Trabectedin in Treating Young Patients With Recurrent or Refractory Soft Tissue Sarcoma or Ewing's Family of Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00070109
First received: October 3, 2003
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

This phase II trial is studying how well trabectedin works in treating young patients with recurrent or refractory soft tissue sarcoma or Ewing's family of tumors. Drugs used in chemotherapy such as trabectedin use different ways to stop tumor cells from dividing so they stop growing or die.


Condition Intervention Phase
Previously Treated Childhood Rhabdomyosarcoma
Recurrent Childhood Rhabdomyosarcoma
Recurrent Childhood Soft Tissue Sarcoma
Recurrent Ewing Sarcoma
Peripheral Primitive Neuroectodermal Tumor
Drug: trabectedin
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of Trabectedin (ET-743, Yondelis®) in Children With Recurrent Rhabdomyosarcoma, Ewing Sarcoma, or Nonrhabdomyosarcomatous Soft Tissue Sarcomas

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response (Complete Response [CR] and Partial Response [PR]) [ Time Frame: Twenty-six (26) cycles of chemotherapy or termination of protocol therapy, whichever occurs first. ] [ Designated as safety issue: No ]
    Any patient who is enrolled and receives at least one dose of trabectedin will be considered evaluable for response if the individual receives at least one dose of trabectedin and: (1) is removed from protocol therapy because of progressive disease where progressive disease is documented either by imaging studies or clinical progression; or (2) has at least one radiographic evaluation of disease status after the start of protocol therapy and is not electively removed from protocol therapy with stable disease or is not lost to follow-up with stable disease. Patients who achieve a complete or partial response according to the RECIST criteria will be considered responders for the study design. All other patients who are evaluable for response will be considered non-responders for the study.

  • Dose-Limiting Toxicity [ Time Frame: 1 Cycle ] [ Designated as safety issue: Yes ]
    Any Grade 3 or Grade 4 non-hematologic toxicity attributable to the Investigational drug with the specific exclusion of: Grade 3 nausea and vomiting; Grade 3 transaminase (AST/ALT) elevation that return to less than or equal to Grade 1 or baseline prior to the time for the next treatment cycle; Grade 3 fever or infection; Alopecia; Grade 4 neutropenia of > 7 days duration or Grade 4 thrombocytopenia of > 7 days duration, which requires transfusion therapy on greater than 2 occasions in 7 days, or which causes a delay of more than 14 days beyond the planned interval between treatment cycles.


Secondary Outcome Measures:
  • Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method [ Time Frame: At baseline, at 1, 8, 23, 24, 26, 30, 96, and 168 hours after trabectedin infusion in course 1 ] [ Designated as safety issue: No ]
    The plasma concentration-versus-time data of trabectedin will be analyzed using noncompartmental methods. The typical population values of basic pharmacokinetic parameters will be estimated together with the interindividual variability.


Enrollment: 50
Study Start Date: January 2008
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trabectedin 1.3 mg/m2 to assess feasibility
Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Drug: trabectedin
Given IV
Other Names:
  • Ecteinascidin
  • ET 743
  • Yondelis
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Experimental: Trabectedin 1.5 mg/m2 to assess feasibility
Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Drug: trabectedin
Given IV
Other Names:
  • Ecteinascidin
  • ET 743
  • Yondelis
Experimental: Trabectedin at 1.5 mg/m2 to assess efficacy in Ewing sarcoma
Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Drug: trabectedin
Given IV
Other Names:
  • Ecteinascidin
  • ET 743
  • Yondelis
Experimental: Trabectedin to assess efficacy in rhabdomyosarcoma
Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Drug: trabectedin
Given IV
Other Names:
  • Ecteinascidin
  • ET 743
  • Yondelis
Experimental: Trabectedin to assess efficacy in nonrhabdomyosarcoma
Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Drug: trabectedin
Given IV
Other Names:
  • Ecteinascidin
  • ET 743
  • Yondelis

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the response rate in pediatric patients with recurrent or refractory soft tissue sarcomas or Ewing's sarcoma family of tumors treated with ecteinascidin 743 (trabectedin).

II. Determine the toxicity of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients.

OUTLINE:

Patients receive trabectedin IV over 3 hours on day 1. Treatment repeats every 21days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 5 years.

  Eligibility

Ages Eligible for Study:   12 Months to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be greater than or equal to 12 months of age at the time of study entry and no more than 21 years of age when initially diagnosed with the malignancy to be treated on this protocol
  • Histologically confirmed recurrent or refractory sarcoma tumors, including the following:

    • Rhabdomyosarcoma
    • Nonrhabdomyosarcomatous soft tissue sarcoma
    • Ewing's sarcoma
  • Measurable disease by imaging studies

    • Lesions assessable only by radionuclide scans are not considered measurable
    • If the only measurable lesion has been previously irradiated, then that lesion must have shown evidence of an interim increase in size
  • No significant amount of metastatic liver disease, defined as the following:

    • Lesions occupying more than 25% of the liver by imaging and abnormal liver function tests or abnormal synthetic liver function
  • Performance status - Lansky 50-100% (10 years of age and under)
  • Performance status - Karnofsky 50-100% (over 10 years of age)
  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3 (transfusion independent)
  • Hemoglobin at least 8.0 g/dL (transfusion allowed)
  • No concurrent CYP3A4 inhibitors, including the following:

    • Grapefruit juice
    • Erythromycin
    • Azithromycin
    • Clarithromycin
    • Rifampin and its analogs
    • Fluconazole
    • Ketoconazole
    • Itraconazole
    • Cimetidine
    • Cannabinoids (marijuana or dronabinol)
    • Leukotriene inhibitors used in asthma (e.g., zafirlukast, montelukast, or zileuton)
  • Bilirubin no greater than upper limit of normal (ULN)
  • Total alkaline phosphatase no greater than ULN
  • Hepatic fraction alkaline phosphatase and 5 nucleotidase no greater than ULN
  • SGOT and SGPT ≤ 2.5 times ULN
  • Albumin ≥ 2.5 g/dL
  • Gamma-glutamyl transferase < 2.5 times ULN
  • Maximum creatinine based on age as follows:

    • 0.8 mg/dL (5 years of age and under)
    • 1.0 mg/dL (6 to 10 years of age)
    • 1.2 mg/dL (11 to 15 years of age)
    • 1.5 mg/dL (over 15 years of age)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) at least 70 mL/min
  • No uncompensated congestive heart failure within the past 6 months
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 2 months after study participation
  • No active uncontrolled infection
  • Weight ≥ 15 kilograms
  • More than 1 week since prior growth factors that support platelet or white blood cell number or function
  • At least 7 days since prior biologic agents and recovered
  • No prior allogeneic stem cell transplantation
  • No other concurrent immunomodulating agents
  • More than 3 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
  • No more than 2 prior multi-agent chemotherapy regimens
  • No other concurrent anticancer chemotherapy
  • Concurrent steroids allowed
  • At least 6 weeks since prior since prior extended radiotherapy and recovered
  • No prior total body radiotherapy
  • Concurrent radiotherapy to localized painful lesions allowed provided at least 1 measurable lesion is not irradiated*
  • At least 7 days since prior enzyme-inducing anticonvulsants (e.g., carbamazepine, phenobarbital, or phenytoin)
  • No concurrent enzyme-inducing anticonvulsants
  • No other concurrent investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070109

Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Children's Hospital Central California
Madera, California, United States, 93636-8762
United States, Illinois
Childrens Memorial Hospital
Chicago, Illinois, United States, 60614
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
New York University Langone Medical Center
New York, New York, United States, 10016
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Vermont
University of Vermont
Burlington, Vermont, United States, 05401
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Canada, Ontario
Chedoke-McMaster Hospitals
Hamilton, Ontario, Canada, L8S 4L8
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Hospital Sainte-Justine
Montreal, Quebec, Canada, H3T 1C5
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Sylvain Baruchel Children's Oncology Group
  More Information

Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00070109     History of Changes
Other Study ID Numbers: ADVL0221, NCI-2009-00357, CDR0000329999, COG-ADVL0221, U10CA098543
Study First Received: October 3, 2003
Results First Received: December 9, 2013
Last Updated: December 9, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Rhabdomyosarcoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Rhabdomyosarcoma, Embryonal
Sarcoma
Sarcoma, Ewing
Neuroectodermal Tumors, Primitive, Peripheral
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Trabectedin
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 20, 2014