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Pemetrexed Disodium in Treating Young Patients With Recurrent Solid Tumors

Sponsor
Children's Oncology Group (Other)
Overall Status
Completed
CT.gov ID
NCT00070473
Collaborator
National Cancer Institute (NCI) (NIH)
33
Enrollment
20
Locations
56
Duration (Months)
1.7
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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
  • Drug: pemetrexed disodium
 Phase 1

Detailed Description

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.

Study Design

Study Type:
Interventional
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 :
Oct 1, 2003
Actual Primary Completion Date :
Mar 1, 2006
Actual Study Completion Date :
Jun 1, 2008

Outcome Measures

Primary Outcome Measures

  1. Event Free Survival [Length of study]

Secondary Outcome Measures

  1. Dose Limiting Toxicity [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 [Length of study]

    The MTD will be that dose at which fewer than one-third of patients experience DLT

Eligibility Criteria

Criteria

Ages Eligible for Study:
1 Year to 21 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Children's Hospital Los Angeles Los Angeles California United States 323669
2 Stanford Cancer Center at Stanford University Medical Center Stanford California United States 94305
3 Children's National Medical Center Washington District of Columbia United States 20010-2970
4 Indiana University Cancer Center Indianapolis Indiana United States 46202-5289
5 NCI - Pediatric Oncology Branch Bethesda Maryland United States 301496
6 Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston Massachusetts United States 02115
7 Fairview University Medical Center - University Campus Minneapolis Minnesota United States 55455
8 Mayo Clinic Cancer Center Rochester Minnesota United States 55905
9 University of Mississippi Medical Center Jackson Mississippi United States 39216-4505
10 Herbert Irving Comprehensive Cancer Center at Columbia University New York New York United States 10032
11 SUNY Upstate Medical University Hospital Syracuse New York United States 13210
12 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229-3039
13 Cancer Institute at Oregon Health and Science University Portland Oregon United States 97239-3098
14 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 215590
15 Children's Hospital of Pittsburgh Pittsburgh Pennsylvania United States 15213
16 Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas Texas United States 75390
17 Baylor University Medical Center - Houston Houston Texas United States 832822
18 Children's Hospital and Regional Medical Center - Seattle Seattle Washington United States 206987
19 Hospital for Sick Children Toronto Ontario Canada
20 Hopital Sainte Justine Montreal Quebec Canada

Sponsors and Collaborators

  • Children's Oncology Group
  • National Cancer Institute (NCI)

Investigators

  • 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00070473
Other Study ID Numbers:
  • ADVL0311
  • NCI-04-C-0261
  • CDR0000334572
  • COG-ADVL0311
First Posted:
Oct 7, 2003
Last Update Posted:
Feb 20, 2014
Last Verified:
Feb 1, 2014
Keywords provided by Children's Oncology Group
unspecified childhood solid tumor, protocol specific
Additional relevant MeSH terms:
Neoplasms
Pemetrexed

Study Results

No Results Posted as of Feb 20, 2014