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

August 13, 2018 updated by: Children's Oncology Group

A Phase II Study Of Trabectedin (ET-743, Yondelis®) in Children With Recurrent Rhabdomyosarcoma, Ewing Sarcoma, or Nonrhabdomyosarcomatous Soft Tissue Sarcomas

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Trabectedin 1.3 mg/m2 to assess feasibility in all patients
Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21 days for up to 26 courses in the absence of disease progression or unacceptable toxicity. A cohort of 6 patients will be enrolled at the 1.3 mg/m2 dose level.
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: trabectedin
Given IV
Other Names:
  • Yondelis
  • Ecteinascidin
  • ET 743
Experimental: Trabectedin 1.5 mg/m2 to assess feasibility in all patients
Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21 days for up to 26 courses in the absence of disease progression or unacceptable toxicity. Six toxicity-evaluable patients are assigned this treatment.
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: trabectedin
Given IV
Other Names:
  • Yondelis
  • Ecteinascidin
  • ET 743
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 21 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: trabectedin
Given IV
Other Names:
  • Yondelis
  • Ecteinascidin
  • ET 743
Experimental: Trabectedin at 1.5 mg/m2 - assess efficacy in rhabdomyosarcoma
Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: trabectedin
Given IV
Other Names:
  • Yondelis
  • Ecteinascidin
  • ET 743
Experimental: Trabectedin 1.5 mg/m2 - assess efficacy in nonrhabdomyosarcoma
Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Drug: trabectedin
Given IV
Other Names:
  • Yondelis
  • Ecteinascidin
  • ET 743

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Response (Complete Response [CR] and Partial Response [PR])
Time Frame: Twenty-six (26) cycles of chemotherapy or termination of protocol therapy, whichever occurs first.
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 response (CR) - disappearance of all target lesions or partial response (PR) - >=30% decrease in the sum of the longest diameter of target lesions 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.
Twenty-six (26) cycles of chemotherapy or termination of protocol therapy, whichever occurs first.
Number of Patients With Dose-Limiting Toxicity (DLT)
Time Frame: 1 Cycle
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.
1 Cycle
Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Maximum Plasma Concentration (Cmax) of Trabectedin
Time Frame: From baseline up to168 hours after trabectedin infusion in course 1
The plasma concentrations at each time point were determined by miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method. The plasma concentration-versus-time data of trabectedin were estimated using non-compartmental methods. Individual time points were not available, so one estimated Cmax was derived for each patient.
From baseline up to168 hours after trabectedin infusion in course 1
Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Apparent Volume at Steady State (Vss) of Trabectedin
Time Frame: From baseline up to168 hours after trabectedin infusion in course 1
The plasma concentrations at each time point were determined by miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method. The plasma concentration-versus-time data of trabectedin were estimated using non-compartmental methods. Individual time points were not available, so one estimated Vss was derived for each patient.
From baseline up to168 hours after trabectedin infusion in course 1
Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Half-life of Trabectedin
Time Frame: From baseline up to168 hours after trabectedin infusion in course 1
The plasma concentrations at each time point were determined by miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method. The plasma concentration-versus-time data of trabectedin were estimated using non-compartmental methods. Individual time points were not available, so one estimated Half-life was derived for each patient.
From baseline up to168 hours after trabectedin infusion in course 1
Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Area Under the Curve (AUC) of Trabectedin
Time Frame: From baseline up to168 hours after trabectedin infusion in course 1
The plasma concentrations at each time point were determined by miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method. The plasma concentration-versus-time data of trabectedin were estimated using non-compartmental methods. Individual time points were not available, so one estimated AUC was derived for each patient.
From baseline up to168 hours after trabectedin infusion in course 1
Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Clearance of Trabectedin
Time Frame: From baseline up to168 hours after trabectedin infusion in course 1
The plasma concentrations at each time point were determined by miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method. The plasma concentration-versus-time data of trabectedin were estimated using non-compartmental methods. Individual time points were not available, so one estimated Clearance was derived for each patient.
From baseline up to168 hours after trabectedin infusion in course 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Oncology Group

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sylvain Baruchel, MD, Children's Oncology Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 3, 2003

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 6, 2003

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 7, 2003

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 14, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ADVL0221
  • U10CA098543 (U.S. NIH Grant/Contract)
  • NCI-2009-00357 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • CDR0000329999 (Other Identifier: Clinical Trials.gov)
  • COG-ADVL0221 (Other Identifier: Children's Oncology Group)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings