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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00024245
First received: September 13, 2001
Last updated: June 25, 2013
Last verified: March 2003
  Purpose

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:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00024245

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Naiyer Rizvi, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov 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:
Neoplasms
Probenecid
10-deazaaminopterin
Aminopterin
Uricosuric Agents
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Renal Agents
Antineoplastic Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014