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

This study has been completed.
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: September 13, 2001
Last updated: June 25, 2013
Last verified: March 2003

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.

Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: pralatrexate
Drug: probenecid
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I and Clinical Pharamcologic Study of 10-Propargyl-10-Deazaaminopterin (PDX) in Combination With Probenecid in Adults With Advanced Solid Tumors

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: May 2001
Study Completion Date: April 2003
Detailed Description:


  • 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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status:

  • Karnofsky 70-100%

Life expectancy:

  • Not specified


  • 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


  • Bilirubin no greater than 1.5 mg/dL
  • SGOT or SGPT less than 2 times upper limit of normal


  • Creatinine no greater than 1.2 mg/dL OR
  • Creatinine clearance at least 60 mL/min


  • No unstable angina
  • No congestive heart failure
  • No cardiac arrhythmia


  • 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


Biologic therapy:

  • Not specified


  • See Disease Characteristics
  • At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy:

  • Not specified


  • See Disease Characteristics
  • At least 3 weeks since prior radiotherapy to bone marrow-containing areas and recovered


  • See Disease Characteristics
  • No prior pneumonectomy


  • No concurrent folic acid or potentially nephrotoxic agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00024245

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
Study Chair: Naiyer Rizvi, MD Memorial Sloan Kettering Cancer Center
  More Information Identifier: NCT00024245     History of Changes
Other Study ID Numbers: MSKCC-01014  CDR0000068905  NCI-H01-0077 
Study First Received: September 13, 2001
Last Updated: June 25, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Uricosuric Agents
Gout Suppressants
Antirheumatic Agents
Renal Agents processed this record on October 27, 2016