Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Lung Neoplasms

Neoplasm Metastasis

Brain Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Crizotinib

Tyrosine Kinase Inhibitors

Alectinib

Ceritinib

Tyrosine

Including patients with brain metastases from ALK (anaplastic lymphoma kinase) positive NSCLC (non-small cell lung cancer), who are either neurologically asymptomatic or who have only mild neurologic symptoms (RTOG \[Radiation therapy Oncology Group\] acute neurologic morbidity score 0-2) from their brain metastases, who are TKI (tyrosine kinase inhibitor) naïve or who have had prior exposure to crizotinib, but who are naïve to brigatinib and other ALK TKIs including alectinib, lorlatinib, and ceritinib.

At day 1, all patients will be started on brigatinib 90 mg daily for 7 days, before escalating to 180 mg daily thereafter as tolerated.

Brigatinib

Chad Rusthoven, MD

This is a single arm phase II study of brigatinib alone for patients with brain metastases from anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC), who have either not been treated previously with a tyrosine kinase inhibitor (TKI) targeting ALK or who have had prior exposure to crizotinib.

In this single-arm phase II trial, patients with brain metastases from ALK+ NSCLC will be treated with brigatinib alone without upfront brain irradiation. Patients will have close monitoring with clinical follow up visits and brain magnetic resonance imaging (MRI) surveillance, which will maximize safety and allow for early treatment if disease progression is observed. If brigatinib alone can demonstrate high rates of CNS disease control, these data could support a strategy of upfront brigatinib alone for carefully selected patients with brain metastases from ALK+ NSCLC.

Brigatinib Before Brain Irradiation Trial (B3i Trial)

Brigatinib Before Brain Irradiation Trial (B3i Trial): A Phase II Trial of Brigatinib Alone for Brain Metastases From ALK+ Lung Cancer

Evaluation of cfDNA at baseline and progression to correlate with clinical outcomes, including incidence of disease recurrence per RANO-BM and RECIST 1.1, survival status by percentage of patients alive at 2 years, and patient rating of quality of life per EORTC QLQ-BN20 and EORTC QLQ-C30 questionnaires.

Quantification of the agent and dosage of corticosteroids at each study assessment

DCR is defined as complete response (CR), partial response (PR), or stable disease (SD) as defined by the RANO-BM (Response Assessment in Neuro-Oncology Criteria - Brain Metastases) criteria.

Time until any CNS progressive disease (PD) by RANO-BM criteria and rates at follow up intervals

Time until any local PD (i.e., in brain lesions identified at the time of enrollment) by RANO-BM criteria and rates at follow up intervals

Time until any distant brain PD (i.e., new brain lesions that were not present at the time of enrollment) by RANO-BM criteria and rates at follow up intervals

Time until progression at any site using RANO-BM for intracranial disease and RECIST for extracranial disease and rates at follow up intervals

Time until death from any cause and rates at follow up intervals

Defined as time to intracranial progression as a component of cause of death and rates at follow up intervals

Cumulative rate of best responses individually for complete response (CR), partial response (PR), stable disease (SD), by RANO-BM criteria

Time until the administration of whole brain-radiotherapy (WBRT) and rates at follow up intervals

Quality of life will be assessed using standardized QOL metrics (EORTC QLQ C30/BN 20)

National Cancer Institute (NCI)

University of Colorado, Denver

Including patients with brain metastases from ALK (anaplastic lymphoma kinase) positive NSCLC (non-small cell lung cancer), who are either neurologically asymptomatic or who have only mild neurologic symptoms (RTOG \[Radiation therapy Oncology Group\] acute neurologic morbidity score 0-2) from their brain metastases, who are TKI (tyrosine kinase inhibitor) naïve or who have had prior exposure to crizotinib, but who are naïve to brigatinib and other ALK TKIs including alectinib, lorlatinib, and ceritinib.

Brigatinib: At day 1, all patients will be started on brigatinib 90 mg daily for 7 days, before escalating to 180 mg daily thereafter as tolerated.

Patients With ALK+ NSCLC and Brain Metastases

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

1 subject enrolled then study terminated due to low accrual. No further analyses completed.

Dr. Chad Rusthoven

Number of Participants Who Meet Disease Control Rate (DCR) Criteria of Brain Metastases at 3 Months

Trial was terminated early due to low accrual. No data were collected for this outcome measure because the patient was only followed for 13 weeks, and progression did not occur during this time.

Time Until Progression With Brigatinib Alone (Part 1)

Time Until Progression With Brigatinib Alone (Part 2)

Time Until Progression With Brigatinib Alone (Part 3)

Time Until Progression With Brigatinib Alone (Part 4)

Trial was terminated early due to low accrual. No data were collected for this outcome measure because the patient was only followed for 13 weeks and did not die.

Overall Survival With a Strategy of Brigatinib Alone

Trial was terminated early due to low accrual. No data were collected for this outcome measure because the patient was only followed for 13 weeks, and neither progression nor death occurred during this time.

Time Until Brain Metastases-Specific Mortality

Trial was terminated early due to low accrual. No data were collected for this outcome measure because the patient was only followed for 13 weeks.

Brain Metastases Objective Response Rates (ORR) With Brigatinib Alone

Trial was terminated early due to low accrual. No data were collected for this outcome measure because the patient was only followed for 13 weeks and did not receive WBRT before trial termination.

Time Until the Administration of WBRT With Brigatinib Alone

Trial was terminated early due to low accrual. No scores were computed for this outcome measure because the patient was only followed for 13 weeks out of the intended 104 weeks and longitudinal changes could not be analyzed.

Longitudinal Changes in Quality of Life With Brigatinib Alone

Trial was terminated early due to low accrual. No data were collected for this outcome measure because the patient was only followed for 13 weeks, and no progression occurred during this time.

Analysis of Blood at Baseline and at Progression to Correlate With Clinical Outcomes

Trial was terminated early due to low accrual. No data were collected for this outcome measure because the patient was only followed for 13 weeks and had not been administered any corticosteroids during this time.

Spots Global Cancer Trial Database for Brigatinib Before Brain Irradiation Trial (B3i Trial)

Trial Identification

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Study Description

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