DURABLE: Delayed or Upfront Brain RAdiotherapy in Treatment naïve Lung Cancer Patients With Asymptomatic or Minimally Symptomatic Brain Metastases and rEarrangements
Summary
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.
Arms & interventions
- DrugAlectinib
600mg taken orally, twice daily for 25 Cycles Cycle = 4 weeks (28 days)
- RadiationStereotactic Radiosurgery
SRS dose varies by brain met size and location
Outcome measures
Primary
Phase 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
Secondary
Intracranial progression-free survival at 12 months (icPFS12)
Time frame: 12 months
Intracranial disease control rate (icDCR)
Time frame: 31 months
Intracranial response rate (icRR)
Time frame: 31 months
Intracranial duration of response (icDOR)
Time frame: 31 months
Extracranial PFS
Time frame: 31 months
Assess Overall survival (OS)
Time frame: 31 months
Safety and Tolerability
Time frame: 6 months
Cognitive decline at 12 and 24 months
Time frame: 12, 24 months
Symptomatic radiation necrosis at 12 and 24 months
Time frame: 12, 24 months
Eligibility criteria
Study locations (3)
Stanford University
Stanford, California, 94305
University of Colorado Cancer Center
Aurora, Colorado, 80045
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210