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| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1b: Experimental | Experimental | 600mg alectinib taken orally twice daily |
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| Phase 2: Arm A | Experimental | 600mg alectinib taken orally twice daily |
|
| Phase 2: Arm B | Experimental | Subjects will receive SRS prior to taking alectinib. 24 hours after, but no more than 7 days after last radiation dose, alectinib should be taken at 600mg orally twice daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alectinib | Drug | 600mg taken orally, twice daily for 25 Cycles Cycle = 4 weeks (28 days) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 12 months |
| Phase 1b: Safety and Feasibility | Safety and feasibility will be assessed by frequency of Dose Limiting Toxicities. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 12 months |
| Intracranial disease control rate (icDCR) |
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General Inclusion Criteria:
Subject must meet all of the following applicable inclusion criteria to participate in this study:
Exclusion Criteria:
Subjects meeting any of the criteria below may not participate in the study:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Joshua D Palmer, MD | Contact | 614-293-0871 | joshua.palmer@osumc.edu | |
| Amber Ryba | Contact | 317-634-5842 | 13 | aryba@hoosiercancer.org |
| Name | Affiliation | Role |
|---|---|---|
| Joshua D Palmer, MD | The Ohio State University Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Recruiting | Stanford | California | 94305 | United States |
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| Stereotactic Radiosurgery | Radiation | SRS dose varies by brain met size and location |
|
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icDCR defined as the percentage of patients with a complete response (CR), partial response (PR), or stable disease (SD), per RANO-BM.
| 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. | 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 | 31 months |
| Extracranial PFS | Extracranial PFS will be defined as time from randomization to progression per RECIST v1.1 | 31 months |
| Assess Overall survival (OS) | OS defined as the time from randomization to death from any cause. | 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 | 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. | 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. | 12, 24 months |
| University of Colorado Cancer Center | Recruiting | Aurora | Colorado | 80045 | United States |
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| Ohio State University Comprehensive Cancer Center | Recruiting | Columbus | Ohio | 43210 | United States |
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| ID | Term |
|---|---|
| D008175 | Lung Neoplasms |
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C582670 | alectinib |
| D016634 | Radiosurgery |
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D013238 | Stereotaxic Techniques |
| D019635 | Neurosurgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
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