CMET-48. CE7 CANADIAN CLINICAL TRIALS GROUP /...

CMET-48. CE7 CANADIAN CLINICAL TRIALS GROUP / ALLIANCE FOR CLINICAL TRIALS IN ONCOLOGY. A PHASE III TRIAL OF STEREOTACTIC RADIOSURGERY COMPARED WITH WHOLE BRAIN RADIOTHERAPY (WBRT) FOR 5–15 BRAIN METASTASES

Abstract

BACKGROUND

It is now accepted that for patients with 1–4 brain metastases radiosurgery (SRS) provides improved cognitive and quality of life (QoL) outcomes vs. whole-brain radiotherapy (WBRT). It has been our recent finding that SRS also provides overall survival equivalent to WBRT following resection of a brain metastasis, again with improved cognitive and QoL outcomes. A gap in high-level evidence remains for patients with 5 or more brain metastases. We report on the framework of a Phase III trial.

METHODS

The NCI Brain Malignancies Steering Committee approved the trial concept in March 2017. The trial is to be led by the NCIC and endorsed by the NRG and Alliance for Clinical Trials in Oncology. Planned total accrual is 206 patients randomized to either radiosurgery (volume-based dosing) or WBRT (30Gy in 10 daily fractions) and memantine. Eligible patients will have a maximum total tumor volume of 30cm3. They will have 5–15 parenchymal metastases, free of gross leptomeningeal disease and ECOG performance status 0–2. The primary endpoints will be cognitive deterioration free survival and overall survival. Secondary endpoints include those related to: patient/treatment related outcomes (patterns of failure, validation of a nomogram to predict early appearance of new brain metastases, time to (re-)initiation of systemic therapy, etc.), economic endpoints (comparison based on payer rates (Medicare for US / provincial heath authorities in Canadian jurisdictions with activity-based funding) as well as comparison based on “time based activity costing” in selected institutions), dosimetric endpoints, imaging endpoints and quality of life endpoints. Translational endpoints will include analysis of serum samples to elucidate molecular/genomic mechanisms of neurocognitive decline. Additional translational endpoints are contingent on the outcome of applications for supplemental funding.