Clinical trial NCT00006463: Ecteinascidin 743 in Treating Children With Refractory Solid Tumors
Official title: Phase I Study of ET-743 in Pediatric Refractory Solid Tumors
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: 2004-04-26
Enrollment: 13
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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. Ecteinascidin 743 may be an effective treatment for solid tumors.

PURPOSE: Phase I trial to study the effectiveness of ecteinascidin 743 in treating children who have refractory solid tumors.

Detailed description: OBJECTIVES: I. Determine the maximum tolerated dose and dose-limiting toxicity of ecteinascidin 743 in pediatric patients with refractory solid tumors. II. Determine the pharmacokinetics of this drug in these patients. III. Determine the antitumor activity of this drug in this patient population.

OUTLINE: This is a dose escalation, multicenter study. Patients are stratified according to pretreatment (pretreated vs less heavily pretreated). Patients receive ecteinascidin 743 IV over 3 hours on day 1. Treatment continues every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ecteinascidin 743 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 toxicities.

PROJECTED ACCRUAL: A total of 3-20 patients will be accrued for this study within 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically confirmed malignant solid tumor at original diagnosis Refractory to standard treatment or no curative therapy available No CNS tumor No bone marrow metastases (for less heavily pretreated stratum only)

PATIENT CHARACTERISTICS: Age: At least 365 days to 17 years Performance status: Karnofsky 50-100% (for patients older than 10 years) Lansky 50-100% (for patients 10 years and younger) Life expectancy: At least 8 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 (transfusion independent) Hemoglobin at least 8.0 g/dL (RBC transfusion allowed) Hepatic: Bilirubin no greater than normal SGPT no greater than 2.5 times normal Albumin at least 2 g/dL Alkaline phosphatase normal Gamma glutamyl transferase less than 2.5 times normal Renal: Creatinine no greater than 1.5 times normal OR Creatinine clearance or GFR at least lower limit of normal Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Creatine phosphokinase less than 2 times normal No uncontrolled infection Seizure disorder allowed if well controlled on anticonvulsants No CNS toxicity greater than grade II

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 week since prior biologic therapy and recovered At least 1 week since prior growth factor therapy At least 6 months since prior peripheral blood stem cell transplantation and no evidence of graft-vs-host disease For less heavily pretreated stratum: No prior peripheral blood stem cell transplantation Chemotherapy: At least 4 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered No prior ecteinascidin 743 For less heavily pretreated stratum: No more than 2 prior chemotherapy regimens Endocrine therapy: Not specified Radiotherapy: At least 2 weeks since prior local palliative radiotherapy (small port) At least 6 weeks since prior substantial bone marrow radiotherapy At least 6 months since prior craniospinal radiotherapy or radiotherapy to 50% or greater of pelvis For less heavily pretreated stratum: No prior craniospinal irradiation of 18Gy or greater No prior irradiation to greater than 50% of pelvis Recovered from toxic effects of prior radiotherapy Surgery: Not specified Other: No concurrent foods or medication that interferes with P-450 metabolism Anticonvulsants allowed

Primary outcomes:
measure: Progression Free Survival
timeFrame: Length of study
Secondary outcomes:
measure: Dose Limiting Toxicity
measure: Determine a safe and tolerable dose of vincristine, when administered with irinotecan
measure: Determine the pharmacokinetics of vincristine and irinotecan
timeFrame: Length of study
measure: Determine the incidence and severity of other toxicities
timeFrame: Length of study
measure: Seek preliminary evidence of anti-tumor activity of irinotecan plus vincristine
timeFrame: Length of study
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
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: Los Angeles
country: United States
facility: Beckman Research Institute, City of Hope
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: 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: Johns Hopkins Oncology Center
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 Cancer Center
state: Tennessee
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: 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: 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: Montreal Children's Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
Study officials:
affiliation: The Hospital for Sick Children
name: Sylvain Baruchel, MD
role: STUDY_CHAIR
References:
citation: Lau L, Supko JG, Blaney S, Hershon L, Seibel N, Krailo M, Qu W, Malkin D, Jimeno J, Bernstein M, Baruchel S. A phase I and pharmacokinetic study of ecteinascidin-743 (Yondelis) in children with refractory solid tumors. A Children's Oncology Group study. Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):672-7.