Carboplatin, Vincristine, and Temozolomide in Treating Children With Progressive and/or Symptomatic Low-Grade Glioma

Children's Oncology Group

Status: Completed

Conditions: Brain Tumor; Central Nervous System Tumor

Treatments: Drug: vincristine sulfate; Drug: carboplatin; Drug: temozolomide

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00077207

CDR0000350005 (Other Identifier)

NCI-2012-02572 (Other Identifier)

ACNS0223

COG-ACNS0223 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as carboplatin, vincristine, and temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug may kill more tumor cells.

PURPOSE: This pilot study is studying giving carboplatin and vincristine together with temozolomide in treating children with progressive and/or symptomatic low-grade glioma.

Full description

OBJECTIVES:

Primary

• Determine the feasibility and toxicity of an induction and maintenance regimen comprising carboplatin, vincristine, and temozolomide in children with progressive and/or symptomatic low-grade gliomas.

Secondary

• Determine response rate in patients treated with this regimen.
• Determine 3-year progression-free survival and overall survival of patients treated with this regimen.
• Correlate response and progression-free survival with the genomic profile of tumors in patients treated with this regimen.

OUTLINE: This is a pilot study.

• Induction therapy: Patients receive carboplatin IV over 1 hour on days 1, 8, 15, and 22; vincristine IV on days 1, 8, 15, 22, 29, and 36; and oral temozolomide on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy.
• Maintenance therapy: Patients receive carboplatin and temozolomide as in induction therapy and vincristine IV on days 1, 8, and 15. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 30-50 patients will be accrued for this study within 2 years.

Enrollment: 66 patients

Sex: All

Ages: Under 10 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed progressive and/or symptomatic low-grade glioma, including any of the following:

  • WHO grade I or II astrocytoma
  • Grade I or II oligodendrogliomas
  • Mixed oligodendrogliomas
  • Gangliogliomas

• Measurable disease

• Progressive and/or symptomatic supratentorial or spinal cord tumors that cannot be removed for anatomical reasons are allowed

• Optic pathway tumors allowed provided there is evidence of progressive disease by MRI and/or symptoms of deteriorating vision, progressive hypothalamic/pituitary dysfunction, or diencephalic syndrome

• Dorsally exophytic brainstem gliomas that were previously resected more than 50% are allowed provided the residual tumor shows progression (with or without symptoms)

• No diffuse brain stem tumors

• No type 1 neurofibromatosis

PATIENT CHARACTERISTICS:

Age

• 10 and under

Performance status

• ECOG 0-2
• Lansky 50-100%

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin ≥ 8.0 gm/dL
• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT < 2.5 times ULN

Renal

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
• Creatinine ≤ 0.8 mg/dL (age 5 and under) OR ≤ 1.0 mg/dL (age 6 to10)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunomodulating agents

Chemotherapy

• No other concurrent anticancer chemotherapy

Endocrine therapy

• Prior corticosteroids allowed
• No concurrent corticosteroids except for the treatment of increased intracranial pressure

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics
• Prior surgery allowed

Other

• No other prior therapy

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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66 participants in 1 patient group

Treatment (carboplatin, vincristine sulfate, temozolomide)

Experimental group

Description:

Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression.

Treatment:

Drug: temozolomide

Drug: vincristine sulfate

Drug: carboplatin