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Pemetrexed Disodium in Treating Young Patients With Recurrent Solid Tumors

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ClinicalTrials.gov 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

Tracking Information
First Submitted Date  ICMJE October 3, 2003
First Posted Date  ICMJE October 7, 2003
Last Update Posted Date February 20, 2014
Study Start Date  ICMJE October 2003
Actual Primary Completion Date March 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 19, 2014)
Event Free Survival [ Time Frame: Length of study ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2014)
  • 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.
  • Maximum Tolerated Dose [ Time Frame: Length of study ]
    The MTD will be that dose at which fewer than one-third of patients experience DLT
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Pemetrexed Disodium in Treating Young Patients With Recurrent Solid Tumors
Official Title  ICMJE A Phase I Study of Pemetrexed (LY231514, Alimta) in Children and Adolescents With Recurrent Solid Tumors
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE Unspecified Childhood Solid Tumor, Protocol Specific
Intervention  ICMJE Drug: pemetrexed disodium
Study Arms  ICMJE Not Provided
Publications * Malempati S, Nicholson HS, Reid JM, Blaney SM, Ingle AM, Krailo M, Stork LC, Melemed AS, McGovern R, Safgren S, Ames MM, Adamson PC; Children's Oncology Group. Phase I trial and pharmacokinetic study of pemetrexed in children with refractory solid tumors: the Children's Oncology Group. J Clin Oncol. 2007 Apr 20;25(12):1505-11. doi: 10.1200/JCO.2006.09.1694. Erratum In: J Clin Oncol. 2008 Jan 1;26(1):165.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 19, 2014)
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 2008
Actual Primary Completion Date March 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE


  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00070473
Other Study ID Numbers  ICMJE ADVL0311
NCI-04-C-0261 ( Other Identifier: NCI Trial Identifier )
CDR0000334572 ( Other Identifier: Clinical Trials.gov )
COG-ADVL0311 ( Other Identifier: Children's Oncology Group )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Children's Oncology Group
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE Children's Oncology Group
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
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
PRS Account Children's Oncology Group
Verification Date February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP