10-Propargyl-10-Deazaaminopterin Plus Probenecid in Treating Patients With Advanced Solid Tumors
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Unspecified Adult Solid Tumor, Protocol Specific
Intervention: 10-propargyl-10-deazaaminopterin (Drug); probenecid (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Memorial Sloan-Kettering Cancer Center Official(s) and/or principal investigator(s):
Naiyer Rizvi, MD, Study Chair, Affiliation: Memorial Sloan-Kettering Cancer Center
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.
Clinical Details
Official title: Phase I and Clinical Pharamcologic Study of 10-Propargyl-10-Deazaaminopterin (PDX) in Combination With Probenecid in Adults With Advanced Solid Tumors
Study design: Treatment
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: May 2001
Last updated: May 23, 2008
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