A Phase I Clinical Trial of Sequential Pralatrexate Followed by a 48-hour Infusion of 5- Fluorouracil Given Every Other Week in Adult Patients With Solid Tumors
19 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Clinical Trial of Sequential Pralatrexate Followed by a 48-hour Infusion of 5- Fluorouracil Given Every Other Week in Adult Patients With Solid Tumors
PRIMARY OBJECTIVES:
I. To determine the recommended dose of PDX (pralatrexate) given in combination with a fixed
dose of 5-FU (fluorouracil) administered as a 48-hour infusion given every other week.
SECONDARY OBJECTIVES:
I. To assess clinical response to therapy in subjects with measurable disease and time to
disease progression in all subjects.
II. To assess the toxicity profile of the combination of PDX and 5-FU. III. To determine the
pharmacokinetics of PDX and 5-FU and correlate with clinical toxicity.
IV. To analyze polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase
(TS) and correlate with clinical toxicity.
OUTLINE: This is a dose-escalation study of pralatrexate.
Patients receive pralatrexate intravenously (IV) over 5 minutes on day 1 and fluorouracil IV
continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of
disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Inclusion Criteria:
- Cancer patients who have failed standard therapy for their disease or for whom no
such therapy is available are eligible, for which 5-fluoropyrimdines, including 5-FU,
or inhibitors of DHFR (dihydrofolate reductase), including pralatrexate, have the
potential for therapeutic benefit
- Objectively measurable disease is preferred, but not required
- Performance status of 0-2 (Eastern Cooperative Oncology Group [ECOG])
- Prior treatment:
- The patient should have recovered from the toxicities associated with prior
chemotherapy (at least 3 weeks from prior therapy)
- At least two or more weeks should have elapsed since any radiotherapy, and the
patient should have recovered from the toxicity associated with such therapy
- If a recent surgical procedure has been performed, the patient should have recovered
from the surgery prior to entering this trial
- Absolute granulocyte count of 1500 per mcL or greater
- Platelet count of 100,000 per mcL or greater
- Serum bilirubin less than 1.5 times the upper limits of the institutional normal
- Serum creatinine less than the upper limits of normal
- The patient must willingly give signed informed consent
Exclusion Criteria:
- Pregnant women and nursing mothers are ineligible; eligible patients of reproductive
potential should use adequate contraception if sexually active
- Serious concurrent medical illness which would jeopardize the ability of the patient
to receive the chemotherapy program outlined in this protocol with reasonable safety
- Patients with active infections requiring intravenous antibiotic therapy are not
eligible until the infection has resolved
- Patients who are human immunodeficiency virus (HIV) antibody positive and are
receiving highly active antiretroviral therapy (HAART) are ineligible
- Concomitant administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and
trimethoprim/sulfamethoxazole will not be allowed
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Recommended dose of PDX given in combination with a fixed dose of 5-FU administered as a 48-hour infusion given every other week
Outcome Description:
Maximum tolerated dose will have been exceeded when 2 patients entered at a given dose level experience specified dose-limiting toxicities in the initial cycle.
Outcome Time Frame:
During the initial course
Safety Issue:
Yes
Principal Investigator
Jean Grem
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Nebraska
Authority:
United States: Institutional Review Board
Study ID:
238-10
NCT ID:
NCT01206465
Start Date:
September 2010
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- Neoplasms
Name | Location |
|---|---|
| UNMC Eppley Cancer Center at the University of Nebraska Medical Center | Omaha, Nebraska 68198-7680 |
