A Randomised Trial of Surgery Plus Whole Brain Radiotherapy (WBRT) Versus Radiosurgery Plus WBRT for Solitary Brain Metastases
18 Years
N/A
Both
Neoplasm Metastasis, Brain Neoplasm
Trial Information
A Randomised Trial of Surgery Plus Whole Brain Radiotherapy (WBRT) Versus Radiosurgery Plus WBRT for Solitary Brain Metastases
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.
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.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall survival and Quality of life
Outcome Time Frame:
Until death or study completion
Safety Issue:
Yes
Principal Investigator
Daniel Roos, MD, FRANZCR
Investigator Role:
Study Chair
Investigator Affiliation:
Royal Adelaide Hospital
Authority:
Australia: Human Research Ethics Committee
Study ID:
021108
NCT ID:
NCT00124761
Start Date:
December 2002
Completion Date:
May 2009
Related Keywords:
- Neoplasm Metastasis
- Brain Neoplasm
- Radiosurgery
- Brain metastases
- Whole Brain Radiotherapy
- Neurosurgery
- Solitary Brain Metastases
- Adult Tumours Metastatic to Brain
- Brain Neoplasms
- Neoplasms
- Neoplasm Metastasis
- Neoplasms, Second Primary
Name | Location |
|---|
