Chemotherapy in Treating Children With Recurrent or Refractory Sarcomas

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Sarcoma

Treatments: Drug: topotecan hydrochloride

Study type: Interventional

Funder types: NIH

Identifiers

NCT00003745

CDR0000066864 (Registry Identifier)

CCG-09713

NCI-2012-01841

CCG-A09713

COG-A09713

Details and patient eligibility

About

Phase II trial to study the effectiveness of topotecan in treating children who have recurrent, relapsed, or refractory sarcoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

Full description

OBJECTIVES:

I. Determine the response rate in children with recurrent or refractory brain tumors, sarcomas, or neuroblastomas treated with topotecan. (Brain tumor and neuroblastoma strata closed to accrual effective 07/02/2001) II. Assess the toxicity of this regimen in a larger group of patients treated at the currently defined maximum tolerated dose.

OUTLINE: This is a multicenter study.

Patients receive topotecan IV continuously on days 1-21. Treatment continues at least every 4 weeks in the absence of unacceptable toxicity or disease progression.

Patients are followed every 3 months.

Enrollment: 125 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy that is relapsed or refractory to conventional therapy at original diagnosis including:

  • Brain tumors

    • Gliomas or astrocytomas
    • Medulloblastomas or primitive neuroectodermal tumor (PNET) in CNS
    • (Brain tumor stratum closed to accrual effective 07/02/2001)

  • Sarcomas

    • Soft tissue sarcoma (undifferentiated sarcoma, embryonal or alveolar rhabdomyosarcoma (RMS), or non-RMS soft tissue sarcoma)
    • Osteosarcoma
    • Ewing's sarcoma/peripheral PNET tumors

  • Neuroblastoma

    • (Neuroblastoma stratum closed to accrual effective 07/02/2001)

• Histology requirement waived for brain stem tumors (Brain tumor stratum closed to accrual effective 07/02/2001)

• Measurable disease documented by clinical, radiographic, or histologic criteria

• Lesions in previously irradiated fields may be used to assess tumor response if there has been evidence of subsequent tumor growth in those fields

• No bone marrow metastases with granulocytopenia and/or thrombocytopenia

PATIENT CHARACTERISTICS:

Age:

• 30 days to 21 years at diagnosis

Performance status:

• ECOG 0-2

Life expectancy:

• More than 2 months

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm3
• Hemoglobin at least 10.0 g/dL (may receive RBC transfusions)
• Platelet count at least 100,000/mm3 (50,000/mm3 if post bone marrow transplantation) (transfusion independent)

Hepatic:

• Bilirubin no greater than 1.5 times normal
• SGOT or SGPT less than 2.5 times normal

Renal:

• Creatinine no greater than 1.5 times normal OR
• Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Neurologic:

• No greater than grade 2 CNS toxicity OR
• Stable CNS status for brain tumors (Brain tumor stratum closed to accrual effective 07/02/2001)
• Seizure disorders allowed if well-controlled with anticonvulsants

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 3 months since prior bone marrow transplantation and recovered
• At least 2 weeks since prior cytokines and recovered
• No concurrent filgrastim (G-CSF) or other cytokines
• No concurrent immunomodulating agents

Chemotherapy:

• At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered
• No prior topotecan or other camptothecins
• No other concurrent anticancer chemotherapy

Endocrine therapy:

• Concurrent corticosteroids for CNS tumors with increased intracranial pressure allowed (Brain tumor stratum closed to accrual effective 07/02/2001)

Radiotherapy:

• At least 2 months since prior craniospinal radiotherapy or radiotherapy to more than 50% of the bone marrow and recovered
• Concurrent radiotherapy to localized painful lesions allowed provided that at least 1 measurable lesion is not irradiated

Other:

• Recovered from any other prior therapy

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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125 participants in 1 patient group

Arm I

Experimental group

Description:

Patients receive topotecan IV continuously on days 1-21. Treatment continues at least every 4 weeks in the absence of unacceptable toxicity or disease progression.

Treatment:

Drug: topotecan hydrochloride