RATIONALE: Drugs used in chemotherapy such as ecteinascidin 743 use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of ecteinascidin 743 in treating young patients who have recurrent or refractory soft tissue sarcoma or Ewing's family of tumors.

Condition	Treatment or Intervention	Phase
recurrent childhood rhabdomyosarcoma previously treated childhood rhabdomyosarcoma recurrent childhood soft tissue sarcoma recurrent tumors of the Ewing's family	Drug: ecteinascidin 743  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• 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.
• Determine the toxicity of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.

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.

Patients are followed at 30 days.

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

Ages Eligible for Study:  up to  21 Years,  Genders Eligible for Study:  Both

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

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/mm^3
• Platelet count at least 100,000/mm^3 (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 normal for age
• Albumin at least 2.5 g/dL

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

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)

Study chairs or principal investigators

Sylvain Baruchel, MD,  Study Chair,  The Hospital for Sick Children   

Study ID Numbers:  CDR0000329999; COG-ADVL0221; NCT00070109
Record last reviewed:  September 2003
Last Updated:  December 6, 2004
Record first received:  October 3, 2003
ClinicalTrials.gov Identifier:  NCT00070109
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08