A Phase I Study of Pemetrexed (LY231514, Alimta) in Children and Adolescents With Recurrent Solid Tumors
1 Year
21 Years
Both
Unspecified Childhood Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of Pemetrexed (LY231514, Alimta) in Children and Adolescents With Recurrent Solid Tumors
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed solid tumor for which there is no known curative therapy or
therapy that is known to prolong survival with acceptable quality of life
- Histologic requirement waived for intrinsic brain stem tumors
- No pleural effusion or ascites
- Neurological deficits from CNS tumors must have been relatively stable for at least 1
week prior to study entry
PATIENT CHARACTERISTICS:
Age
- 1 to 21
Performance status
- Karnofsky 50-100% (over 10 years of age)
- Lansky 50-100% (10 years of age and under)
Life expectancy
- At least 8 weeks
Hematopoietic
- Absolute neutrophil count at least 1,000/mm^3
- Platelet count at least 100,000/mm^3 (transfusion independent)
- Hemoglobin at least 8.0 g/dL (transfusion allowed)
Hepatic
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- ALT no greater than 2.5 times ULN
- Albumin at least 2 g/dL
Renal
- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min OR
- Creatinine based on age as follows:
- No greater than 0.8 mg/dL (age 5 and under)
- No greater than 1.0 mg/dL (age 6 to 10)
- No greater than 1.2 mg/dL (age 11 to 15)
- No greater than 1.5 mg/dL (age 16 and over)
Pulmonary
- No evidence of dyspnea at rest
- No exercise intolerance
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No evidence of Approved-not yet active graft-versus-host disease
- No uncontrolled infection
- Seizure disorder allowed provided it is well-controlled with anticonvulsants
- CNS toxicity no greater than grade 1
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Recovered from prior immunotherapy
- At least 7 days since prior antineoplastic biologic therapy
- At least 6 months since prior allogeneic stem cell transplantation
- More than 1 week since prior growth factors
- No concurrent biologic therapy
- No concurrent immunotherapy
- No concurrent prophylactic growth factor support during course 1
Chemotherapy
- No prior pemetrexed disodium
- More than 3 weeks since prior myelosuppressive chemotherapy (4 weeks for
nitrosoureas) and recovered
- No other concurrent chemotherapy
Endocrine therapy
- Concurrent dexamethasone for CNS tumors allowed provided dose has been stable or
decreasing for at least 1 week prior to study entry
Radiotherapy
- Recovered from all prior radiotherapy
- At least 2 weeks since prior local palliative radiotherapy
- At least 6 months since prior craniospinal radiotherapy
- At least 6 months since prior radiotherapy to 50% or more of the pelvis
- At least 6 weeks since prior substantial bone marrow radiotherapy
- No concurrent radiotherapy
Surgery
- Not specified
Other
- No trimethoprim or sulfa within 2 days before and after study drug administration
- No concurrent nonsteroidal anti-inflammatory agents (e.g., ibuprofen and aspirin)
- No other concurrent anticancer or investigational agents
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
H. Stacy Nicholson, MD, MPH
Investigator Role:
Study Chair
Investigator Affiliation:
OHSU Knight Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000334572
NCT ID:
NCT00070473
Start Date:
October 2003
Completion Date:
Related Keywords:
- Unspecified Childhood Solid Tumor, Protocol Specific
- unspecified childhood solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| 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 |
