Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Newly Diagnosed Brain Stem Glioma
- Conditions
- Brain TumorsCentral Nervous System Tumors
- Interventions
- Registration Number
- NCT00003625
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 7
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Stratum 1 radiation therapy 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. Stratum 1 etoposide 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. Stratum 1 vincristine sulfate 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. Stratum 1 cyclosporine 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.
- Primary Outcome Measures
Name Time Method Event Free Survival
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (74)
University of Alabama Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
University of California San Diego Cancer Center
🇺🇸La Jolla, California, United States
Lucile Packard Children's Hospital at Stanford
🇺🇸Palo Alto, California, United States
Sutter Cancer Center
🇺🇸Sacramento, California, United States
Kaiser Permanente-Southern California Permanente Medical Group
🇺🇸San Diego, California, United States
Naval Medical Center - San Diego
🇺🇸San Diego, California, United States
Kaiser Permanente Medical Center - Santa Clara
🇺🇸Santa Clara, California, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
Scroll for more (64 remaining)University of Alabama Comprehensive Cancer Center🇺🇸Birmingham, Alabama, United States