A Trial Comparing Radiosurgery With Surgery for Solitary Brain Metastases

This study has been completed.
Sponsor:
Information provided by:
Royal Adelaide Hospital
ClinicalTrials.gov Identifier:
NCT00124761
First received: July 27, 2005
Last updated: September 2, 2010
Last verified: September 2010
  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: Surgery + WBRT
Radiation: Radiosurgery + WBRT
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised Trial of Surgery Plus Whole Brain Radiotherapy (WBRT) Versus Radiosurgery Plus WBRT for Solitary Brain Metastases

Resource links provided by NLM:


Further study details as provided by Royal Adelaide Hospital:

Primary Outcome Measures:
  • Overall survival and Quality of life [ Time Frame: Until death or study completion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Local and distant recurrence [ Time Frame: Until death or study completion ] [ Designated as safety issue: Yes ]
  • Failure free survival [ Time Frame: Until death or study completion ] [ Designated as safety issue: Yes ]
  • Acute and late toxicities [ Time Frame: Acute toxicities 6 weeks post RT and late toxicities until death ] [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: December 2002
Study Completion Date: May 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: S + WBRT
Experimental: RadioSurgery + Whole Brain Radiotherapy Radiation: Radiosurgery + WBRT
Radiosurgery - Marginal dose based on maximum tumour diameter
Other Name: RS + WBRT

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.

  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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Sponsors and Collaborators
Royal Adelaide Hospital
Investigators
Study Chair: Daniel Roos, MD, FRANZCR Royal Adelaide Hospital
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: A/Prof Daniel Roos, Royal Adelaide Hospital
ClinicalTrials.gov Identifier: NCT00124761     History of Changes
Other Study ID Numbers: 021108
Study First Received: July 27, 2005
Last Updated: September 2, 2010
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

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplastic Processes
Pathologic Processes

ClinicalTrials.gov processed this record on August 20, 2014