Ecteinascidin 743 in Treating Children With Refractory Solid Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Childhood Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: ECTEINASCIDIN 743

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6001
      • Princess Margaret Hospital for Children
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3H 1P3
      • Montreal Children's Hospital
    • Montreal, Quebec, Canada, H3T 1C5
      • Hopital Sainte Justine
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego Cancer Center
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center, UCLA
    • Los Angeles, California, United States, 91010
      • Beckman Research Institute, City of Hope
    • Los Angeles, California, United States, 90027-0700
      • Children's Hospital Los Angeles
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital at Stanford
    • San Francisco, California, United States, 94115-0128
      • UCSF Cancer Center and Cancer Research Institute
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2970
      • Children's National Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610-100277
      • Shands Hospital and Clinics, University of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital - Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital, Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5265
      • Indiana University Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Oncology Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02111
      • Boston Floating Hospital Infants and Children
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Mott Children's Hospital
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
    • Saint Louis, Missouri, United States, 63104
      • Cardinal Glennon Children's Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10032
      • Columbia Presbyterian Hospital
    • Syracuse, New York, United States, 13210
      • State University of New York - Upstate Medical University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Children's Hospital Medical Center - Cincinnati
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29425-0721
      • Medical University of South Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38105-2794
      • Saint Jude Children's Research Hospital
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt Cancer Center
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center - Fort Worth
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030-4009
      • University of Texas - MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78284-7811
      • University of Texas Health Science Center at San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Huntsman Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98105
      • Children's Hospital and Regional Medical Center - Seattle
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-0001
      • University of Wisconsin Hospital and Clinics
    • Milwaukee, Wisconsin, United States, 53226
      • Midwest Children's Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Therapy ECTEINASCIDIN 743 (1100 ug/m2 )	Drug: ECTEINASCIDIN 743; Other Names: ET-743; NSC S648766; IND 50,286
Experimental: ECTEINASCIDIN 743 (1300 ug/m2)	Drug: ECTEINASCIDIN 743; Other Names: ET-743; NSC S648766; IND 50,286

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival	Length of study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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
Determine the incidence and severity of other toxicities	To determine the incidence and severity of other toxicities of this combination.	Length of study
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

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Sylvain Baruchel, MD, The Hospital for Sick Children

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Primary Completion (Actual): January 1, 2005
• Study Completion (Actual): September 1, 2005

Study Registration Dates

• First Submitted: November 6, 2000
• First Submitted That Met QC Criteria: April 23, 2004
• First Posted (Estimate): April 26, 2004

Study Record Updates

• Last Update Posted (Estimate): February 21, 2014
• Last Update Submitted That Met QC Criteria: February 19, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: unspecified childhood solid tumor, protocol specific
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Trabectedin
• Other Study ID Numbers: P9972; COG-P9972 (Other Identifier: Children's Oncology Group); POG-P9972 (Other Identifier: Pediatric Oncology Group); CDR0000068273 (Other Identifier: Clinical Trials.gov)