Phase 3
N=230
Radiation Therapy Combined With Chemotherapy in Treating Patients With Anaplastic Astrocytoma or Mixed Gliomas
Brain and Central Nervous System Tumors
Bottom Line
View on ClinicalTrials.gov: NCT00004259 ↗Enrolled (actual)
230
Serious AEs
60.1%
Results posted
Nov 2017
Primary outcome: Primary: (Phase III) Overall Survival (OS) — 3.9; 3.8 years — p=0.36
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- BCNU 80mg/m2 (Drug); TMZ 200mg/m2 (Drug); radiation therapy (Radiation); CCNU (Drug); BCNU 150mg/m2 (Drug); BCNU 200mg/m2 (Drug); TMZ 150mg/m2 six 6-week cycles (Drug); TMZ 150mg/m2 six 8-week cycles (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Radiation Therapy Oncology Group
- Primary completion
- Feb 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY (Phase III) Overall Survival (OS) |
3.9; 3.8 | 0.36 |
| PRIMARY (Phase I) Number of Subjects With Dose Limiting Toxicities (DLT) on the Two Pilot Arms |
1; 0; 4; 3 | — |
| SECONDARY (Phase III) Time to Tumor Progression (TTP) |
45.4; 54.7 | 0.46 |
| SECONDARY (Phase III) Number of Patients With Grade 3 or Higher Toxicity |
46; 75; 31; 34 | <0.001 sig |
| SECONDARY (Phase III) Survival Time by MGMT Status |
7.2; 3.1 | 0.08 |
| SECONDARY (Phase III) Progression-free Survival by MGMT Status |
4.0; 2.1 | 0.41 |
Summary
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as temozolomide, carmustine, and lomustine, use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells.
PURPOSE: This randomized phase III trial is studying radiation therapy and temozolomide to see how well they work compared to radiation therapy and carmustine or lomustine in treating patients with anaplastic astrocytoma or mixed gliomas.
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Histologically proven unifocal anaplastic astrocytoma or mixed gliomas, including the following:
- Anaplastic astrocytoma
- Mixed oligodendroglial/astrocytic tumors
- Oligodendroglial component must be no greater than 25%
- No vascular proliferation and necrosis
- Increased cellularity, pleomorphism, and nuclear atypia allowed
- No tumor predominantly located in the posterior fossa (i.e., brainstem or cerebellum)
- Patients with prior biopsy proven low grade astrocytoma who now have anaplastic astrocytoma and have had no prior radiotherapy or chemotherapy also eligible
- Study therapy must begin within 6 weeks of diagnosis
- No spinal cord tumors, spinal drop metastases, or metastases to noncontiguous meninges
- Pathologic evidence of local meningeal infiltration by underlying tumor allowed
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Karnofsky 60-100%
Life expectancy:
- At least 1 year
Hematopoietic:
- Hemoglobin at least 10 g/dL
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 150,000/mm^3
Hepatic:
- Bilirubin less than 2 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST) less than 2 times ULN
- Alkaline phosphatase less than 2 times ULN
Renal:
- Blood urea nitrogen no greater than 25 mg/dL
- Creatinine less than 1.5 times normal
Pulmonary:
- No pre-existing lung disease that, in the investigator's opinion, would preclude administration of carmustine or lomustine or completion of therapy
Other:
- No other major medical illness or psychiatric impairment that would preclude study compliance
- No other malignancy within the past 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix
- No known hypersensitivity to 1 of the components of carmustine, lomustine, temozolomide, dacarbazine, or any other nitrosourea
- No active infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No prior biologic therapy
Chemotherapy:
- See Disease Characteristics
- No prior chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- See Disease Characteristics
- No prior radiotherapy to brain or head and neck
Surgery:
- Not specified
Other:
- No other concurrent anticancer treatment for anaplastic astrocytoma until a recurrence is detected
Data sourced from ClinicalTrials.gov (NCT00004259). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.