Ecteinascidin 743 in Treating Children With Refractory Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00006463
First received: November 6, 2000
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: ECTEINASCIDIN 743
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of ET-743 in Pediatric Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Dose Limiting Toxicity [ Designated as safety issue: Yes ]
    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 [ Designated as safety issue: Yes ]
    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 [ Time Frame: Length of study ] [ Designated as safety issue: No ]
    To determine the pharmacokinetics of vincristine and irinotecan (and its active metabolite SN-38) when administered in combination to children with refractory cancer.

  • Determine the incidence and severity of other toxicities [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]
    To determine the incidence and severity of other toxicities of this combination.

  • Seek preliminary evidence of anti-tumor activity of irinotecan plus vincristine [ Time Frame: Length of study ] [ Designated as safety issue: No ]
    To seek preliminary evidence of anti-tumor activity of irinotecan plus vincristine against recurrent solid tumors.


Enrollment: 13
Study Start Date: October 2000
Study Completion Date: September 2005
Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00006463

  Show 47 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Sylvain Baruchel, MD The Hospital for Sick Children
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00006463     History of Changes
Other Study ID Numbers: P9972, COG-P9972, POG-P9972, CDR0000068273
Study First Received: November 6, 2000
Last Updated: February 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Oncology Group:
unspecified childhood solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms
Trabectedin
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 21, 2014