Adjuvant Radiation Therapy in Treating Patients With Brain Metastases

Condition(s) targeted: Brain and Central Nervous System Tumors

Intervention: adjuvant therapy (Procedure); radiation therapy (Procedure); stereotactic radiosurgery (Procedure)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: European Organization for Research and Treatment of Cancer

Official(s) and/or principal investigator(s):
Rolf-Peter Mueller, MD, Affiliation: Medizinische Universitaetsklinik I at the University of Cologne
Riccardo Soffietti, MD, Affiliation: Universita Degli Studi di Turin

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.

Official title: Phase III Trial on Convergent Beam Irradiation of Cerebral Metastases

Study design: Treatment, Randomized, Active Control

Primary outcome: 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

Secondary outcome:

Overall survival as measured by Logrank at 8 weeks after completion of study treatment, and then every 3 months until death

Progression-free survival as measured by Logrank 8 weeks after completion of study treatment, and then every 3 months until death

Time to neurological progression as measured by Logrank 8 weeks after completion of study treatment, and then every 3 months until death

Acute toxicity as measured by EORTC and RTOG scale 8 weeks after completion of study treatment, and then every 3 months until death

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

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

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Academisch Ziekenhuis der Vrije Universiteit Brussel, Brussels 1090, Belgium

Algemeen Ziekenhuis Sint-Augustinus, Wilrijk 2610, Belgium

U.Z. Gasthuisberg, Leuven B-3000, Belgium

Helsinki University Central Hospital, Helsinki FIN-00029, Finland

Centre Antoine Lacassagne, Nice 06189, France

Centre Eugene Marquis, Rennes 35042, France

Centre Haute Energie, Nice 6000, France

Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz, Besancon 25030, France

Centre Hospitalier Regional et Universitaire de Lille, Lille 59037, France

Centre Leon Berard, Lyon 69008, France

CHU Pitie-Salpetriere, Paris 75651, France

Heinrich-Braun-Krankenhaus Zwickau, Zwickau 08060, Germany

Medizinische Klinik und Poliklinik III - Universitaetsklinikum Leipzig, Leipzig D-04103, Germany

Medizinische Universitaetsklinik I at the University of Cologne, Cologne D-50924, Germany

Universitaetsklinikum Tuebingen, Tuebingen D-72076, Germany

Rambam Medical Center, Haifa 31096, Israel

Azienda Sanitaria Ospedaliera Ordine Mauriziano, Torino 10128, Italy

Istituto Nazionale Neurologico Carlo Besta, Milano 20133, Italy

Ospedale Niguarda Ca'Granda, Milan 20162, Italy

Ospedale Ostetrico Ginecologica Sant Anna, Torino 10126, Italy

Universita Degli Studi di Turin, Torino 10126, Italy

Paula Stradina Kliniskas Universitates Slimnica, Riga 1002, Latvia

Maastro Clinic - Locatie Maastricht, Maastricht NL-6229 ET, Netherlands

Hospital Santa Maria, Lisbon 1699, Portugal

Institut Catala d'Oncologia - Hospital Duran i Reynals, Barcelona 08907, Spain

Oncology Institute of Southern Switzerland, Bellinzona CH-6500, Switzerland

Marmara University Hospital, Istanbul 81190, Turkey

Nottingham City Hospital NHS Trust, Nottingham, England NG5 1PB, United Kingdom

Royal Marsden NHS Foundation Trust - Surrey, Sutton, England SM2 5PT, United Kingdom

Royal Preston Hospital, Preston, England PR2 9HT, United Kingdom

Southend University Hospital NHS Foundation Trust, Westcliff-On-Sea, England SS0 0RY, United Kingdom

University College Hospital - London, London, England WC1E 6AU, United Kingdom

Edinburgh Cancer Centre at Western General Hospital, Edinburgh, Scotland EH4 2XU, United Kingdom

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

Starting date: November 1996
Last updated: December 25, 2007