Pemetrexed Disodium in Treating Young Patients With Recurrent Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00070473
Recruitment Status : Completed
First Posted : October 7, 2003
Last Update Posted : February 20, 2014
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Unspecified Childhood Solid Tumor, Protocol Specific Drug: pemetrexed disodium Phase 1

Detailed Description:



  • 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Primary Purpose: Treatment
Official Title: A Phase I Study of Pemetrexed (LY231514, Alimta) in Children and Adolescents With Recurrent Solid Tumors
Study Start Date : October 2003
Actual Primary Completion Date : March 2006
Actual Study Completion Date : June 2008

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. Event Free Survival [ Time Frame: Length of study ]

Secondary Outcome Measures :
  1. Dose Limiting Toxicity [ Time Frame: Length of study ]
    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.

  2. Maximum Tolerated Dose [ Time Frame: Length of study ]
    The MTD will be that dose at which fewer than one-third of patients experience DLT

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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): 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
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada
Canada, Quebec
Hopital Sainte Justine
Montreal, Quebec, Canada
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
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

Publications of Results:
Responsible Party: Children's Oncology Group Identifier: NCT00070473     History of Changes
Other Study ID Numbers: ADVL0311
NCI-04-C-0261 ( Other Identifier: NCI Trial Identifier )
CDR0000334572 ( Other Identifier: Clinical )
COG-ADVL0311 ( Other Identifier: Children's Oncology Group )
First Posted: October 7, 2003    Key Record Dates
Last Update Posted: February 20, 2014
Last Verified: February 2014

Keywords provided by Children's Oncology Group:
unspecified childhood solid tumor, protocol specific

Additional relevant MeSH terms:
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors