Ecteinascidin 743 in Treating Children With Refractory Solid Tumors

Unspecified Childhood Solid Tumor, Protocol Specific Clinical Trial

Official title:

Phase I Study of ET-743 in Pediatric Refractory Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006463
• Other study ID #: P9972
• Secondary ID: COG-P9972POG-P99
• Status: Completed
• Phase: Phase 1
• First received: November 6, 2000
• Last updated: February 19, 2014
• Start date: October 2000
• Est. completion date: September 2005

Study information

• Verified date: February 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: September 2005
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 17 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Drug:
• ECTEINASCIDIN 743

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	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	Johns Hopkins Oncology Center	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	Children's Hospital of Michigan	Detroit	Michigan
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	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	Beckman Research Institute, City of Hope	Los Angeles	California
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 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, 

References & Publications (1)

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. C — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival		Length of study	Yes
Secondary	Dose Limiting Toxicity	To determine the maximum tolerated dose (MTD) of vincristine, when used in combination with irinotecan, and the dose-limiting toxicity (DLT) of this combination; irinotecan will be administered IV over 1 hour x 5 days, q 21 days, with vincristine IVP days 1, 8, 15, 22, 29, every 42 days, to children with refractory solid tumors.		Yes
Secondary	Determine a safe and tolerable dose of vincristine, when administered with irinotecan	To determine a safe and tolerable dose of vincristine, when administered with irinotecan, for future evaluation in phase II clinical trials.		Yes
Secondary	Determine the pharmacokinetics of vincristine and irinotecan	To determine the pharmacokinetics of vincristine and irinotecan (and its active metabolite SN-38) when administered in combination to children with refractory cancer.	Length of study	No
Secondary	Determine the incidence and severity of other toxicities	To determine the incidence and severity of other toxicities of this combination.	Length of study	Yes
Secondary	Seek preliminary evidence of anti-tumor activity of irinotecan plus vincristine	To seek preliminary evidence of anti-tumor activity of irinotecan plus vincristine against recurrent solid tumors.	Length of study	No