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

Inclusion Criteria:

- 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