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Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over Other 021108 NCT00124761

Trial Description

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 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.

Further Study Information

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 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.

Trial Contact Information

Trial Lead Organizations/Sponsors

Royal Adelaide Hospital Cancer Centre

Daniel Roos, FRANZCR

Study Chair

Daniel Roos, FRANZCR

Ph: +61 8 8222 4000

Australia
South Australia
	Adelaide
	Royal Adelaide Hospital Cancer Centre
		Daniel Roos, FRANZCR	Ph: +61 8 8222 4000
		Daniel Roos, FRANZCR	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00124761
Information obtained from ClinicalTrials.gov on May 27, 2008