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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00070109
Recruitment Status : Completed
First Posted : October 7, 2003
Results First Posted : January 27, 2014
Last Update Posted : September 14, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE October 3, 2003
First Posted Date  ICMJE October 7, 2003
Results First Submitted Date  ICMJE December 9, 2013
Results First Posted Date  ICMJE January 27, 2014
Last Update Posted Date September 14, 2018
Study Start Date  ICMJE January 2008
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 13, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trabectedin in Treating Young Patients With Recurrent or Refractory Soft Tissue Sarcoma or Ewing's Family of Tumors
Official Title  ICMJE A Phase II Study Of Trabectedin (ET-743, Yondelis®) in Children With Recurrent Rhabdomyosarcoma, Ewing Sarcoma, or Nonrhabdomyosarcomatous Soft Tissue Sarcomas
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Previously Treated Childhood Rhabdomyosarcoma
  • Recurrent Childhood Rhabdomyosarcoma
  • Recurrent Childhood Soft Tissue Sarcoma
  • Recurrent Ewing Sarcoma
  • Peripheral Primitive Neuroectodermal Tumor
Intervention  ICMJE
  • Drug: trabectedin
    Given IV
    Other Names:
    • Ecteinascidin
    • ET 743
    • Yondelis
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: trabectedin
    • Other: pharmacological study
  • 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.
    Interventions:
    • Drug: trabectedin
    • Other: pharmacological study
  • 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.
    Interventions:
    • Drug: trabectedin
    • Other: pharmacological study
  • 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.
    Interventions:
    • Drug: trabectedin
    • Other: pharmacological study
  • 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.
    Interventions:
    • Drug: trabectedin
    • Other: pharmacological study
Publications * Baruchel S, Pappo A, Krailo M, Baker KS, Wu B, Villaluna D, Lee-Scott M, Adamson PC, Blaney SM. A phase 2 trial of trabectedin in children with recurrent rhabdomyosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft tissue sarcomas: a report from the Children's Oncology Group. Eur J Cancer. 2012 Mar;48(4):579-85. doi: 10.1016/j.ejca.2011.09.027. Epub 2011 Nov 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 10, 2013)
50
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Months to 50 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00070109
Other Study ID Numbers  ICMJE ADVL0221
NCI-2009-00357 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000329999 ( Other Identifier: Clinical Trials.gov )
COG-ADVL0221 ( Other Identifier: Children's Oncology Group )
U10CA098543 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Sylvain Baruchel, MD Children's Oncology Group
PRS Account Children's Oncology Group
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP