Official Title: “Phase III Trial on Convergent Beam Irradiation of Cerebral Metastases”

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Adjuvant radiation therapy may kill any remaining tumor cells following surgery or radiosurgery for brain metastases.

PURPOSE: This randomized phase III trial is studying surgery or radiosurgery alone to see how well it works compared to surgery or radiosurgery and whole-brain radiation therapy in treating brain metastases in patients with solid tumors.

Study Type: Interventional

Study Design: Treatment, Randomized, Active Control

OBJECTIVES:

Primary - Investigate the efficacy and toxicity of adjuvant whole brain radiotherapy after prior surgical resection or radiosurgery of 1 to 3 brain metastases from solid tumor in patients with good performance status and controlled systemic cancer.

Secondary - Determine overall survival and progression-free survival of patients treated on this protocol. - Determine time to neurologic progression in patients treated on this protocol. - Determine quality of life of patients treated on this protocol.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by participating center, number of brain metastases (single vs multiple), type of primary tumor (stable systemic cancer vs synchronous or unknown primary), WHO performance status (0-1 vs 2), and treatment (prior surgical resection vs planned radiosurgery).

Patients who have undergone complete surgical resection are randomized to 1 of 2 treatment arms within 4 weeks after surgery. - Arm I: Patients undergo adjuvant whole brain radiotherapy (WBRT). - Arm II: Patients do not receive adjuvant radiotherapy. Patients planning to undergo radiosurgery are randomized to 1 of 2 treatment arms. - Arm III: Patients undergo radiosurgery followed by adjuvant WBRT within 4 weeks after surgery. - Arm IV: Patients undergo radiosurgery alone. Quality of life is assessed at baseline, at 8 weeks, and then every 3 months thereafter.

After completion if study treatment, patients are followed at 8 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 340 patients (85 per treatment arm) will be accrued for this study within 3.5 years.

Intervention(s) in this Clinical Trial

• Procedure: adjuvant therapy
• Procedure: radiation therapy
• Procedure: stereotactic radiosurgery

Primary Measures

• Survival with a WHO performance status 0-2 as measured by Logrank at 8 weeks after completion of study treatment, and then every 3 months until death
  • Safety Issue?: No

Secondary Measures

• Overall survival as measured by Logrank at 8 weeks after completion of study treatment, and then every 3 months until death
  • Safety Issue?: No
• Progression-free survival as measured by Logrank 8 weeks after completion of study treatment, and then every 3 months until death
  • Safety Issue?: No
• Time to neurological progression as measured by Logrank 8 weeks after completion of study treatment, and then every 3 months until death
  • Safety Issue?: No
• Acute toxicity as measured by EORTC and RTOG scale 8 weeks after completion of study treatment, and then every 3 months until death
  • Safety Issue?: Yes
• Late toxicity as measured by Subjective, Objective, Management and Analytic/Late Effects on Normal Tissues (SOMA/LENT) scale 8 weeks after completion of study treatment, and then every 3 months until death
  • Safety Issue?: Yes
• Quality of life as measured by QLQ-C30 and BN-25 8 weeks after completion of study treatment, and then every 3 months until death
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Diagnosis of brain metastases from a histologically confirmed primary or metastatic extracranial tumor, meeting 1 of the following criteria:
• Stable systemic cancer for the last 3 months (achieved by surgery, radiotherapy, chemotherapy, or hormonal therapy), defined as absence of symptomatic or radiological progression
• Asymptomatic synchronous primary tumor (treatable by surgery, radiotherapy, chemotherapy, or hormonal therapy)
• No metastases outside the CNS
• Unknown primary tumor
• Must have one to three brain lesions, confirmed by enhanced MRI prior to radiosurgery or surgery
• No brain stem metastases
• No leptomeningeal metastases
• No brain metastases from small cell lung cancer, lymphoma, leukemia, myeloma, or germ cell tumors
• Patients planning to undergo radiosurgery must meet the following criteria:
• Largest diameter ≤ 3.5 cm for single metastasis
• Largest diameter ≤ 2.5 cm for multiple metastases
• Stereotactic biopsy required if not extracranial tumor (unknown primary tumor) OR extracranial diagnosis made more than 4 years previously
• Prior neurosurgery patients must have undergone complete surgical resection
• No recurrent brain metastases after prior surgery and/or radiosurgery and/or brain radiotherapy

PATIENT CHARACTERISTICS:

• Age
• 18 and over
• Performance status
• WHO 0-2 (may be assessed under steroid therapy)
• Life expectancy
• Not specified
• Hematopoietic
• Not specified
• Hepatic
• Not specified
• Renal
• Not specified

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• Not specified
• Chemotherapy
• See Disease Characteristics
• No concurrent chemotherapy during whole brain radiotherapy
• Endocrine therapy
• See Disease Characteristics
• Radiotherapy
• See Disease Characteristics
• Surgery
• See Disease Characteristics

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: European Organization for Research and Treatment of Cancer

Overall Clinical Trial Officials and Contacts

Rolf-Peter Mueller, MD  Medizinische Universitaetsklinik I at the University of Cologne  

Information obtained from ClinicalTrials.gov on January 06, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00002899

Study ID Number: CDR0000065229

ClinicalTrials.gov Identifier: NCT00002899

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database