Genetic Testing in Guiding Treatment for Patients With Brain Metastases
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ClinicalTrials.gov Identifier: NCT03994796 |
Recruitment Status :
Recruiting
First Posted : June 21, 2019
Last Update Posted : June 7, 2022
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Tracking Information | |||||
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First Submitted Date ICMJE | June 14, 2019 | ||||
First Posted Date ICMJE | June 21, 2019 | ||||
Last Update Posted Date | June 7, 2022 | ||||
Actual Study Start Date ICMJE | August 15, 2019 | ||||
Estimated Primary Completion Date | October 2024 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Objective response rate in the brain [ Time Frame: Up to 5 years ] Assessed per Response Assessment in Neuro-Oncology (RANO) criteria for brain metastases. The response rate is defined as the number of patients who have achieved complete response (CR) or partial response (PR) per RANO for brain metastases criteria during treatment with CDK, PI3K, or NTRK/ROS inhibitors divided by total number of evaluable patients. The response rate and associated exact confidence interval will be estimated within each cohort defined by the targeted agent and histology.
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Genetic Testing in Guiding Treatment for Patients With Brain Metastases | ||||
Official Title ICMJE | Genomically-Guided Treatment Trial in Brain Metastases | ||||
Brief Summary | This phase II trial studies how well genetic testing works in guiding treatment for patients with solid tumors that have spread to the brain. Several genes have been found to be altered or mutated in brain metastases such as NTRK, ROS1, CDK or PI3K. Medications that target these genes such as abemaciclib, paxalisib, and entrectinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Genetic testing may help doctors tailor treatment for each mutation. | ||||
Detailed Description | PRIMARY OBJECTIVES: I. To determine the activity of a CDK inhibitor in patients with progressive brain metastases derived from lung cancer, breast cancer, and other cancers harboring actionable genetic alterations associated with sensitivity to CDK inhibitors as measured by response rate (Response Assessment in Neuro-Oncology [RANO] criteria). II. To determine the activity of a PI3K inhibitor in patients with progressive brain metastases derived from lung cancer, breast cancer, and other cancers harboring actionable genetic alterations in the PI3K pathway as measured by response rate (RANO criteria). III: To determine the activity of an NTRK/ROS1 inhibitor in patients with progressive brain metastases derived from lung cancer harboring actionable NTRK/ROS1 gene fusions as measured by response rate (RANO criteria). SECONDARY OBJECTIVES: I. To evaluate the systemic response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria in each of the cohorts determined by treatment and primary cancer type. II. To evaluate the clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD]) by Brain Metastases (BM)-RANO for central nervous system (CNS) in each of the cohorts determined by treatment and primary cancer type. III. To evaluate the clinical benefit rate (CR + PR + SD) by RECIST for extracranial disease in each of the cohorts determined by treatment and primary cancer type. IV. To evaluate the duration of response by BM-RANO in each of the cohorts determined by treatment and primary cancer type. V. To evaluate the duration of response by RECIST in each of the cohorts determined by treatment and primary cancer type. VI. To evaluate the progression-free survival for intracranial disease in each of the cohorts determined by treatment and primary cancer type. VII. To evaluate the progression-free survival for extracranial disease in each of the cohorts determined by treatment and primary cancer type. VIII. To evaluate the site of first progression (CNS versus [vs] non-CNS) in each of the cohorts determined by treatment and primary cancer type. IX. To evaluate the overall survival in each of the cohorts determined by treatment and primary cancer type. X. To evaluate the toxicity profile of agents in patients with brain metastases in each of the cohorts determined by treatment and primary cancer type. OUTLINE: Patients are assigned to 1 of 3 arms. ARM I (CDK GENE MUTATION): Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II (PI3K GENE MUTATION): Patients receive PI3K inhibitor paxalisib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM III (NTRK/ROS1 GENE MUTATION): Patients receive entrectinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 8 weeks for 2 years, then every 3 months for years 3-4, and then every 6 months thereafter for up to 5 years after registration. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Sammons S, Van Swearingen AED, Anders CK. Receptor discordance in breast cancer brain metastases: when knowledge is power. Neuro Oncol. 2020 Aug 17;22(8):1060-1061. doi: 10.1093/neuonc/noaa131. | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
150 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | June 2025 | ||||
Estimated Primary Completion Date | October 2024 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria: PRE-REGISTRATION ELIGIBILITY CRITERIA (ALL PATIENTS) • Tissue available for biomarker testing (any brain metastasis tissue and extracranial site from any prior resection or biopsy). REGISTRATION ELIGIBILITY CRITERIA (ALL PATIENTS)
ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR PAXALISIB ARM
ADDITIONAL REGISTRATION ELIGIBILITY CRITERION FOR ENTRECTINIB ARM • Concurrent use of H2 receptor antagonists, receptor antagonists, proton pump inhibitors (PPIs), and/or antacids are prohibited. ADDITIONAL REGISTRATION ELIGIBILITY CRITERION FOR ABEMACICLIB ARM
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03994796 | ||||
Other Study ID Numbers ICMJE | A071701 NCI-2019-00744 ( Registry Identifier: NCI Clinical Trial Reporting Program ) U10CA180821 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Alliance for Clinical Trials in Oncology | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | Alliance for Clinical Trials in Oncology | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Alliance for Clinical Trials in Oncology | ||||
Verification Date | June 2022 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |