Pemetrexed Disodium in Treating Young Patients With Recurrent Solid Tumors
RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium, use different ways to stop tumor cells from dividing so they stop growing or die. Pemetrexed disodium may stop the growth of tumor cells by blocking the enzymes necessary for their growth.
PURPOSE: This phase I trial is studying the side effects and best dose of pemetrexed disodium in treating young patients with recurrent solid tumors.
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: pemetrexed disodium
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Phase I Study of Pemetrexed (LY231514, Alimta) in Children and Adolescents With Recurrent Solid Tumors|
- Event Free Survival [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]
- Dose Limiting Toxicity [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]Any patient who experiences DLT at any time during protocol therapy will be considered evaluable for toxicity. Patients not experiencing DLT must complete a full cycle of therapy to be considered potentially evaluable for toxicity. Patients who are not evaluable for toxicity will be replaced.
- Maximum Tolerated Dose [ Time Frame: Length of study ] [ Designated as safety issue: No ]The MTD will be that dose at which fewer than one-third of patients experience DLT
|Study Start Date:||October 2003|
|Study Completion Date:||June 2008|
|Primary Completion Date:||March 2006 (Final data collection date for primary outcome measure)|
- Determine the maximum tolerated dose of pemetrexed disodium in children and adolescents with refractory solid tumors.
- Determine the dose-limiting toxic effects of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Determine, preliminarily, the antitumor activity of this drug in these patients.
- Correlate the presence of the C677T polymorphism of the methylenetetrahydrolate reductase gene, the presence of a polymorphism in the enhancer region of the thymidylate synthase (TS) gene promoter (2R and 3R tandem repeats), the presence of a polymorphism within one of those repeats, and the presence of a functional polymorphism in the 3'-untranslated region with toxicity in patients treated with this drug.
- Correlate homocysteine and methylmalonic acid levels at study entry with toxicity in patients treated with this drug.
- Correlate various gene expression profiles with response in patients treated with this drug.
OUTLINE: This is a dose-escalation study.
Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of pemetrexed disodium until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00070473
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 323669|
|Stanford Cancer Center at Stanford University Medical Center|
|Stanford, California, United States, 94305|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010-2970|
|United States, Indiana|
|Indiana University Cancer Center|
|Indianapolis, Indiana, United States, 46202-5289|
|United States, Maryland|
|NCI - Pediatric Oncology Branch|
|Bethesda, Maryland, United States, 301496|
|United States, Massachusetts|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Minnesota|
|Fairview University Medical Center - University Campus|
|Minneapolis, Minnesota, United States, 55455|
|Mayo Clinic Cancer Center|
|Rochester, Minnesota, United States, 55905|
|United States, Mississippi|
|University of Mississippi Medical Center|
|Jackson, Mississippi, United States, 39216-4505|
|United States, New York|
|Herbert Irving Comprehensive Cancer Center at Columbia University|
|New York, New York, United States, 10032|
|SUNY Upstate Medical University Hospital|
|Syracuse, New York, United States, 13210|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229-3039|
|United States, Oregon|
|Cancer Institute at Oregon Health and Science University|
|Portland, Oregon, United States, 97239-3098|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 215590|
|Children's Hospital of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Texas|
|Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas|
|Dallas, Texas, United States, 75390|
|Baylor University Medical Center - Houston|
|Houston, Texas, United States, 832822|
|United States, Washington|
|Children's Hospital and Regional Medical Center - Seattle|
|Seattle, Washington, United States, 206987|
|Hospital for Sick Children|
|Toronto, Ontario, Canada|
|Hopital Sainte Justine|
|Montreal, Quebec, Canada|
|Study Chair:||H. Stacy Nicholson, MD, MPH||OHSU Knight Cancer Institute|
|Study Chair:||Linda C. Stork, MD||Doernbecher Children's Hospital at Oregon Health and Science University|