Clinical trial NCT00002899: Adjuvant Radiation Therapy in Treating Patients With Brain Metastases
Official title: Phase III Trial on Convergent Beam Irradiation of Cerebral Metastases
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Metastatic Cancer
Keywords: tumors metastatic to brain
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 340
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: 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 outcomes:
measure: Overall survival as measured by Logrank at 8 weeks after completion of study treatment, and then every 3 months until death
measure: Progression-free survival as measured by Logrank 8 weeks after completion of study treatment, and then every 3 months until death
measure: Time to neurological progression as measured by Logrank 8 weeks after completion of study treatment, and then every 3 months until death
measure: Acute toxicity as measured by EORTC and RTOG scale 8 weeks after completion of study treatment, and then every 3 months until death
measure: 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
measure: 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
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Academisch Ziekenhuis der Vrije Universiteit Brussel
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Wilrijk
country: Belgium
facility: Algemeen Ziekenhuis Sint-Augustinus
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Besancon
country: France
facility: Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
city: Lille
country: France
facility: Centre Hospitalier Regional et Universitaire de Lille
city: Lyon
country: France
facility: Centre Leon Berard
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nice
country: France
facility: Centre Haute Energie
city: Paris
country: France
facility: CHU Pitie-Salpetriere
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Cologne
country: Germany
facility: Medizinische Universitaetsklinik I at the University of Cologne
city: Leipzig
country: Germany
facility: Medizinische Klinik und Poliklinik III - Universitaetsklinikum Leipzig
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Zwickau
country: Germany
facility: Heinrich-Braun-Krankenhaus Zwickau
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Milano
country: Italy
facility: Istituto Nazionale Neurologico Carlo Besta
city: Milan
country: Italy
facility: Ospedale Niguarda Ca'Granda
city: Torino
country: Italy
facility: Ospedale Ostetrico Ginecologica Sant Anna
city: Torino
country: Italy
facility: Universita Degli Studi di Turin
city: Torino
country: Italy
facility: Azienda Sanitaria Ospedaliera Ordine Mauriziano
city: Riga
country: Latvia
facility: Paula Stradina Kliniskas Universitates Slimnica
city: Maastricht
country: Netherlands
facility: Maastro Clinic - Locatie Maastricht
city: Lisbon
country: Portugal
facility: Hospital Santa Maria
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia - Hospital Duran i Reynals
city: Bellinzona
country: Switzerland
facility: Oncology Institute of Southern Switzerland
city: Istanbul
country: Turkey
facility: Marmara University Hospital
city: London
country: United Kingdom
facility: University College Hospital - London
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - Surrey
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
Study officials:
affiliation: Medizinische Universitaetsklinik I at the University of Cologne
name: Rolf-Peter Mueller, MD
role: STUDY_CHAIR
affiliation: Universita Degli Studi di Turin
name: Riccardo Soffietti, MD
role: STUDY_CHAIR
References:
citation: Kocher M, Soffietti R, Abacioglu U, Villa 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 observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol. 2011 Jan 10;29(2):134-41. doi: 10.1200/JCO.2010.30.1655. Epub 2010 Nov 1.
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: 10.1007/s11912-011-0180-1. No abstract available.
citation: Churilla TM, Chowdhury IH, Handorf E, Collette L, Collette S, Dong Y, Alexander BM, Kocher M, Soffietti R, Claus EB, Weiss SE. Comparison of Local Control of Brain Metastases With Stereotactic Radiosurgery vs Surgical Resection: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2019 Feb 1;5(2):243-247. doi: 10.1001/jamaoncol.2018.4610.
citation: Churilla TM, Handorf E, Collette S, Collette L, Dong Y, Aizer AA, Kocher M, Soffietti R, Alexander BM, Weiss SE. Whole brain radiotherapy after stereotactic radiosurgery or surgical resection among patients with one to three brain metastases and favorable prognoses: a secondary analysis of EORTC 22952-26001. Ann Oncol. 2017 Oct 1;28(10):2588-2594. doi: 10.1093/annonc/mdx332.
citation: Soffietti R, Kocher M, Abacioglu UM, Villa 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, Mueller RP, Tridello G, Collette L, Bottomley A. A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol. 2013 Jan 1;31(1):65-72. doi: 10.1200/JCO.2011.41.0639. Epub 2012 Dec 3.