Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Sarcoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Rhabdomyosarcoma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Rhabdomyosarcoma, Embryonal

Disease Attributes

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Myosarcoma

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Soft Tissue Sarcoma

Ewing Sarcoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Trabectedin

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

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.

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.

trabectedin

pharmacological study

Sylvain Baruchel, MD

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

National Cancer Institute (NCI)

Children's Oncology Group

1 patient in Group 4 was not included in the AE analysis as the patient never received treatment.

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.

trabectedin: Given IV

pharmacological study: Correlative studies

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.

trabectedin: Given IV

Trabectedin 1.5 mg/m2 to Assess Feasibility in All Patients

Trabectedin at 1.5 mg/m2 to Assess Efficacy in Ewing Sarcoma

Trabectedin at 1.5 mg/m2 - Assess Efficacy in Rhabdomyosarcoma

Trabectedin 1.5 mg/m2 - Assess Efficacy in Nonrhabdomyosarcoma

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Canada

Region of Enrollment

Results Reporting Coordinator

Trabectedin 1.5 mg/m2- Feasibility in All Patients(Group 2)

Trabectedin 1.5 mg/m2- Efficacy in Ewing Sarcoma (Group 3)

Trabectedin 1.5 mg/m2- Efficacy in Rhabdomyosarcoma (Group 4)

Trabectedin 1.5 mg/m2-efficacy in Nonrhabdomyosarcoma(Group 5)

No pts in Group 1 were evaluated for response. 1 pt in Group 3 is excluded because the pt was removed from protocol therapy after cycle 3 when a cardiac evaluation was missed. The pt was removed prior to disease assessment on protocol therapy. 1 pt enrolled in Group 4 was excluded because patient was removed from therapy prior to chemotherapy.

Response (Complete Response [CR] and Partial Response [PR])

Trabectedin 1.3 mg/m2- Feasibility in All Patients (Group 1)

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.

trabectedin: Given IV

Trabectedin 1.5 mg/m2- Feasibility in All Patients (Group 2)

Two pts in Group 1 and 1 pt in Group 2 were excluded because they were removed from therapy prior to the DLT evaluation period and no DLT had been observed. No patients in Groups 3, 4, or 5 were evaluated for DLT.

Number of Patients With Dose-Limiting Toxicity (DLT)

Trabectedin at 1.5 mg/m2- Efficacy in Ewing Sarcoma (Group 3)

Patients for whom specimens were submitted to the pharmacokinetics laboratory with sufficient samples to calculate maximum plasma concentration of trabectedin. Group 1 and group 2 patients were excluded due to not submitting specimens.

Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Maximum Plasma Concentration (Cmax) of Trabectedin

Patients for whom specimens were submitted to the pharmacokinetics laboratory with sufficient samples to calculate apparent volume at steady state of trabectedin of trabectedin. Group 1 and group 2 patients were excluded due to not submitting specimens.

Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Apparent Volume at Steady State (Vss) of Trabectedin

Patients for whom specimens were submitted to the pharmacokinetics laboratory with sufficient samples to calculate trabectedin half life. Group 1 and group 2 patients were excluded due to not submitting specimens.

Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Half-life of Trabectedin

Patients for whom specimens were submitted to the pharmacokinetics laboratory with sufficient samples to calculate trabectedin AUC. Group 1 and group 2 patients were excluded due to not submitting specimens.

Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Area Under the Curve (AUC) of Trabectedin

Patients for whom specimens were submitted to the pharmacokinetics laboratory with sufficient samples to calculate trabectedin clearance. Group 1 and group 2 patients were excluded due to not submitting specimens.

Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Clearance of Trabectedin

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.

trabectedin: Given IV

pharmacological study: Correlative studies

Spots Global Cancer Trial Database for Trabectedin in Treating Young Patients With Recurrent or Refractory Soft Tissue Sarcoma or Ewing's Family of Tumors

Trial Identification

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Interventions

Study Description

Keywords

Eligibility

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Contact Details

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