Radiation Therapy With or Without Radiosurgery in Treating Patients With Brain Metastases

• ClinicalTrials.gov Identifier: NCT00002708
• Recruitment Status: Completed
• First Posted: April 13, 2004
• Last Update Posted: November 19, 2013
• Sponsor: Radiation Therapy Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Radiation Therapy Oncology Group

Tracking Information

• First Submitted Date: November 1, 1999
• First Posted Date: April 13, 2004
• Last Update Posted Date: November 19, 2013
• Study Start Date: January 1996
• Actual Primary Completion Date: January 2002 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures: Not Provided
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Radiation Therapy With or Without Radiosurgery in Treating Patients With Brain Metastases
• Official Title: A PHASE III TRIAL COMPARING WHOLE BRAIN IRRADIATION WITH VERSUS WITHOUT STEREOTACTIC RADIOSURGERY BOOST FOR PATIENTS WITH ONE TO THREE UNRESECTED BRAIN METASTASES

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether giving radiation therapy during surgery is more effective than standard radiation therapy in treating brain metastases.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or without radiosurgery in treating patients with brain metastases that cannot be removed during surgery.

Detailed Description

OBJECTIVES: I. Compare the overall survival of patients with one unresected brain metastasis treated with conventional whole brain radiotherapy (WBRT) with vs. without a stereotactic radiosurgery (SRS) boost. II. Compare sites of recurrence and cause of death in these patients treated with WBRT followed by SRS vs. WBRT alone.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center and extracranial disease (yes or no). Patients are randomized to one of two treatment arms. Arm I: Patients receive fractionated external beam whole brain irradiation (WBRT) 5 days each week for 3 weeks. Both portals are treated during each radiotherapy session. Patients who still have a solitary lesion with a diameter no greater than 4.0 cm also receive stereotactic radiosurgery within 7 days of completing WBRT. Arm II: Patients receive WBRT only. Patients are followed every 3 months for 1 year, then every 4 months for 2 years, and then annually.

PROJECTED ACCRUAL: A total of 262 patients will be accrued over 2.5-3.75 years for this study. The study may close early if interim analysis after 33% and 67% of patients have been followed for 6 months produces significant results. After 6/14/99 an additional 46 patients with a solitary brain metastasis only will be accrued.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Cancer

Intervention

• Procedure: surgical procedure
• Radiation: radiation therapy
• Radiation: stereotactic radiosurgery

Study Arms

• Experimental: Arm 1
  Whole brain radiation therapy (WBRT) to 37.5 Gy/15 fractions/2.5 Gy once daily, 5 days/week followed by radiosurgery to all metastases
  Interventions:

  • Procedure: surgical procedure
  • Radiation: radiation therapy
  • Radiation: stereotactic radiosurgery
• Active Comparator: Arm 2
  WBRT to 37.5 Gy/15 fractions/2.5 Gy once daily, 5 days/week
  Intervention: Radiation: radiation therapy

Publications *

• Hazard LJ, Jensen RL, Shrieve DC. Role of stereotactic radiosurgery in the treatment of brain metastases. Am J Clin Oncol. 2005 Aug;28(4):403-10. Review.
• Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May 22;363(9422):1665-72.
• Sperduto PW, Scott C, Andrews D: Stereotactic radiosurgery with whole brain radiation therapy improves survival in patients with brain metastases: report of Radiation Therapy Oncology Group phase III study 95-08. [Abstract] Int J Radiat Oncol Biol Phys 54(2 suppl 1): 3, 2002.
• Sperduto P, Scott C, Andrews D, et al.: Preliminary report of RTOG 95-08: a phase III trial comparing whole brain irradiation alone versus whole brain irradiation plus stereotactic radiosurgery for patients with two or three unresected brain metastases. [Abstract] Int J Radiat Oncol Biol Phys 48: A-6, 113, 2000.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 18, 2013): 333
• Original Enrollment: Not Provided
• Actual Study Completion Date: December 2004
• Actual Primary Completion Date: January 2002 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS: No more than 1 unresected or subtotally resected brain metastasis lesion from histologically confirmed systemic malignancy Eligible only if surgical resection refused by patient or resection deemed inappropriate by patient's physician 1 intraparenchymal metastasis clearly defined on contrast enhanced MRI Maximum diameter of lesion no greater than 4.0 cm No leukemia or lymphoma Extracranial sites of primary metastatic disease allowed if no clinical or radiographic evidence of progression within 1 month prior to entry No metastasis to brainstem, midbrain, pons, or medulla No leptomeningeal metastasis by MRI or CSF evaluation No metastasis within 10 mm of optic nerves and chiasm (area must be excluded from high dose stereotactic radiosurgery boost field)

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: 70-100% Karnofsky Hematopoietic: Absolute neutrophil count at least 1,000/mm3 Platelet count at least 50,000/mm3 Hemoglobin at least 8 g/dL Hepatic: Not specified Renal: Not specified Other: Neurologic status 0-2 No major medical or psychiatric contraindication to protocol entry Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No concurrent chemotherapy for systemic cancer Endocrine therapy: Concurrent hormonal therapy, including tamoxifen, allowed Radiotherapy: No prior cranial radiotherapy Surgery: Prior subtotal resection allowed Other: No other concurrent treatment for brain metastasis until recurrence

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00002708
• Other Study ID Numbers: RTOG-9508; CDR0000064522
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Radiation Therapy Oncology Group
• Original Responsible Party: Not Provided
• Current Study Sponsor: Radiation Therapy Oncology Group
• Original Study Sponsor: National Cancer Institute (NCI)
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: David W. Andrews, MD, FACS; Sidney Kimmel Cancer Center at Thomas Jefferson University

• PRS Account: Radiation Therapy Oncology Group
• Verification Date: November 2013