Trial Outcomes & Findings for Brigatinib Before Brain Irradiation Trial (B3i Trial) (NCT NCT04634110)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

1 participants

Primary outcome timeframe

13-week MRI ±7 days

Results posted on

2022-10-24

Participant Flow

Participant milestones

Participant milestones
Measure	Patients With ALK+ NSCLC and Brain Metastases 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.
Overall Study STARTED	1
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Brigatinib Before Brain Irradiation Trial (B3i Trial)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Patients With ALK+ NSCLC and Brain Metastases n=1 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	57 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	1 participants n=5 Participants

PRIMARY outcome

Timeframe: 13-week MRI ±7 days

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.

Outcome measures

Outcome measures
Measure	Patients With ALK+ NSCLC and Brain Metastases n=1 Participants 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.
Number of Participants Who Meet Disease Control Rate (DCR) Criteria of Brain Metastases at 3 Months	1 Participants

SECONDARY outcome

Timeframe: up to 24 months

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 24 months

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 24 months

Population: 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 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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 24 months

Population: 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 at any site using RANO-BM for intracranial disease and RECIST for extracranial disease and rates at follow up intervals

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 24 months

Population: 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.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 24 months

Population: 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.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 24 months

Population: 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.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 24 months

Population: 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 whole brain-radiotherapy (WBRT) and rates at follow up intervals

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 24 months

Population: 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.

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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 24 months

Population: 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.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 24 months

Population: 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.

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

Outcome measures

Outcome data not reported

Adverse Events

Patients With ALK+ NSCLC and Brain Metastases

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Patients With ALK+ NSCLC and Brain Metastases n=1 participants at risk 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.
Musculoskeletal and connective tissue disorders Non-Cardiac Chest Pain	100.0% 1/1 • Number of events 3 • 13 weeks
General disorders Somnolence	100.0% 1/1 • Number of events 1 • 13 weeks
Cardiac disorders Sinus Tachycardia	100.0% 1/1 • Number of events 1 • 13 weeks
Gastrointestinal disorders Constipation	100.0% 1/1 • Number of events 1 • 13 weeks
Blood and lymphatic system disorders Hyponatremia	100.0% 1/1 • Number of events 1 • 13 weeks
Blood and lymphatic system disorders CPK increased	100.0% 1/1 • Number of events 1 • 13 weeks
Gastrointestinal disorders Diarrhea	100.0% 1/1 • Number of events 1 • 13 weeks
Respiratory, thoracic and mediastinal disorders Vocal Cord Paralysis	100.0% 1/1 • Number of events 1 • 13 weeks
Skin and subcutaneous tissue disorders xerosis	100.0% 1/1 • Number of events 1 • 13 weeks
Gastrointestinal disorders Nausea	100.0% 1/1 • Number of events 1 • 13 weeks

Additional Information

Dr. Chad Rusthoven

University of Colorado Hospital

Phone: 720-516-0150

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place