Phase II Study of Gamma Knife Radiosurgery and Temozolomide (Temodar) for Newly Diagnosed Brain Metastases
This is a phase II study. The primary endpoint is the proportion of patients with newly
developed metastases who develop new brain metastases within the first year of undergoing
stereotactic radiation combined with the administration of temozolamide within the first
year post treatment. Retrospective and prospective studies suggest that 50- 60% of
long-term survivors develop new brain metastases. Since it is important to observe all
patients recruited for a minimum of a year to measure the primary outcome, traditional phase
2 designs such as Simon's two stage optimal design or the mini-max design are not practical
in this case. Survival and QOL are secondary end points. QOL will be measured using the
Functional Assessment of Cancer Therapy (FACT -BR). It will be administered at baseline, at
week four and every three months for 24 months.
This protocol includes radiosurgery with standard radiation doses (15-24 Gy based upon RTOG
9005). Patient may be registered after radiosurgery as long as Temodar is started within
two weeks of radiosurgery.
Beginning within two weeks after radiosurgery: TMZ 200mg/m2 days 1-5 repeat q28 days.
Patients who have received prior chemotherapy will receive 150 mg/m2 days 1-5.
Temozolomide is continued until there is disease progression defined by systemic progression
or new metastases. If lesion treated with radiosurgery progresses in the absence of new CNS
tumors or systemic progression, then TMZ will continue. Temozolomide is discontinued for
systemic progression requiring other systemic chemotherapy.
Palliative radiation may be administered to non-CNS sites during protocol treatment, but
additional systemic chemotherapy will not be administered until patients progress
systemically or until new metastases develop.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the efficacy of temozolomide in preventing the development of new brain metastases within the first year in patients undergoing stereotactic radiation for newly diagnosed brain metastases
John Fiveash, M.D.
University of Alabama at Birmingham
United States: Institutional Review Board
|University of Alabama at Birmingham||Birmingham, Alabama 35294-3300|