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Brain MetastasesPhase 2NCT04634110

Brigatinib Before Brain Irradiation Trial (B3i Trial)

A Phase 2 study testing Brigatinib in people with Brain Metastases and Lung Cancer, run by University of Colorado, Denver at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Brain Metastases, Lung Cancer
What is being tested?
Brigatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
3 sitesUnited States
Study dates
17 Nov 2020to 14 Apr 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • Platelet count ≥75 × 109/L
  • Hemoglobin ≥9 g/dL
  • For females of childbearing potential, have a negative pregnancy test documented prior to initiating brigatinib.
  • For female and male patients who are fertile, agree to use 2 effective methods of contraception with their sexual partners from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse. Brigatinib may decrease effectiveness of hormonal contraceptives, therefore, women are recommended to use non-hormonal methods of contraception. Highly effective non-hormonal birth control for women of child bearing potential with male partners includes:
  • Sexual abstinence (no sexual intercourse)
  • Intrauterine device (IUD) or intrauterine system (IUS)
  • Bilateral tubal ligation (both tubes tied)
  • Vasectomized partner
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy) must agree to 1 of the following:
  • Practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or completely abstain from heterosexual intercourse.

Who cannot join

  • 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
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  • 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.
  • Have malabsorption syndrome or other GI illness that could affect oral absorption of brigatinib.
  • Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of brigatinib.
  • Received systemic treatment with strong cytochrome p-450 (cyp)3a inhibitors, strong cyp3a inducers, or moderate cyp3a inducers within 14 days before enrollment.
  • Had major surgery within 30 days of the first dose of brigatinib. Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.
  • Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated nonmelanoma skin cancer or cervical cancer in situ; definitively treated nonmetastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • City of Hope

    Duarte, California, 91010

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

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

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.

Read the detailed description

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.

Being tested
Brigatinib
Medical subject headings
Brain Neoplasms, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BrigatinibDrug

    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.

Study groups in NCT04634110
Study groupRoleWhat they receive
Patients with ALK+ NSCLC and brain metastasesExperimentalIncluding 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.
Receives: Drug: Brigatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 13-week MRI ±7 days

Secondary outcomes (9)

  1. Time Until Progression With Brigatinib Alone (Part 1)

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

    Measured: up to 24 months

  2. Time Until Progression With Brigatinib Alone (Part 2)

    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

    Measured: up to 24 months

  3. Time Until Progression With Brigatinib Alone (Part 3)

    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

    Measured: up to 24 months

  4. Time Until Progression With Brigatinib Alone (Part 4)

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

    Measured: up to 24 months

  5. Overall Survival With a Strategy of Brigatinib Alone

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

    Measured: up to 24 months

  6. Time Until Brain Metastases-Specific Mortality

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

    Measured: up to 24 months

  7. Brain Metastases Objective Response Rates (ORR) With Brigatinib Alone

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

    Measured: up to 24 months

  8. Time Until the Administration of WBRT With Brigatinib Alone

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

    Measured: up to 24 months

  9. Longitudinal Changes in Quality of Life With Brigatinib Alone

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

    Measured: up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Nov 2020
  2. Study start17 Nov 2020
  3. Primary completion14 Apr 2022
  4. Study completion14 Apr 2022

Why it stopped: Low accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04634110
Sponsor's protocol ID
19-2862.cc
Other IDs
P30CA046934
Status last verified
Sep 2022
First submitted
23 Oct 2020
Last updated
24 Oct 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brigatinib in people with Brain Metastases and Lung Cancer, run by University of Colorado, Denver at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Meet Disease Control Rate (DCR) Criteria of Brain Metastases at 3 Months (time frame: 13-week MRI ±7 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04634110.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2022.

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