A Trial Comparing Radiosurgery With Surgery for Solitary Brain Metastases

September 2, 2010 updated by: Royal Adelaide Hospital

A Randomised Trial of Surgery Plus Whole Brain Radiotherapy (WBRT) Versus Radiosurgery Plus WBRT for Solitary Brain Metastases

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.
  • 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.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Surgery + Whole Brain Radiotherapy
Procedure: Surgery + WBRT
Surgery - complete excision of Solitary Brain Metastasis with 30 Gy in 10 fractions over 2 2 1/2 weeks
Other Names:
  • S + WBRT
EXPERIMENTAL: RadioSurgery + Whole Brain Radiotherapy
Radiation: Radiosurgery + WBRT
Radiosurgery - Marginal dose based on maximum tumour diameter
Other Names:
  • RS + WBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival and Quality of life
Time Frame: Until death or study completion
Until death or study completion

Secondary Outcome Measures

Outcome Measure
Time Frame
Local and distant recurrence
Time Frame: Until death or study completion
Until death or study completion
Failure free survival
Time Frame: Until death or study completion
Until death or study completion
Acute and late toxicities
Time Frame: Acute toxicities 6 weeks post RT and late toxicities until death
Acute toxicities 6 weeks post RT and late toxicities until death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Royal Adelaide Hospital

Investigators

  • Study Chair: Daniel Roos, MD, FRANZCR, Royal Adelaide Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2002

Primary Completion (ACTUAL)

April 1, 2009

Study Completion (ACTUAL)

May 1, 2009

Study Registration Dates

First Submitted

July 27, 2005

First Submitted That Met QC Criteria

July 27, 2005

First Posted (ESTIMATE)

July 28, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

September 6, 2010

Last Update Submitted That Met QC Criteria

September 2, 2010

Last Verified

September 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 021108

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Neoplasm Metastasis

Clinical Trials on Surgery + WBRT

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Slovakia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe