Clinical trial NCT00008424: Irinotecan in Treating Children With Refractory or Advanced Solid Tumors Who Are Receiving Anticonvulsants
Official title: A Phase I Study of Irinotecan in Patients With Refractory Solid Tumors Who Are Concomitantly Receiving Anticonvulsants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Childhood Solid Tumor, Protocol Specific
Keywords: unspecified childhood solid tumor, protocol specific
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-06-05
Enrollment: 7
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

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