Rebeccamycin Analogue in Treating Children With Solid Tumors or Non-Hodgkin's Lymphoma

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Sarcoma; Neuroblastoma; Brain and Central Nervous System Tumors; Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific; Retinoblastoma

Treatments: Drug: becatecarin

Study type: Interventional

Funder types: NIH

Identifiers

NCT00006102

NCI-2012-01851

CDR0000068111 (Registry Identifier)

COG-P9963

Details and patient eligibility

About

Phase II trial to study the effectiveness of rebeccamycin analogue in treating children who have solid tumors or non-Hodgkin's lymphoma. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

Full description

OBJECTIVES:

I. Determine the response in children with solid tumors or non-Hodgkin's lymphoma treated with rebeccamycin analogue.

II. Determine and maintain a plasma concentration of at least 5 µg/mL of this drug in these patients.

III. Determine the toxicity of this drug in these patients. IV. Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients with solid tumors are stratified according to tumor histology (neuroblastoma vs Ewing's sarcoma [closed to accrual as of 5/19/03]/peripheral primative neuroectodermal tumor [PNET] vs osteosarcoma [closed to accrual as of 5/19/03] vs rhabdomyosarcoma vs non-Hodgkin's lymphoma vs other solid tumors). Patients with CNS tumors are stratified according to tumor histology (medulloblastoma/PNET vs ependymoma vs brainstem glioma vs other CNS tumors).

Patients receive rebeccamycin analogue IV over 1 hour on day 1. Treatment continues every 21 days for a total of 16 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 1 year, every 2 months for 2 years, every 6 months for 1 year, and then annually thereafter.

Enrollment: 200 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumors

  • Neuroblastoma

  • Ewing's sarcoma/peripheral primitive neuroectodermal tumor (PNET)(Ewing's sarcoma closed to accrual as of 5/19/03)

  • Osteosarcoma (closed to accrual as of 5/19/03)

  • Rhabdomyosarcoma

  • Other extracranial solid tumors

  • CNS/brain tumors:

    • Medulloblastoma/PNET
    • Ependymoma
    • Brainstem glioma
    • Other CNS tumors

  • Histological verification may be waived for brainstem glioma and classic optic glioma, but biopsy recommended OR

• Histologically or cytologically proven non-Hodgkin's lymphoma

  • Refractory to standard treatment and no curative therapy available

• Measurable disease

PATIENT CHARACTERISTICS:

Age:

• 21 and under at time of original diagnosis

Performance status:

• Karnofsky 50-100% in patients over 10 years of age
• Lansky 50-100% in patients age 10 and under

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 75,000/mm^3
• Hemoglobin greater than 8.0 g/dL

Hepatic:

• Bilirubin normal for age
• SGPT less than 2.5 times upper limit of normal
• Amylase normal
• Lipase normal

Renal:

• Creatinine normal for age OR
• Glomerular filtration rate at least 60 mL/min

Other:

• No concurrent uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Recovered from prior immunotherapy

Chemotherapy:

• At least 6 weeks since prior nitrosourea and recovered
• Recovered from any other prior chemotherapy
• No more than two prior chemotherapy regimens

Endocrine therapy:

• CNS tumor patients receiving dexamethasone must be on stable or decreasing dose at least 2 weeks prior to study entry

Radiotherapy:

• At least 6 weeks since prior extended radiotherapy and recovered
• No prior total body irradiation

Surgery:

• Prior radiosurgery allowed

Other:

• No concurrent use of the following foods or medications:

  • Grapefruit juice
  • Erythromycin
  • Azithromycin
  • Clarithromycin
  • Rifampin and analogues
  • Fluconazole
  • Ketoconazole
  • Itraconazole
  • Cimetidine
  • Cannabinoids (marijuana or dronabinol)
  • Leukotriene inhibitors (e.g., zafirlukast and zileuton)

• No other concurrent anticancer or investigational agents

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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200 participants in 1 patient group

Arm I

Experimental group

Description:

Patients with solid tumors are stratified according to tumor histology (neuroblastoma vs Ewing's sarcoma \[closed to accrual as of 5/19/03\]/peripheral primative neuroectodermal tumor \[PNET\] vs osteosarcoma \[closed to accrual as of 5/19/03\] vs rhabdomyosarcoma vs non-Hodgkin's lymphoma vs other solid tumors). Patients with CNS tumors are stratified according to tumor histology (medulloblastoma/PNET vs ependymoma vs brainstem glioma vs other CNS tumors). Patients receive rebeccamycin analogue IV over 1 hour on day 1. Treatment continues every 21 days for a total of 16 courses in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: becatecarin