Neoplasm MetastasisPhase 3NCT00124761
A Trial Comparing Radiosurgery With Surgery for Solitary Brain Metastases
A Phase 3 study testing Surgery + WBRT and Radiosurgery + WBRT in people with Neoplasm Metastasis and Brain Neoplasm, run by Royal Adelaide Hospital at 1 site in Australia.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasm Metastasis, Brain Neoplasm
- What is being tested?
- Surgery + WBRT and Radiosurgery + WBRT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteAustralia
- Study dates
- Dec 2002to May 2009
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Show all 10Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Neoplasm Metastasis, Brain Neoplasm
- Being tested
- Surgery + WBRT, Radiosurgery + WBRT
- Keywords
- Radiosurgery, Brain metastases, Whole Brain Radiotherapy, Neurosurgery, Solitary Brain Metastases, Adult Tumours Metastatic to Brain
- Medical subject headings
- Neoplasm Metastasis, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgery + WBRTProcedure or surgery
Also called S + WBRT
Surgery - complete excision of Solitary Brain Metastasis with 30 Gy in 10 fractions over 2 2 1/2 weeks
Radiosurgery + WBRTRadiation
Also called RS + WBRT
Radiosurgery - Marginal dose based on maximum tumour diameter
| Study group | Role | What they receive |
|---|---|---|
| Surgery + Whole Brain Radiotherapy | Other | Not described Receives: Procedure: Surgery + WBRT |
| RadioSurgery + Whole Brain Radiotherapy | Experimental | Not described Receives: Radiation: Radiosurgery + WBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival and Quality of life
Measured: Until death or study completion
Secondary outcomes (3)
Local and distant recurrence
Measured: Until death or study completion
Failure free survival
Measured: Until death or study completion
Acute and late toxicities
Measured: Acute toxicities 6 weeks post RT and late toxicities until death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2005 (estimated)
- Study startDec 2002
- Primary completionApr 2009
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neoplasm MetastasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Adelaide Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Daniel Roos, MD, FRANZCR, Study chair, Royal Adelaide Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00124761
- Sponsor's protocol ID
- 021108
- Status last verified
- Sep 2010
- First submitted
- 27 Jul 2005
- Last updated
- 6 Sep 2010
- Results posted
- No
- Data monitoring committee
- No
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. doi: 10.1046/j.1440-1673.2002.t01-1-01094.x.
PubMed 12452912Roos DE, Smith JG, Stephens SW. Radiosurgery versus surgery, both with adjuvant whole brain radiotherapy, for solitary brain metastases: a randomised controlled trial. Clin Oncol (R Coll Radiol). 2011 Nov;23(9):646-51. doi: 10.1016/j.clon.2011.04.009. Epub 2011 May 17.
PubMed 21592754
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Trial of Surgery Plus Whole Brain Radiotherapy (WBRT) Versus Radiosurgery Plus WBRT for Solitary Brain Metastases
- ClinicalTrials.gov ID
- NCT00124761
- Acronym / sponsor ID
- 021108
- Conditions
- Neoplasm Metastasis, Brain Neoplasm
- Keywords
- Radiosurgery, Brain metastases, Whole Brain Radiotherapy, Neurosurgery, Solitary Brain Metastases, Adult Tumours Metastatic to Brain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Royal Adelaide HospitalUniversity, hospital or other
- Study start
- Dec 2002
- Primary completion
- Apr 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 28 Jul 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Surgery + Whole Brain Radiotherapy | Other | Procedure: Surgery + WBRT |
| RadioSurgery + Whole Brain Radiotherapy | Experimental | Radiation: Radiosurgery + WBRT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Surgery + WBRTAlso: S + WBRTSurgery - complete excision of Solitary Brain Metastasis with 30 Gy in 10 fractions over 2 2 1/2 weeks | Procedure or surgery | Surgery + Whole Brain Radiotherapy |
| Radiosurgery + WBRTAlso: RS + WBRTRadiosurgery - Marginal dose based on maximum tumour diameter | Radiation | RadioSurgery + Whole Brain Radiotherapy |
Primary outcome
Overall survival and Quality of life
Time frame: Until death or study completion
3 secondary outcomes
Local and distant recurrence
Time frame: Until death or study completion
Failure free survival
Time frame: Until death or study completion
Acute and late toxicities
Time frame: Acute toxicities 6 weeks post RT and late toxicities until death
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2010.
- Background: PubMed 12452912Roos 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. doi: 10.1046/j.1440-1673.2002.t01-1-01094.x.
- Derived from this study: PubMed 21592754Roos DE, Smith JG, Stephens SW. Radiosurgery versus surgery, both with adjuvant whole brain radiotherapy, for solitary brain metastases: a randomised controlled trial. Clin Oncol (R Coll Radiol). 2011 Nov;23(9):646-51. doi: 10.1016/j.clon.2011.04.009. Epub 2011 May 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Roos, MD, FRANZCR study chair
Royal Adelaide Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Surgery + WBRT and Radiosurgery + WBRT in people with Neoplasm Metastasis and Brain Neoplasm, run by Royal Adelaide Hospital at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival and Quality of life (time frame: Until death or study completion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00124761, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2010.