Pemetrexed Disodium in Treating Young Patients With Recurrent Solid Tumors

Unspecified Childhood Solid Tumor, Protocol Specific Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00070473
• Other study ID #: ADVL0311
• Secondary ID: NCI-04-C-0261CDR
• Status: Completed
• Phase: Phase 1
• First received: October 3, 2003
• Last updated: February 19, 2014
• Start date: October 2003
• Est. completion date: June 2008

Study information

• Verified date: February 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: June 2008
• Est. primary completion date: March 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Drug:
• pemetrexed disodium

Locations

Country	Name	City	State
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
United States	NCI - Pediatric Oncology Branch	Bethesda	Maryland
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Baylor University Medical Center - Houston	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Fairview University Medical Center - University Campus	Minneapolis	Minnesota
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Stanford Cancer Center at Stanford University Medical Center	Stanford	California
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Free Survival		Length of study	Yes
Secondary	Dose Limiting Toxicity	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.	Length of study	Yes
Secondary	Maximum Tolerated Dose	The MTD will be that dose at which fewer than one-third of patients experience DLT	Length of study	No