Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Ecteinascidin 743 in Treating Young Patients With Recurrent or Refractory Soft Tissue Sarcoma or Ewing's Family of Tumors

Basic Trial Information

Objectives

1. 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.
2. Determine the toxicity of this drug in these patients.
3. Determine the pharmacokinetics of this drug in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed recurrent or refractory sarcomas, 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

Prior/Concurrent Therapy:

Biologic therapy

• 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

Chemotherapy

• 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

Endocrine therapy

• Concurrent steroids allowed

Radiotherapy

• See Disease Characteristics
• 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*

 [Note: *Any irradiated lesion cannot be used to assess tumor response]

Surgery

• Not specified

Other

• 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
• 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)

Patient Characteristics:

Age

• 21 and under (at time of diagnosis)

Performance status

• Lansky 50-100% (10 years of age and under)
• Karnofsky 50-100% (over 10 years of age)

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,000/mm³
• Platelet count at least 100,000/mm³ (transfusion independent)
• Hemoglobin at least 8.0 g/dL (transfusion allowed)

Hepatic

• See Disease Characteristics
• Bilirubin no greater than upper limit of normal (ULN)
• Total alkaline phosphatase no greater than ULN

  OR

• 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

Renal

• 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)

  OR

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) at least 70 mL/min

Cardiovascular

• No uncompensated congestive heart failure within the past 6 months

Other

• 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

Expected Enrollment

A total of 30-60 patients (10-20 per stratum) will be accrued for this study within 2 years.

Outcomes

Response rate

Toxicity
Pharmacokinetics

Outline

This is a multicenter study. Patients are stratified according to disease (Ewing's sarcoma family of tumors vs rhabdomyosarcoma vs nonrhabdomyosarcomatous soft tissue sarcoma).

Patients receive ecteinascidin 743 IV over 3 hours on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection at baseline and periodically during course 1 for pharmacokinetic studies.

Patients are followed at 30 days.

Baruchel S, Pappo A, Krailo M, et al.: 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 : , 2011.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Sylvain Baruchel, MD, Protocol chair		Ph: 416-813-7795

Registry Information
Official Title		A Phase II Study Of Trabectedin (ET-743, Yondelis®) in Children With Recurrent Rhabdomyosarcoma, Ewing Sarcoma, or Nonrhabdomyosarcomatous Soft Tissue Sarcoma
Trial Start Date		2008-01-28
Trial Completion Date		2010-10-20
Registered in ClinicalTrials.gov		NCT00070109
Date Submitted to PDQ		2003-08-14
Information Last Verified		2010-11-12
NCI Grant/Contract Number		CA98543

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