Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Lobradimil and Carboplatin in Treating Children With Brain Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 21 and under at diagnosis NCI NCI-98-C-0074H CCG-09716, ALK-01-041, NCI-T98-0011, COG-C09716, T98-0011, NCT00019422

Objectives

1. Determine the objective response rate in patients with recurrent or refractory childhood brain tumors treated with lobradimil and carboplatin.
2. Determine the time to progression in patients treated with this regimen.
3. Assess the toxicity of this regimen in this patient population.
4. Determine the quality of life of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed childhood brain tumor that is recurrent or refractory or for which no standard chemotherapy exists
  • High-grade glioma (anaplastic astrocytoma or glioblastoma multiforme) (High-grade glioma stratum closed to accrual as of 01/08/2002)
  • Low-grade glioma
  • Medulloblastoma/primitive neuroectodermal tumor (PNET)
  • Ependymoma
  • Brainstem tumor or visual pathway glioma (with radiographic evidence only) (Brainstem glioma stratum closed to accrual as of 12/21/2000)



• Evidence of recurrent or progressive disease after front-line therapy documented as an increase in tumor size or appearance of new lesion(s) on MRI



• Patients who did not previously receive radiotherapy as front-line therapy are eligible at time of second recurrence if the first recurrence was treated with radiotherapy only



• Measurable disease in at least 2 dimensions by MRI
  • Diffuse meningeal involvement not considered measurable if it is the only site of disease



• Disease must not be limited to the meninges



• No metastases outside of the CNS

Prior/Concurrent Therapy:

Biologic therapy:

• At least 72 hours since filgrastim (G-CSF)
• No concurrent biologic therapy for brain tumor

Chemotherapy:

• See Disease Characteristics
• No prior carboplatin or lobradimil
• No more than 1 prior chemotherapy regimen for high-grade glioma, low-grade glioma, or ependymoma
• No more than 2 prior chemotherapy regimens for medulloblastoma/PNET
• At least 4 weeks since prior nitrosoureas (2 weeks if also received stem cell/bone marrow rescue)
• At least 2 weeks since any other prior myelosuppressive chemotherapy and recovered
• No other concurrent chemotherapy for brain tumor

Endocrine therapy:

• Concurrent corticosteroids for management of tumor-related edema allowed

Radiotherapy:

• See Disease Characteristics
• At least 6 weeks since prior radiotherapy to measurable disease and recovered
• No concurrent radiotherapy for brain tumor

Surgery:

• No concurrent surgery except for ventriculo-peritoneal shunt placement or revision

Other:

• At least 24 hours since prior vasodilating agents, angiotensin-converting enzyme inhibitors, calcium channel blockers, or beta-blockers

Patient Characteristics:

Age:

• 21 and under at diagnosis

Performance status:

• ECOG 0-2

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute granulocyte count at least 1,000/mm³
• Hemoglobin at least 8.0 g/dL (transfusion allowed)
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGPT no greater than 2.5 times ULN
• No significant hepatic illness

Renal:

• Creatinine within limits as defined below by age:
  • Age 5 and under: less than 1.2 mg/dL
  • Age 6 to 10: less than 1.5 mg/dL
  • Age 11 to 15: less than 1.8 mg/dL
  • Age 16 and over: less than 2.4 mg/dL

Cardiovascular:

• No significant cardiac illness

Pulmonary:

• No significant pulmonary illness

Other:

• No significant systemic illness or organ dysfunction that would preclude study
• No allergic reaction to platinum-containing compounds
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

A maximum of 146 patients will be accrued for this study within 2-4 years.

Outline

This is a multicenter study.

Patients are stratified according to histology (high-grade glioma vs low-grade glioma vs brainstem or visual pathway glioma vs medulloblastoma/primitive neuroectodermal tumor vs ependymoma). (Brainstem glioma stratum closed to accrual as of 12/21/2000.) (High-grade glioma stratum closed to accrual as of 01/08/2002.)

Patients receive carboplatin IV over 15 minutes and lobradimil IV over 10 minutes on days 1 and 2. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 12, patients may receive additional courses at the discretion of the institutional investigator.

Quality of life is assessed at baseline and then every 3 courses.

Patients are followed every 3 months for 1 year or until evidence of disease progression or initiation of a new therapy.

Warren K, Jakacki R, Widemann B, et al.: Phase II trial of intravenous lobradimil and carboplatin in childhood brain tumors: a report from the Children's Oncology Group. Cancer Chemother Pharmacol 58 (3): 343-7, 2006.[PUBMED Abstract]

Warren KE, Patel MC, Aikin AA, et al.: Phase I trial of lobradimil (RMP-7) and carboplatin in children with brain tumors. Cancer Chemother Pharmacol 48 (4): 275-82, 2001.[PUBMED Abstract]

Warren KE, Patel MC, Adamson PC, et al.: Phase I trial of RMP-7 and carboplatin in pediatric patients with brain tumors. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A-764, 1998.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Katherine Warren, MD, Protocol chair		Ph: 301-435-4683

Children's Oncology Group

Regina Jakacki, MD, Protocol chair		Ph: 412-692-7056 Email: regina.jakacki@chp.edu

Registry Information
Official Title		A Phase II Trial of Intravenous Cereport (RMP-7) and Carboplatin in Childhood Brain Tumors
Trial Start Date		1998-03-02
Registered in ClinicalTrials.gov		NCT00019422
Date Submitted to PDQ		1998-03-17
Information Last Verified		2003-04-02
NCI Grant/Contract Number		CA13539