Phase II Randomized Determination of Optimal Hyperfractionated Radiotherapy Dose Combined with BCNU in Supratentorial Malignant Glioma
Basic Trial Information
|Phase II||Treatment||Closed||18 to 70||NCI||RTOG-8302|
I. Determine, in a randomized Phase II study, the most effective radiotherapy dose (64.8 Gy vs. 72.0 Gy vs. 76.8 Gy) delivered in twice-daily fractions of 1.2 Gy in combination with BCNU chemotherapy with regard to improving survival rate and disease-free survival in patients with supratentorial malignant glioma. II. Determine the normal tissue tolerance to hyperfractionation delivered at 1.2 Gy twice daily with 4-8 hours between fractions to total doses of 64.8 Gy in 54 fractions, 72.0 Gy in 60 fractions, and 76.8 Gy in 64 fractions. Both acute and delayed radiation will be scored.
See General Eligibility Criteria
See General Eligibility Criteria
General Eligibility Criteria:
Patients aged 18-70 years with a tissue diagnosis of glioblastoma multiforme (with areas of necrosis), malignant astrocytoma, or astrocytoma with foci of anaplasia whose tumor is confined to the supratentorial area. Therapy must be initiated within 4 weeks of surgery, after recovery from the effects of surgery. Patients may not have received prior radiotherapy to the head or neck, chemotherapy, or radiosensitizer therapy. The estimated survival must be at least 8 weeks and the Karnofsky performance status at least 60. Hematologic, renal, hepatic, and pulmonary functions should be adequate. A diagnostic CT scan must be performed postoperatively prior to the initiation of radiotherapy. Patients with well differentiated astrocytomas, multifocal malignant gliomas, and recurrent malignant gliomas are ineligible, as are patients with metastases below the tentorium or beyond the cranial vault. Per May 1987 amendment, patients with acquired immune deficiency syndrome are not eligible.
101 patients per arm will be required. As of June 1989, 50 additional patients will be entered (25 to Arm II and 25 to Arm V) to attain approximately 175 patients per Arm. At the present accrual rate of 9-10 patients per month, accrual should be completed in October 1989.
As of June 1989, patients are randomized 1:1 to Arms II and V. Arm I (Closed October 1985): Radiotherapy plus Single-agent Chemotherapy. BCNU, NSC-409962; tumor irradiation using megavoltage equipment (Co-60 up to and including 10 MeV photons). Total Radiotherapy dose 64.8 Gy. Arm II: Radiotherapy plus Single-agent Chemotherapy. BCNU. Total Radiotherapy dose 72.0 Gy. Arm III (Closed February 1986): Radiotherapy plus Single-agent Chemotherapy. BCNU. Total Radiotherapy dose 76.8 Gy. Arm IV (added per October 1985 amendment; closed December 1987): Radiotherapy plus Single-agent Chemotherapy. BCNU. Total Radiotherapy dose 81.6 Gy. Arm V (added in September 1987): Radiotherapy plus Single-agent Chemotherapy. BCNU. Total Radiotherapy dose 48 Gy. Arm VI (added in September 1987; closed June 1989): Radiotherapy plus Single-agent Chemotherapy. BCNU. Total Radiotherapy dose 54.4 Gy.
Donahue B, Scott CB, Nelson JS, et al.: Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02. Int J Radiat Oncol Biol Phys 38 (5): 911-4, 1997.[PUBMED Abstract]
Donahue B, Scott C, Nelson J, et al.: Influence of an oligodendrogliomal component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02. Int J Radiat Oncol Biol Phys 36 (suppl 1): A-5, 161, 1996.
Nelson JS, Petito CK, Scott CB, et al.: High cell density and nuclear pleomorphism do not predict shortened survival in oligodendroglial tumors: report from Radiation Therapy Oncology Group study 8302. J Neuropathol Exp Neurol 55(5): A-134, 638, 1996.
Werner-Wasik M, Scott CB, Nelson DF, et al.: Final report of a phase I/II trial of hyperfractionated and accelerated hyperfractionated radiation therapy with carmustine for adults with supratentorial malignant gliomas. Radiation Therapy Oncology Group Study 83-02. Cancer 77 (8): 1535-43, 1996.[PUBMED Abstract]
Murray KJ, Nelson DF, Scott C, et al.: Quality-adjusted survival analysis of malignant glioma. Patients treated with twice-daily radiation (RT) and carmustine: a report of Radiation Therapy Oncology Group (RTOG) 83-02. Int J Radiat Oncol Biol Phys 31 (3): 453-9, 1995.[PUBMED Abstract]
Scott CB, Nelson JS, Farnan NC, et al.: Central pathology review in clinical trials for patients with malignant glioma. A Report of Radiation Therapy Oncology Group 83-02. Cancer 76 (2): 307-13, 1995.[PUBMED Abstract]
Werner-Wasik M, Scott C, Curran W, et al.: Final report of a phase I/II trial of hyperfractionated (HF) and accelerated hyperfractionated (AHF) radiation therapy with carmustine for adults with supratentorial malignant gliomas: RTOG 83-02. [Abstract] Proceedings of the American Radium Society 78: A40, 25, 1995.
Curran WJ Jr, Scott CB, Weinstein AS, et al.: Survival comparison of radiosurgery-eligible and -ineligible malignant glioma patients treated with hyperfractionated radiation therapy and carmustine: a report of Radiation Therapy Oncology Group 83-02. J Clin Oncol 11 (5): 857-62, 1993.[PUBMED Abstract]
Chinnaiyan P, Wang M, Rojiani AM, et al.: The prognostic value of nestin expression in newly diagnosed glioblastoma: report from the Radiation Therapy Oncology Group. Radiat Oncol 3: 32, 2008.[PUBMED Abstract]
Chakravarti A, Seiferheld W, Tu X, et al.: Immunohistochemically determined total epidermal growth factor receptor levels not of prognostic value in newly diagnosed glioblastoma multiforme: report from the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 62 (2): 318-27, 2005.[PUBMED Abstract]
Seiferheld W, Chakravarti A, Ang KK, et al.: Overexpression of the epidermal growth factor receptor (EGFR), as determined by EGFR immunostaining on tissue microarrays, fails to demonstrate prognostic value for patients with glioblastoma multiforme: a report from RTOG 7401, 7918, 8302, 8409, 9006, 9305, 9602, and 9806. [Abstract] Int J Radiat Oncol Biol Phys 54(2 suppl 1): A-166, 616, 2002.
Prados MD, Scott C, Curran WJ Jr, et al.: Procarbazine, lomustine, and vincristine (PCV) chemotherapy for anaplastic astrocytoma: A retrospective review of radiation therapy oncology group protocols comparing survival with carmustine or PCV adjuvant chemotherapy. J Clin Oncol 17 (11): 3389-95, 1999.[PUBMED Abstract]
Nelson JS, Scott CB, Constine LS, et al.: Alzheimer related lesions (ARL) and neural morbidity in glioblastoma (GBM): patients data from Radiation Oncology Group (RTOG) glioma trials. [Abstract] Lab Invest 78 : A-942, 161a, 1998.
Prados MD, Scott CB, Rotman M, et al.: Influence of bromodeoxyuridine radiosensitization on malignant glioma patient survival: a retrospective comparison of survival data from the Northern California Oncology Group (NCOG) and Radiation Therapy Oncology Group trials (RTOG) for glioblastoma multiforme and anaplastic astrocytoma. Int J Radiat Oncol Biol Phys 40 (3): 653-9, 1998.[PUBMED Abstract]
Simpson JR, Horton J, Scott C, et al.: Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat Oncol Biol Phys 26 (2): 239-44, 1993.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations
Radiation Therapy Oncology Group
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.