Brigatinib Before Brain Irradiation Trial (B3i Trial)

NCT04634110 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 19-2862.ccP30CA046934
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Brain Metastases; Lung Cancer

Outcome Measures

Primary Outcomes (1)

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

  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.

  13-week MRI ±7 days

Secondary Outcomes (9)

• Time Until Progression With Brigatinib Alone (Part 1)

  up to 24 months

• Time Until Progression With Brigatinib Alone (Part 2)

  up to 24 months

• Time Until Progression With Brigatinib Alone (Part 3)

  up to 24 months

• Time Until Progression With Brigatinib Alone (Part 4)

  up to 24 months

• Overall Survival With a Strategy of Brigatinib Alone

  up to 24 months

Other Outcomes (2)

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

  up to 24 months

• Characterization of Corticosteroid Administration Before and After Brigatinib Initiation

  up to 24 months

Study Arms (1)

Patients with ALK+ NSCLC and brain metastases

EXPERIMENTAL

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.

Drug: Brigatinib

Interventions

Brigatinib DRUG

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision to sign and date the consent form.
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Ability to take and retain oral medications.
• Age ≥18 years.
• Patients with ALK+ lung cancer with evidence of ≥1 previously untreated brain metastases on brain MRI. Prior therapy (radiation or surgery) for brain metastases is allowed. However, patients must have ≥1 previously untreated at the time of enrollment.
• Patients may be ALK TKI naïve OR have had prior crizotinib therapy.
• Patients may be included if they are asymptomatic from their brain metastases (RTOG/EORTC grade 0) or if they have mild symptoms from their brain metastases not to exceed RTOG/ EORTC grade 1 or 2 (Grade 1: Fully functional status (i.e. able to work) with minor neurological findings, no medication needed; Grade 2: Neurological findings present sufficient to require home care / nursing assistance may be required / medications including steroids/anti-seizure agents may be required) (Cox, James D., et al "Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC)." International Journal of Radiation Oncology• Biology• Physics 31.5 (1995): 1341-1346).
• Neurologically symptomatic patients must not require immediate surgical or radiation therapy for their symptoms, as decided by an investigator.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Have adequate organ function, as determined by
• ALT/AST ≤2.5 × upper limit of normal (ULN); ≤5 × ULN is acceptable if liver metastases are present
• Total serum bilirubin ≤1.5 × ULN (\<3.0×ULN for patients with Gilbert syndrome)
• Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, using the modification of diet in renal disease (MDRD) equation
• Serum lipase/amylase ≤1.5 × ULN
• Absolute neutrophil count (ANC) ≥1.5 × 109/L

You may not qualify if:

• Patients who have received prior brigatinib therapy or other CNS-penetrant ALK TKIs, including alectinib, lorlatinib, or ceritinib.
• RTOG/EORTC Acute CNS symptoms, grade 3 and 4 (Grade 3: Neurological findings requiring hospitalization for initial management; Grade 4: Serious neurological impairment that includes paralysis, coma, or seizures \> 3 per week despite medication / hospitalization required).
• Currently pregnant, planning a pregnancy during the study period, or breastfeeding.
• Have clinically significant, uncontrolled cardiovascular disease per investigator, specifically including, but not restricted to:
• Myocardial infarction (MI) within 6 months prior to the first dose of study drug
• Unstable angina within 6 months prior to first dose of study drug
• Clinically significant congestive heart failure (CHF) within 6 months prior to first dose of study drug
• History of clinically significant atrial or ventricular arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician
• Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose of study drug
• Have uncontrolled hypertension per the investigator. Patients with persistent hypertension of systolic ≥140 or diastolic ≥90 mm Hg should be under treatment on study entry to control blood pressure.
• Have a history or the presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis.
• Have an ongoing or active infection, including, but not limited to, the requirement for intravenous (IV) antibiotics.
• Have a known history of human immunodeficiency virus (HIV) infection. Testing is not required in the absence of history.
• Have a known or suspected hypersensitivity to brigatinib or its excipients.
• Additional systemic therapies for the treatment of lung cancer may not be taken concomitantly with brigatinib (eg, TKIs, immunotherapy, chemotherapy). No washout period is required for prior therapy.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

City of Hope

Duarte, California, 91010, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Lung Neoplasms

Interventions

brigatinib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

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

Results Point of Contact

• Title: Dr. Chad Rusthoven
• Organization: University of Colorado Hospital

chad.rusthoven@cuanschutz.edu

720-516-0150

Study Officials

• Chad Rusthoven, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2020
• First Posted: November 18, 2020
• Study Start: November 17, 2020
• Primary Completion: April 14, 2022
• Study Completion: April 14, 2022
• Last Updated: October 24, 2022
• Results First Posted: October 24, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)