A Trial Comparing Radiosurgery With Surgery for Solitary Brain Metastases - Full Text View

Sponsored by:	Royal Adelaide Hospital
Information provided by:	Royal Adelaide Hospital
ClinicalTrials.gov Identifier:	NCT00124761

Purpose

This study examines surgery versus radiosurgery (highly focussed radiation) for the treatment of cancer which has spread to one spot in the brain (solitary brain “metastasis”). For these two treatment options, it will compare patients’ survival times, quality of life, control rate of the brain metastases and side effects. It uses the most rigorous scientific method available called “randomisation” which minimises biases that exist with other types of studies. It will involve 30 – 40 patients.

Condition	Intervention	Phase
Neoplasm Metastasis Brain Neoplasm	Procedure: Radiosurgery (compared with surgery)	Phase III

MedlinePlus related topics: Brain Cancer Cancer

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Randomised Trial of Surgery Plus Whole Brain Radiotherapy (WBRT) Versus Radiosurgery Plus WBRT for Solitary Brain Metastases

Further study details as provided by Royal Adelaide Hospital:

Primary Outcome Measures:

Overall survival
Quality of life

Secondary Outcome Measures:

Local and distant recurrence
Failure free survival
Acute and late toxicities

Estimated Enrollment:	40
Study Start Date:	December 2002

Detailed Description:

Primary objectives – to evaluate for solitary brain metastases whether both overall survival and health related quality of life (HQoL) in patients treated with radiosurgery (RS) plus whole brain radiotherapy (WBRT) are non-inferior to those of patients treated with surgery (S) plus WBRT.

Secondary objectives – to compare between the two treatment arms time to local and distant brain recurrence, failure free survival, acute and late toxicity.

Hypothesis – Patients treated with RS + WBRT have neither worse survival nor worse quality of life than those treated with S + WBRT.

Research plan:

Trial design – Single-centre prospective randomised Phase III controlled two arm non-inferiority study with the “gold standard” of surgery (plus WBRT) as the control arm. Blinding to trial arm will not be feasible. Stratification is by Radiation Therapy Oncology Group Recursive Partitioning Analysis (RPA) prognostic Class 1 vs 2 vs 3 and by Centre.
Main eligibility criteria - single presumed metastasis on MRI brain; systemic cancer diagnosed within the last 5 years; considered suitable for both S and RS; written informed consent.
Main exclusion criteria - surgery indicated for life-threatening raised intra-cranial pressure or tissue diagnosis; surgery contra-indicated by site or medical co-morbidities; leptomeningeal disease; primary is small cell lung cancer, germ cell tumour, lymphoma, leukaemia or myeloma.
Radiation – WBRT dose is 30 Gy in 10 fractions over 2 weeks. RS dose is based on lesion size up to 4 cm (15-20 Gy).
Surgery – Aim is complete excision.
Treatment sequence and patient assessments – Any sequencing of S/RS and WBRT is allowable, as long as the brain treatment is commenced within 2 weeks after, and completed within 6½ weeks after the diagnostic MRI brain. Assessments at baseline, during brain treatment, at 2 and 3 months after commencement, then 3 monthly, with MRI brain at 3 and 6 months, and/or as clinically indicated. Acute toxicity monitored by NCI Common Toxicity Criteria, late toxicity by RTOG/EORTC Late Radiation Morbidity Scheme. HQoL assessed by EORTC QLQ-C30 and QLQ-BN20.
Sample size – 30-40 patients over 5 years.

Outcomes and Significance:

The trial will enable Level I evidence to be applied to this common clinical problem. Patients will be able to make an informed choice based upon valid survival, quality of life and toxicity comparisons.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Single presumed brain metastasis on contrast magnetic resonance imaging (MRI) scan within two weeks before commencement of treatment.
Systemic cancer diagnosed histologically or cytologically synchronous with, or within 5 years of treatment of the presumed brain metastasis (other than non-melanoma skin cancer and cancer in-situ of the cervix, neither of which would be reasonably attributable as the primary site). Exception - melanoma diagnosed > 5 years previously is allowable in view of the extremely variable natural history of melanoma.
Age >= 18 (no upper age limit).
Considered suitable for both S and RS by the neurosurgeon and radiation oncologist (see exclusions).
Patient must agree to adjuvant WBRT.
RTOG RPA Class 1 or 2 (Karnofsky Performance Status [KPS] >= 70 after adequate trial of corticosteroids).
RPA Class 3 patients (KPS < 70) eligible if it is considered that the poor performance status is due primarily to the solitary metastasis, aggressive local treatment of which may be expected to restore good performance status. This would ordinarily be associated with minimal systemic disease burden.
Accessible for treatment and follow-up.
Patient is infertile or is aware of the risk of becoming pregnant or fathering children and will use adequate contraception.
Written informed consent

Exclusion:

Previous history of brain metastasis(es)
Surgery indicated to relieve life-threatening raised intracranial pressure or excision required for tissue diagnosis (no extra-cranial site to biopsy ie unknown primary). However, prior diagnostic (non-excisional) biopsy is allowable – it is acknowledged that the 50% probability of a repeat surgical procedure on subsequent randomisation would not be acceptable to many patients and clinicians.
Surgery contraindicated by site (e.g. thalamus, brain stem) or medical co-morbidities.
Leptomeningeal disease.
Primary is small cell lung cancer, germ cell tumour, lymphoma, leukaemia or myeloma.
Prior cranial RT (including RS).
Patient is pregnant.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00124761

Contacts

Contact: Daniel Roos, FRANZCR

+61 8 8222 4000

Locations

Australia, South Australia
Royal Adelaide Hospital	Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Daniel Roos, FRANZCR +61 8 8222 4000
Principal Investigator: Daniel Roos, FRANZCR

Sponsors and Collaborators

Royal Adelaide Hospital

Investigators

Study Chair:

Daniel Roos, FRANZCR

Royal Adelaide Hospital

More Information

Publications:

Roos DE, Brophy BP, Zavgorodni SF, Katsilis ES. Radiosurgery for brain metastases at the Royal Adelaide Hospital: are we treating the right patients? Australas Radiol. 2002 Dec;46(4):402-8.

Study ID Numbers:	021108
Study First Received:	July 27, 2005
Last Updated:	February 10, 2006
ClinicalTrials.gov Identifier:	NCT00124761
Health Authority:	Australia: Human Research Ethics Committee

Keywords provided by Royal Adelaide Hospital:

Radiosurgery
Brain metastases
Whole Brain Radiotherapy

Neurosurgery
Solitary Brain Metastases
Adult Tumours Metastatic to Brain

Study placed in the following topic categories:

Brain Neoplasms
Neoplasm Metastasis
Central Nervous System Diseases

Central Nervous System Neoplasms
Brain Diseases
Nervous System Neoplasms

Additional relevant MeSH terms:

Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms by Site
Nervous System Diseases

ClinicalTrials.gov processed this record on January 16, 2009