Adjuvant Radiation Therapy in Treating Patients With Brain Metastases

Metastatic Cancer Clinical Trial

Official title:

Phase III Trial on Convergent Beam Irradiation of Cerebral Metastases

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00002899
• Other study ID #: EORTC-22952-26001
• Secondary ID: EORTC-22952EORTC
• Status: Terminated
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: June 29, 2012
• Start date: November 1996

Study information

• Verified date: June 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 340
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Procedure:
• adjuvant therapy

Radiation:
• radiation therapy

• stereotactic radiosurgery

Locations

Country	Name	City	State
Belgium	Academisch Ziekenhuis der Vrije Universiteit Brussel	Brussels
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	Algemeen Ziekenhuis Sint-Augustinus	Wilrijk
Finland	Helsinki University Central Hospital	Helsinki
France	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz	Besancon
France	Centre Hospitalier Regional et Universitaire de Lille	Lille
France	Centre Leon Berard	Lyon
France	Centre Antoine Lacassagne	Nice
France	Centre Haute Energie	Nice
France	CHU Pitie-Salpetriere	Paris
France	Centre Eugene Marquis	Rennes
Germany	Medizinische Universitaetsklinik I at the University of Cologne	Cologne
Germany	Medizinische Klinik und Poliklinik III - Universitaetsklinikum Leipzig	Leipzig
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Germany	Heinrich-Braun-Krankenhaus Zwickau	Zwickau
Israel	Rambam Medical Center	Haifa
Italy	Ospedale Niguarda Ca'Granda	Milan
Italy	Istituto Nazionale Neurologico Carlo Besta	Milano
Italy	Azienda Sanitaria Ospedaliera Ordine Mauriziano	Torino
Italy	Ospedale Ostetrico Ginecologica Sant Anna	Torino
Italy	Universita Degli Studi di Turin	Torino
Latvia	Paula Stradina Kliniskas Universitates Slimnica	Riga
Netherlands	Maastro Clinic - Locatie Maastricht	Maastricht
Portugal	Hospital Santa Maria	Lisbon
Spain	Institut Catala d'Oncologia - Hospital Duran i Reynals	Barcelona
Switzerland	Oncology Institute of Southern Switzerland	Bellinzona
Turkey	Marmara University Hospital	Istanbul
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland
United Kingdom	University College Hospital - London	London	England
United Kingdom	Nottingham City Hospital NHS Trust	Nottingham	England
United Kingdom	Royal Preston Hospital	Preston	England
United Kingdom	Royal Marsden NHS Foundation Trust - Surrey	Sutton	England
United Kingdom	Southend University Hospital NHS Foundation Trust	Westcliff-On-Sea	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  Finland,  France,  Germany,  Israel,  Italy,  Latvia,  Netherlands,  Portugal,  Spain,  Switzerland,  Turkey,  United Kingdom, 

References & Publications (3)

Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG, Fariselli L, Tzuk-Shina T, Kortmann RD, Carrie C, Ben Hassel M, Kouri M, Valeinis E, van den Berge D, Collette S, Collette L, Mueller RP. Adjuvant whole-brain radiotherapy versus observat — View Citation

Mekhail T, Sombeck M, Sollaccio R. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. Curr Oncol Rep. 2011 Aug;13(4):255-8. doi: 10.100 — View Citation

Mueller RP, Soffietti R, Abacioglu MU, et al.: Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of 1-3 cerebral metastases: results of the EORTC 22952-26001 study. [Abstract] J Clin Oncol 27 (Suppl 15): A-2008,

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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			No
Secondary	Overall survival as measured by Logrank at 8 weeks after completion of study treatment, and then every 3 months until death			No
Secondary	Progression-free survival as measured by Logrank 8 weeks after completion of study treatment, and then every 3 months until death			No
Secondary	Time to neurological progression as measured by Logrank 8 weeks after completion of study treatment, and then every 3 months until death			No
Secondary	Acute toxicity as measured by EORTC and RTOG scale 8 weeks after completion of study treatment, and then every 3 months until death			Yes
Secondary	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			Yes
Secondary	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			No