Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Newly Diagnosed Brain Stem Glioma

Children's Oncology Group

Status and phase: Completed; Phase 1

Conditions: Central Nervous System Tumors; Brain Tumors

Treatments: Radiation: radiation therapy; Drug: vincristine sulfate; Drug: cyclosporine; Drug: etoposide

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00003625

9879

CDR0000066706

POG-9879

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus radiation therapy in treating patients with newly diagnosed brain stem glioma.

Full description

OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of vincristine given as an IV push dose in combination with continuous infusion cyclosporine and oral etoposide concurrent with and prior to radiotherapy in children with newly diagnosed primary intrinsic brain stem glioma. II. Determine the incidence and severity of other toxicities of vincristine in this regimen in these patients. III. Determine a safe and tolerable dose of vincristine under these conditions to be used in phase II studies. IV. Seek preliminary evidence of antitumor activity in this setting in these patients.

OUTLINE: This is dose escalation study of vincristine. Patients receive radiotherapy daily for 6 weeks with concurrent induction chemotherapy. Induction chemotherapy consists of vincristine IV push weekly for 6 weeks, oral etoposide daily on days 1-21 and 29-49 and cyclosporine IV over 2 hours prior to vincristine followed by a continuous 36 hour infusion. Cohorts of 3-6 patients receive escalating doses of vincristine. If dose limiting toxicity (DLT) occurs in 2 or more of 3-6 patients, the maximum tolerated dose (MTD) has been exceeded and the preceding dose is declared the MTD. Maintenance therapy consists of 6 monthly courses of cyclosporine IV over 36 hours beginning on day 1, vincristine IV push on day 1, and oral etoposide daily for days 1-21. Patients are followed every 6 months for 4 years and then annually thereafter.

PROJECTED ACCRUAL: At least 6 patients will be accrued into this study at a rate of 12 patients per year.

Enrollment: 7 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 glioma by MRI Biopsy is neither necessary nor encouraged A least two-thirds of the tumor is in the pons Origin of the tumor is clearly in the pons Must be registered within 28 days of diagnosis Clinical history less than 6 months duration (cranial nerve deficit, long tract signs, or ataxia) No diffuse leptomeningeal disease

PATIENT CHARACTERISTICS: Age: 3 to 21 Performance status: Karnofsky or Lansky 50-100% Life expectancy: At least 6 weeks Hematopoietic: Absolute neutrophil count at least 1,000/mm3 Platelet count at least 75,000/mm3 Hepatic: SGPT less than 2 times normal Renal: Creatinine normal for age OR Creatinine clearance greater than 70 mL/min

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy Chemotherapy: No prior chemotherapy No other concurrent chemotherapy Endocrine therapy: Prior steroids at stable or decreasing doses allowed Radiotherapy: No prior radiotherapy Surgery: Not specified Other: No other concurrent investigational agents

Trial design

7 participants in 1 patient group

Stratum 1

Experimental group

Description:

Concomitant irradiation and vincristine sulfate in esc dose beginning with 0.8 mg/m2, etoposide and Cyclosporine A given over 6 weeks, then monthly maint courses over 6 mths, with no clinical and radiologic progression. Stable disease indicates continuation of therapy. Clinical deterioration within 4 months of completion of radiation therapy must be confirmed to be PD by imaging. Clinical progression even in the absence of imaging changes will be accepted as reflecting disease progression. Steroids dexamethasone (Decadron) given as clinically indicated and tapered as tolerated. Steroids may decrease capillary permeability to chemotherapeutic agents and antagonise the effect of cyclosporin A. Also contributes to the syndrome of seizures and white matter changes seen with cyclosporine in the post BMT period. If steroid use is required, the recommended schedule of Decadron dosing during the 6 week induction course is 8 mg/m2 divided q 6-8 hours.

Treatment:

Drug: etoposide

Radiation: radiation therapy

Drug: cyclosporine

Drug: vincristine sulfate