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A Phase I Study of Pemetrexed (LY231514, Alimta) in Children and Adolescents With Recurrent Solid Tumors

Phase 1
1 Year
21 Years
Not Enrolling
Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

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.

Inclusion Criteria


- 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



- 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


- 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)


- 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


- 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)


- No evidence of dyspnea at rest

- No exercise intolerance


- 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


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


- 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


- 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


- Not specified


- 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:


Study Design:

Primary Purpose: Treatment

Principal Investigator

H. Stacy Nicholson, MD, MPH

Investigator Role:

Study Chair

Investigator Affiliation:

OHSU Knight Cancer Institute


United States: Federal Government

Study ID:




Start Date:

October 2003

Completion Date:

Related Keywords:

  • Unspecified Childhood Solid Tumor, Protocol Specific
  • unspecified childhood solid tumor, protocol specific
  • Neoplasms



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