Phase 1
N=27
Pralatrexate and Fluorouracil in Treating Patients With Recurrent Solid Tumors
Unspecified Adult Solid Tumor, Protocol Specific
Bottom Line
View on ClinicalTrials.gov: NCT01206465 ↗Enrolled (actual)
27
Serious AEs
37.0%
Results posted
Jul 2018
Primary outcome: Primary: Recommended Dose of PDX Given With a Fixed Dose of 5-FU — 148 mg per meter square
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- pralatrexate (Drug); fluorouracil (Drug); laboratory biomarker analysis (Other); DNA analysis (Genetic); high performance liquid chromatography (Other); polymerase chain reaction (Genetic); nucleic acid sequencing (Genetic); pharmacological study (Other); pharmacogenomic studies (Other); polymorphism analysis (Genetic)
- Age
- Adult, Older Adult · 19+ yrs
- Sex
- All
- Sponsor
- University of Nebraska
- Primary completion
- Feb 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Recommended Dose of PDX Given With a Fixed Dose of 5-FU |
148 | — |
| SECONDARY Response to Therapy in Subjects With Measurable Disease |
0; 18; 9 | — |
| SECONDARY Number of Patients Experiencing Grade 3-4 Toxicity While Receiving the Combination of PDX and 5-FU |
4; 0; 4; 1; 5; 1 | — |
| SECONDARY Pharmacokinetics of PDX- AUClast |
12,818; 16300; 15680; 23570; 42121 | — |
| SECONDARY Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase |
51.9; 40.7; 7.4; 55.6; 37.0; 7.4 | — |
| SECONDARY 5-FU Plasma Levels |
1147; 1159; 1123; 1113 | — |
| SECONDARY Time to Disease Progression |
112 | — |
Summary
RATIONALE: Pralatrexate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pralatrexate together with fluorouracil may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of pralatrexate when given together with fluorouracil in treating patients with recurrent solid tumors
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01206465). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.