Pemetrexed Disodium in Treating Young Patients With Recurrent Solid Tumors

• ClinicalTrials.gov Identifier: NCT00070473
• Recruitment Status: Completed
• First Posted: October 7, 2003
• Last Update Posted: February 20, 2014
• Sponsor: Children's Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Children's Oncology Group

Tracking Information

• First Submitted Date: October 3, 2003
• First Posted Date: October 7, 2003
• Last Update Posted Date: February 20, 2014
• Study Start Date: October 2003
• Actual Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 19, 2014): Event Free Survival [ Time Frame: Length of study ]
• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (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: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pemetrexed Disodium in Treating Young Patients With Recurrent Solid Tumors
• Official Title: 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

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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Primary Purpose: Treatment
• Condition: Unspecified Childhood Solid Tumor, Protocol Specific
• Intervention: Drug: pemetrexed disodium
• Study Arms: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 19, 2014): 33
• Original Enrollment: Not Provided
• Actual Study Completion Date: June 2008
• Actual Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00070473
• Other Study ID Numbers: 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: Not Provided
• Current Responsible Party: Children's Oncology Group
• Original Responsible Party: Not Provided
• Current Study Sponsor: Children's Oncology Group
• Original Study Sponsor: Same as current
• Collaborators: 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

• PRS Account: Children's Oncology Group
• Verification Date: February 2014