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.
Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18 years at the time of consent.
Fluent English skills with comprehensive/speaking skills equal to those of a native English speaker as assessed by the site investigator.
ECOG Performance Status of ≤ 2 within 14 days prior to registration.
Active infection requiring systemic therapy.
Malabsorption syndrome or other condition that would interfere with enteral absorption
Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial.
Parallel
Alectinib
Drug600mg taken orally, twice daily for 25 Cycles Cycle = 4 weeks (28 days)
Stereotactic Radiosurgery
RadiationSRS dose varies by brain met size and location
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.
Phase 1b: Safety and Feasibility
Safety and feasibility will be assessed by frequency of Dose Limiting Toxicities.
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.
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.
Intracranial response rate (icRR)
icRR defined as the percentage of patients with a complete response (CR) and partial response (PR), per RANO-BM.
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
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Joshua Palmer
Lead sponsor
Hoosier Cancer Research Network
Sponsor institution
Genentech, Inc.
Collaborator
