Vorinostat is a potent and well tolerated HDAC inhibitor. It has been reported to enhance radiosensitivity of cancer cells. We hypothesize that the addition of vorinostat to WBRT may increase therapeutic efficacy for patients with brain metastases.
Whole brain radiotherapy (WBRT) is the treatment of choice for the majority of patients with brain metastases. Although WBRT yields high radiologic response rate (27\~56%) and is effective in palliation of neurologic symptoms, the response duration is limited and neurologic progression remains the main cause of death in a significant number of patients. Vorinostat is reasonably well tolerated and there is also compelling evidence that vorinostat may serve as a radiosensitizer. Preclinical studies of HDAC inhibition have also shown efficacy in neuron protection. These data suggest that the addition of vorinostat to the standard therapy of WBRT may potentially increase their therapeutic efficacy without increasing neurotoxicity, and support the rationale of this phase II trial of vorinostat with WBRT in patients with brain metastases.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
4
Run-in phase: WBRT: 2.5 Gy per fraction per day, day 1 through day 5 every week for 15 days, to a total dose of 37.5Gy. Vorinostat: 400 mg/day during WBRT, day 1 through day 7 every week till one day after WBRT. Randomization phase: WBRT: 2.5 Gy per fraction per day, day 1 through day 5 every week for 15 days, to a total dose of 37.5Gy. Vorinostat or placebo: 400 or 300 mg/day during radiation therapy (based on the results of run-in phase), day 1 through day 7 every week till one day after WBRT.
Randomization phase: WBRT: 2.5 Gy per fraction per day, day 1 through day 5 every week for 15 days, to a total dose of 37.5Gy. Vorinostat or placebo: 400 or 300 mg/day during radiation therapy (based on the results of run-in phase), day 1 through day 7 every week till one day after WBRT.
National Taiwan University Hospital
Taipei, Taiwan
To evaluate brain-specific progression free survival rate at 6 months
Time frame: 6 months
brain-specific PFS
Time frame: from randomization to progression of brain metastasis or death, assessed up to 36 months
PFS
Time frame: from randomization to progression or death, assessed up to 36 months
response rate
Time frame: 6 months
time to neuro-cognitive progression
Time frame: 12 months
time to neurologic progression
Time frame: 12 months
HRQoL
Time frame: 12 months
Overall survival
Time frame: from randomization to death, assessed up to 36 months
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