 2003-04-30

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.

Detailed Description

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Primary Study Purpose: TREATMENT

Interventions

pralatrexate

Intervention Type: DRUG

probenecid

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

Naiyer Rizvi, MD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

CDR0000068905

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-H01-0077

Identifier Type: -

Identifier Source: secondary_id

MSKCC-01014

Identifier Type: -

Identifier Source: org_study_id