Radiation Therapy Plus Carboplatin and Lobradimil in Treating Children With Newly Diagnosed Brain Stem Gliomas

Children's Oncology Group

Status and phase: Completed; Phase 1

Conditions: Brain and Central Nervous System Tumors

Treatments: Drug: cereport; Drug: carboplatin; Radiation: radiation therapy

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00005602

ALK-01-042

COG-ADVL0012 (Other Identifier)

CCG-ADVL0012 (Other Identifier)

CCG-09802 (Other Identifier)

ADVL0012

CDR0000067715 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as carboplatin and lobradimil may make the tumor cells more sensitive to radiation therapy.

PURPOSE: Phase I trial to study the effectiveness of combining radiation therapy with carboplatin and lobradimil in treating children who have newly diagnosed brain stem gliomas.

Full description

OBJECTIVES:

• Determine the maximum tolerated duration of lobradimil plus carboplatin with radiotherapy in patients with newly diagnosed brain stem gliomas.
• Determine the toxic effects of this treatment regimen in these patients.
• Assess the response to radiotherapy in patients treated with this regimen.

OUTLINE: Patients receive radiotherapy for 5 consecutive days a week for 6.5 weeks, for a total of 33 doses. Patients receive carboplatin IV over 15 minutes followed by lobradimil IV over 10 minutes concurrently with radiotherapy.

The first cohort of 3-6 patients receives treatment with carboplatin and lobradimil for the first three weeks of radiotherapy, with the duration of chemotherapy increasing by one week with each subsequent cohort until the maximum duration of 6.5 weeks is reached or until unacceptable toxicity occurs in 2 of 6 patients.

Patients are followed at 6 weeks; every 3 months for 2 years; every 6 months for 3 years; and then annually thereafter.

PROJECTED ACCRUAL: A total of 15-24 patients will be accrued for this study within 36 months.

Enrollment: 13 patients

Sex: All

Ages: 3 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Newly diagnosed diffuse, intrinsic brain stem gliomas

• Measurable disease

• No disseminated disease at sites other than brain stem

• No neurofibromatosis

• Treatment must begin within 31 days of diagnosis

  • Date of diagnosis will be considered date of surgery in patients undergoing surgical biopsy

PATIENT CHARACTERISTICS:

Age:

• 3 to 21

Performance status:

• Karnofsky 50-100% (over 10 years of age)
• Lansky 50-100% (10 years of age and under)

Life expectancy:

• At least 2 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGPT no greater than 2.5 times ULN (4.0 times ULN with antiepileptic or steroid medications)

Renal:

• Creatinine less than ULN for age OR
• Creatinine clearance or glomerular filtration rate greater than 80 mL/min

Other:

• No history of severe allergic reaction to any platinum-containing compound
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent growth factors during therapy with carboplatin

Chemotherapy

• Not specified

Endocrine therapy

• Prior corticosteroids for brain stem glioma are allowed

Radiotherapy

• Not specified

Surgery

• Prior surgery for brain stem glioma is allowed

Other

• At least 24 hours since any of the following medications:

  • Vasodilating compounds
  • Angiotensin-converting enzyme inhibitors
  • Calcium channel blockers
  • Beta blockers

• No other prior therapy for brain stem glioma

Trial design

13 participants in 4 patient groups

Radiation Therapy, 33 Doses; Carboplatin 35mg^m2 for 20 Days

Experimental group

Treatment:

Drug: carboplatin

Drug: cereport

Radiation: radiation therapy

Radiation Therapy, 33 Doses; Carboplatin 35mg^m2 for 25 Days

Experimental group

Treatment:

Drug: carboplatin

Drug: cereport

Radiation: radiation therapy

Radiation Therapy, 33 Doses; Carboplatin 35mg^m2 for 30 Days

Experimental group

Treatment:

Drug: carboplatin

Drug: cereport

Radiation: radiation therapy

Radiation Therapy, 33 Doses; Carboplatin 35mg^m2 for 33 Days

Experimental group

Treatment:

Drug: carboplatin

Drug: cereport

Radiation: radiation therapy