Phase I/II Trial to Determine the Neurocognitive Decline in Patients With Multiple (>6) Brain Metastases Treated With Distributed Stereotactic Radiosurgery
Description:
On review of our experience with treatment for brain metastases since 2009, we have treated
over 100 patients with 6 or more metastases in a single radiosurgery session. In the past
year and a half (2015-16) there have been approximately 50 patients treated with six or more
metastases, indicating that there has been a shift in management of intracranial metastatic
disease with increasing preference for radiosurgery despite the presences of greater
metastatic burden. The phase I component will accrue 7-15 patients at each dose cohort until
the MTD is determined. Once the MTD is reached, the phase II component will commence with a
total of 50 patients total enrolled at the MTD, with a study time of 3 years. The primary
endpoint of the phase I component is toxicity. The primary endpoint of the phase II component
is the change in neurocognitive function, defined by a decline in the Hopkins Verbal Learning
Test- Revised delayed recall. Data from the WBRT-alone arm of the PCI-P-120-9801 phase III
trial evaluating WBRT plus motexafin gadolinium demonstrated a 30% mean relative decline in
the HVLT-R delayed recall score from baseline to 4 months, with a standard deviation of 41%
9,10. More recently, in patients treated with SRS alone for 1-3 metastases versus SRS plus
whole brain radiotherapy, the 4-month rates of HVLT-R delayed recall deterioration were 6%
and 22% for the SRS alone arm and SRS + whole brain radiotherapy arm, respectively. Given the
greater intracranial burden of disease, we estimate the mean relative decline in HVLT-R
delayed recall to be intermediate between SRS alone for 1-3 metastases and whole brain
radiotherapy. We predict that after SRS for multiple metastases the mean relative decline in
delayed recall as 15%, an improvement over the historical control of whole brain radiotherapy
alone which had a mean relative decline in HVLT-R delayed recall of 30%.
Condition:
Brain Metastases
Treatment:
Stereotactic Radiosurgery
Start Date:
December 5, 2017
Sponsor:
University of Texas Southwestern Medical Center
For More Information:
https://clinicaltrials.gov/show/NCT03508752