This study will consist of a Phase 1b and Phase 2 portion. The Phase 1b portion will enroll first followed by the Phase 2 portion. Each cycle of treatment = 28 days. Subjects will receive alectinib twice daily. Those in the Phase 1b portion will receive alectinib alone. Those in Phase 2 Arm A will receive alectinib alone. Those in Phase 2, Arm B will receive SRS + alectinib. A maximum of 25 cycles (2 years) of alectinib may be administered on study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
56
600mg taken orally, twice daily for 25 Cycles Cycle = 4 weeks (28 days)
SRS dose varies by brain met size and location
Stanford University
Stanford, California, United States
RECRUITINGUniversity of Colorado Cancer Center
Aurora, Colorado, United States
RECRUITINGOhio State University Comprehensive Cancer Center
Columbus, Ohio, United States
RECRUITINGPhase 2: Neurological status and control of CNS disease at 12 months compared to alectinib plus SRS in patients with ≤15 CNS metastases
Neurological status will be measured by a composite endpoint of: -Inntracranial progression(icPD) by RANO-BM criteria or death during the first 12 months. OR -Symptomatic radiation necrosis during the first 12 months. Symptomatic radiation necrosis is defined as requiring initiation of or increased dose of steroids or resulting in seizures or requirement of AEDs or requirement of hospitalization or surgery. OR -Cognitive decline, defined as 1 standard deviation decline from baseline cognitive function during the first 12 months.
Time frame: 12 months
Phase 1b: Safety and Feasibility
Safety and feasibility will be assessed by frequency of Dose Limiting Toxicities.
Time frame: 6 months
Intracranial progression-free survival at 12 months (icPFS12)
icPFS12 is the percentage of patients with icPD at 12 months defined by RANO-BM from randomization or death.
Time frame: 12 months
Intracranial disease control rate (icDCR)
icDCR defined as the percentage of patients with a complete response (CR), partial response (PR), or stable disease (SD), per RANO-BM.
Time frame: 31 months
Intracranial response rate (icRR)
icRR defined as the percentage of patients with a complete response (CR) and partial response (PR), per RANO-BM.
Time frame: 31 months
Intracranial duration of response (icDOR)
icDOR defined as the time when the criteria for CR or PR per RANO-BM were first met to the occurrence of an icPFS event
Time frame: 31 months
Extracranial PFS
Extracranial PFS will be defined as time from randomization to progression per RECIST v1.1
Time frame: 31 months
Assess Overall survival (OS)
OS defined as the time from randomization to death from any cause.
Time frame: 31 months
Safety and Tolerability
Safety and tolerability will be assessed by measuring the frequency and severity of adverse events based on CTCAE v5.0
Time frame: 6 months
Cognitive decline at 12 and 24 months
Rate of cognitive decline, defined as 1 standard deviation decline from baseline cognitive function in at least 1 cognitive test.
Time frame: 12, 24 months
Symptomatic radiation necrosis at 12 and 24 months
Incidence of symptomatic radiation necrosis, defined as requiring initiation of or increased dose of steroids or resulting in seizures or requirement of AEDs or requirement of hospitalization or surgery.
Time frame: 12, 24 months
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