Vinblastine and Carboplatin in Treating Young Patients With Newly Diagnosed or Recurrent Low-Grade Glioma

OBJECTIVES:

Primary

• Estimate the maximum tolerated dose and recommended phase II dose of vinblastine when given in combination with carboplatin in pediatric patients with newly diagnosed or recurrent low-grade gliomas.
• Define and describe the acute and dose-limiting toxicities of this regimen.
• Describe the toxicities associated with repeated courses of the combination chemotherapy regimen and the number of treatment modifications required over the course of treatment.

Secondary

• Describe the radiographic responses in patients treated with this regimen.
• Describe changes in diffusion/perfusion imaging during study therapy.

OUTLINE: This is a multicenter, dose-escalation study of vinblastine. Patients are stratified according to amount of prior therapy (heavily pretreated vs less heavily pretreated).

Patients receive carboplatin IV over 30 minutes on day 1 and vinblastine IV on days 1, 8, 15. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of vinblastine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed* low-grade glioma, including 1 of the following subtypes:

• Astrocytoma variants

• Fibrillary, protoplasmic, or mixed
• Pilocytic astrocytoma, including pilomyxoid variants
• Pleomorphic xanthoastrocytoma
• Infantile desmoplastic astrocytoma
• Ganglioglioma
• Oligodendroglial tumors
• Mixed glioma, including oligoastrocytoma NOTE: *Biopsy not required for patients who have visual pathway tumors involving the optic nerves and/or optic radiations (i.e., not isolated to the hypothalamus/chiasm)
• Biopsy proven focal low-grade gliomas of the brainstem with measurable disease allowed

• No diffuse, intrinsic brainstem tumors
• Residual tumor visible on MRI
• Patients without NF-1 must meet the following criteria:

• Progressive disease after surgery/biopsy based on clear radiographic or clinical evidence of progression OR gross residual tumor (> 1.5 cm²) after surgery/biopsy that is felt to be a high risk to the patient for neurologic and/or visual impairment if the tumor progresses
• Visual pathway tumors that are not isolated to the hypothalamus/chiasm and are not biopsied must be a high risk to the patient for neurologic and/or visual impairment
• Patients with NF-1 must have evidence of radiographic progression on MRI and/or clinical worsening (e.g., worsening of ophthalmologic exam for visual pathway tumors)
• Meets 1 of the following criteria:

• Newly diagnosed disease
• Recurrent disease
• No ventriculoperitoneal shunt-related ascites

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 50-100% (for patients > 10 years of age) OR Lansky PS 50-100% (for patients ≤ 10 years of age)
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³ (transfusion independent)
• Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine based on age, as follows:

• No greater than 0.8 mg/dL (for patients ≤ 5 years of age)
• No greater than 1.0 mg/dL (for patients 6-10 years of age)
• No greater than 1.2 mg/dL (for patients 11-15 years of age)
• No greater than 1.5 mg/dL (for patients > 15 years of age)
• Bilirubin ≤ 1.5 times upper limit of normal
• ALT ≤ 110 U/L
• Albumin ≥ 2 g/dL
• No history of allergy to carboplatin
• No hyponatremia requiring treatment
• No uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior therapy except for corticosteroids and surgery (for patients with newly diagnosed disease)
• Prior chemotherapy and/or radiotherapy in addition to surgery and corticosteroids allowed (for patients with recurrent disease)
• Prior carboplatin and/or vinblastine allowed if there was no evidence of progressive disease while on therapy and there were no dose reductions due to toxicity (for patients with recurrent disease)
• At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered (for patients with recurrent disease)
• At least 7 days since prior hematopoietic growth factors (for patients with recurrent disease)
• At least 7 days since prior biological agents (for patients with recurrent disease)
• At least 9 months since prior external beam radiotherapy or gamma knife therapy that included all target lesions (i.e., there is no restriction if a new lesion arises outside the radiation field or a nonirradiated lesion progresses) and recovered (for patients with recurrent disease)
• No other concurrent investigational drugs
• No other concurrent anticancer agents
• No other concurrent chemotherapy, radiotherapy, immunotherapy, or biological therapy
• No concurrent corticosteroids for antiemesis
• Concurrent steroids allowed for tumor edema/increased intracranial pressure provided dose of dexamethasone is stable or decreasing for the past 7 days
• Concurrent physiologic or stress doses of steroids allowed for endocrine deficiencies