Imatinib Mesylate in Treating Patients With Relapsed or Refractory Solid Tumors of Childhood

Phase 2

Completed

• Conditions: Gastrointestinal Stromal Tumor; Recurrent Childhood Soft Tissue Sarcoma; Childhood Desmoplastic Small Round Cell Tumor; Lung Metastases; Recurrent Osteosarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Childhood Synovial Sarcoma; Recurrent Neuroblastoma
• Interventions: Drug: imatinib mesylate; Other: laboratory biomarker analysis; Other: pharmacological study

• Registration Number: NCT00030667
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have relapsed or refractory solid tumors of childhood. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

Detailed Description

OBJECTIVES:

I. Determine the response rate of patients with relapsed or refractory pediatric solid tumors treated with imatinib mesylate.

II. Determine the toxicity of this drug in these patients. III. Determine the time to progression in patients treated with this drug. IV. Determine the pharmacokinetics of this drug in these patients. V. Correlate response with c-kit and platelet-derived growth factor receptor expression in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (Ewing's sarcoma/primitive neuroectodermal tumor vs osteosarcoma vs neuroblastoma vs other).

Patients receive oral imatinib mesylate once or twice daily on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Study Timeline

• Study First Submitted: 2002-02-14
• Study Start: 2002-05
• Study First Submitted QC: 2003-05-06
• Study First Posted: 2003-05-07
• Primary Completion: 2005-12
• Study Completion: 2005-12
• Status Verified: 2013-12
• Last Update Submitted: 2015-04-14
• Last Update Posted: 2015-04-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Histologically confirmed solid tumors including the following:

  • Ewing's sarcoma
  • Bone or soft tissue primitive neuroectodermal tumor
  • Osteosarcoma
  • Neuroblastoma
  • Desmoplastic small round cell tumor
  • Synovial cell sarcoma
  • Gastrointestinal stromal tumor (GIST)

• Metastatic pulmonary disease eligible

  • No pleural effusion of any size or definite radiologic evidence of pleural-based disease

• Recurrent or refractory to conventional therapy

  • GIST eligible at initial presentation

• Tumor tissue blocks must be available

• At least 1 measurable lesion

  • At least 20 mm by conventional techniques
  • At least 10 mm by spiral CT scan
  • Lesions assessable only by radionuclide scan are not considered measurable

• Performance status - Lansky 50-100% (≤ 10 years of age)

• Performance status - Karnofsky 50-100% (> 10 years of age)

• At least 2 months

• Absolute neutrophil count ≥ 1,000/mm^3*

• Platelet count ≥ 75,000/mm^3* (transfusion independent)

• Hemoglobin ≥ 8.0 g/dL* (RBC transfusions allowed)

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• ALT ≤ 2.5 times ULN

• INR < 1.5

• PTT ≤ ULN

• Fibrinogen ≥ lower limit of normal

• Creatinine normal for age

• Glomerular filtration rate ≥ 70 mL/min

• No uncontrolled infection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception

• At least 1 week since prior biologic therapy or immunotherapy and recovered

• At least 1 week since prior growth factors

• No concurrent immunomodulating agents

• At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered

• No concurrent chemotherapy

• No concurrent steroids

• Recovered from prior radiotherapy

• At least 2 weeks since prior local palliative radiotherapy (small port)

• At least 3 months since prior craniospinal radiotherapy or radiotherapy to 50% or more of pelvis

• At least 6 weeks since other prior substantial bone marrow radiation

• No concurrent radiotherapy during first course of treatment

• Concurrent palliative radiotherapy to local painful lesions allowed after first course of treatment provided there is no evidence of disease progression and at least 1 measurable lesion remains outside radiation port

• No concurrent therapeutic doses of warfarin

• No concurrent anticonvulsants that induce the cytochrome p450 enzyme system (e.g., phenytoin, carbamazepine, and phenobarbital)

• Concurrent benzodiazepines and gabapentin allowed

• Concurrent low-molecular weight heparin allowed

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (imatinib mesylate)	imatinib mesylate	Patients receive oral imatinib mesylate once or twice daily on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Treatment (imatinib mesylate)	laboratory biomarker analysis	Patients receive oral imatinib mesylate once or twice daily on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Treatment (imatinib mesylate)	pharmacological study	Patients receive oral imatinib mesylate once or twice daily on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Toxicity reported using the CTC version 2.0	Up to 2 years
Response rate, determined using the RECIST criteria	Up to 2 years	95% confidence interval will be computed.

Secondary Outcome Measures

Name	Time	Method
Time to disease progression	Up to 2 years	Calculated by the method of Kaplan and Meier.

Trial Locations

Locations (1)

Children's Oncology Group; 🇺🇸 Arcadia, California, United States