Irinotecan in Treating Children With Refractory or Advanced Solid Tumors Who Are Receiving Anticonvulsants

Unspecified Childhood Solid Tumor, Protocol Specific Clinical Trial

Official title:

A Phase I Study of Irinotecan in Patients With Refractory Solid Tumors Who Are Concomitantly Receiving Anticonvulsants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00008424
• Other study ID #: P9871
• Secondary ID: COG-P9871POG-P98
• Status: Completed
• Phase: Phase 1
• First received: January 6, 2001
• Last updated: May 2, 2014
• Start date: October 2000
• Est. completion date: September 2006

Study information

• Verified date: May 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 use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of irinotecan in treating children with refractory or advanced solid tumors who are receiving anticonvulsants.

Description:

OBJECTIVES:

• Determine the maximum tolerated dose of irinotecan in children with refractory or advanced solid tumors receiving anticonvulsants.

• Determine the dose-limiting toxicity of irinotecan in this patient population.

• Evaluate the pharmacokinetic behavior of this treatment regimen in these patients.

• Determine, preliminarily, the antitumor activity of this treatment regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to type of concurrent anticonvulsant (enzyme activating anticonvulsants vs valproic acid vs other anticonvulsants).

Patients receive irinotecan IV over 1 hour daily for 5 days. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 6 months for up to 4 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 3-25 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: September 2006
• Est. primary completion date: September 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy refractory to conventional therapy or for which no conventional therapy exists

• Histologic confirmation not required for brain stem tumors

• Concurrently on anticonvulsants at a steady level for at least 2 weeks

PATIENT CHARACTERISTICS:

Age:

• 1-21 years old

Performance status:

• Karnofsky 50-100% (over 10 years of age)

• Lansky 50-100% (10 years of age or under)

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Neutrophil count at least 1,000/mm3

• Platelet count at least 100,000/mm3 (transfusion independent)

• Hemoglobin at least 8.0 g/dL (red blood cell transfusions allowed)

Hepatic:

• Bilirubin no greater than 1.5 times normal for age

• SGPT less than 5 times normal for age

• Albumin at least 2 g/dL

Renal:

• Creatinine no greater than 1.5 times normal for age OR

• Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal for age

Other:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No uncontrolled infection

• No evidence of active graft-vs-host disease

• Neurologic deficits for CNS tumors stable for at least 2 weeks prior to study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 1 week since prior antineoplastic biologic therapy

• At least 6 months since prior allogeneic stem cell transplantation

• At least 1 week since prior growth factors

• No concurrent sargramostim (GM-CSF)

• No concurrent prophylactic growth factors during first course of study therapy

• Recovered from prior immunotherapy

Chemotherapy:

• At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosourea) and recovered

Endocrine therapy:

• Concurrent dexamethasone for CNS tumors with increased intracranial pressure allowed if dose stable or decreasing for at least 2 weeks prior to study

Radiotherapy:

• At least 2 weeks since prior local palliative radiotherapy (small part)

• At least 6 months since prior craniospinal radiotherapy

• At least 6 months since prior radiotherapy to at least 50% of pelvis

• At least 6 weeks since prior substantial bone marrow radiotherapy

• Recovered from prior radiotherapy

Surgery:

• Not specified

Other:

• No other concurrent investigational agent

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Drug:
• irinotecan hydrochloride

Locations

Country	Name	City	State
Australia	Women's and Children's Hospital	North Adelaide	South Australia
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	McGill University Health Center - Montreal Children's Hospital	Montreal	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
United States	Mott Children's Hospital	Ann Arbor	Michigan
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Boston Floating Hospital Infants and Children	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Children's Memorial Hospital, Chicago	Chicago	Illinois
United States	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Children's Hospital of Denver	Denver	Colorado
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Cancer Center and Beckman Research Institute, City of Hope	Duarte	California
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	Shands Hospital and Clinics, University of Florida	Gainesville	Florida
United States	CCOP - Green Bay	Green Bay	Wisconsin
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Baylor College of Medicine	Houston	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of California San Diego Cancer Center	La Jolla	California
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Saint Jude Children's Research Hospital	Memphis	Tennessee
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Columbia Presbyterian Hospital	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Children's Hospital of Orange County	Orange	California
United States	Lucile Packard Children's Hospital at Stanford	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	State University of New York - Upstate Medical University	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,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerable dose (MTD) of irinotecan			Yes