A Phase I Study of Pemetrexed (LY231514, Alimta) in Children and Adolescents With Recurrent Solid Tumors
- 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
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.
Primary Purpose: Treatment
H. Stacy Nicholson, MD, MPH
OHSU Knight Cancer Institute
United States: Federal Government
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Mayo Clinic Cancer Center||Rochester, Minnesota 55905|
|Indiana University Cancer Center||Indianapolis, Indiana 46202-5265|
|University of Mississippi Medical Center||Jackson, Mississippi 39216-4505|
|Children's Hospital Los Angeles||Los Angeles, California 90027-0700|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital of Pittsburgh||Pittsburgh, Pennsylvania 15213|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|Herbert Irving Comprehensive Cancer Center at Columbia University||New York, New York 10032|
|Cancer Institute at Oregon Health and Science University||Portland, Oregon 97201-3098|
|Fairview University Medical Center - University Campus||Minneapolis, Minnesota 55455|
|Stanford Cancer Center at Stanford University Medical Center||Stanford, California 94305|
|SUNY Upstate Medical University Hospital||Syracuse, New York 13210|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas||Dallas, Texas 75390|
|Baylor University Medical Center - Houston||Houston, Texas 77030-2399|
|NCI - Pediatric Oncology Branch||Bethesda, Maryland|