Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Computer Planned Radiation Therapy Plus Chemotherapy in Treating Patients With Glioblastoma Multiforme

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Completed	18 and over	NCI	RTOG-9803 NCT00003417, RTOG-98-03

Objectives

1. Determine the feasibility and toxicity of escalating doses of conformal radiotherapy planned with 3-D treatment planning plus carmustine in patients with glioblastoma multiforme.
2. Determine dose/volume and dose/anatomic characteristics that influence radiotherapy-induced CNS toxicity.
3. Evaluate local control, survival, and failure patterns of these patients treated with high doses of conformal radiotherapy to gross disease.
4. Correlate changes on cross-sectional diagnostic MRI imaging studies to clinical or biologic endpoints.

Entry Criteria

Disease Characteristics:

• Histologically confirmed glioblastoma multiforme with areas of necrosis as diagnosed by surgical biopsy or subtotal excision
  • Supratentorial tumor



• Gross measurable residual disease



• No well-differentiated or anaplastic astrocytoma, multifocal glioma, or recurrent glioblastoma multiforme



• Therapy must begin within 5 weeks after surgery but within 1 week after registration



• CT or MRI scan preoperatively and MRI postoperatively prior to initiation of radiotherapy
  • If undergoing a stereotactic-guided needle biopsy, not required to repeat MRI after procedure if the prebiopsy MRI is suitable for treatment planning



• Prior complete surgical resection of tumor allowed

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to head or neck

Surgery:

• See Disease Characteristics

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin no greater than 2 mg/dL
• SGPT or SGOT no greater than 2 times normal

Renal:

• BUN no greater than 30 mg/dL
• Creatinine no greater than 1.8 mg/dL

Pulmonary:

• Normal chest x-ray

  OR

• DLCO at least 60% predicted

Other:

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except carcinoma in situ of the cervix or bladder, ductal carcinoma in situ of the breast, or nonmelanomatous skin cancer
• Neurologic functional status 0-3
• No major medical illness or psychiatric impairments that would preclude study participation

Expected Enrollment

A total of 40 patients (20 per arm) will be accrued for this study within at least 5 months.

Outline

This is a dose-escalation study. Patients are stratified according to the planned target volume, i.e., gross residual tumor plus 3 mm (less than 75 cc vs at least 75 cc).

Patients undergo radiotherapy over 15-30 minutes daily 5 days a week for 6-8 weeks. After 46 Gy of radiotherapy have been administered, patients undergo radiotherapy field reduction and are accrued into one of four dose levels. (Dose level 1 closed to accrual 1/16/01) All patients receive at least 33 radiation treatments. Each patient is evaluated for acute dose-limiting toxicity for 90 days from start of therapy.

Patients also receive carmustine IV over 1-2 hours daily on days 1-3 for the first week of radiotherapy. Treatment repeats every 8 weeks for up to 6 courses.

Patients are followed every 4 months for 2 years, every 6 months for 1 year, and then annually thereafter.

Tsien C, Moughan J, Michalski JM, et al.: Phase I three-dimensional conformal radiation dose escalation study in newly diagnosed glioblastoma: Radiation Therapy Oncology Group Trial 98-03. Int J Radiat Oncol Biol Phys 73 (3): 699-708, 2009.[PUBMED Abstract]

Fox W, Berkey B, Michalski J, et al.: Health-related quality of life and cognitive status in patiens with glioblastoma multiforme receiving escalating doses of comformal three-dimensional radiation on RTOG 9803. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppll 1): A-128, S78, 2005.

Werner-Wasik M, Seiferheld W, Michalski J, et al.: Phase I/II conformal three-dimensional radiation therapy dose escalation study in patients with supratentorial glioblastoma multiforme: report of the Radiation Therapy Oncology Group 98-03 protocol. [Abstract] Int J Radiat Oncol Biol Phys 60 (1 Suppl 1): A-58, S163-4, 2004. Available online. Last accessed January 27, 2005.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Jeff Michalski, MD, Protocol chair		Ph: 314-362-8566; 800-600-3606 Email: jmichalski@radonc.wustl.edu

Registry Information
Official Title		Phase I/II Radiation Dose Escalation Study Applying Conformal Radiation Therapy in Supratentorial Glioblastoma Multiforme
Trial Start Date		1998-09-08
Trial Completion Date		2009-03-01
Registered in ClinicalTrials.gov		NCT00003417
Date Submitted to PDQ		1998-07-08
Information Last Verified		2003-09-21
NCI Grant/Contract Number		CA21661