AzTrials
AzTrials

Locally Advanced Lung Non-Small Cell CarcinomaPhase 1NCT04227028

Brigatinib and Bevacizumab for the Treatment of ALK-Rearranged Locally Advanced, Metastatic, or Recurrent NSCLC

A Phase 1 study testing Bevacizumab and Brigatinib in people with Locally Advanced Lung Non-Small Cell Carcinoma and Metastatic Lung Non-Small Cell Carcinoma, run by City of Hope Medical Center at 6 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase Ib trial studies the side effects and best dose of brigatinib and how well it works with bevacizumab in treating patients with ALK-rearranged non-small cell lung cancer that has spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic) or has come back (recurrent). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bevacizumab and Brigatinib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
6 sitesUnited States
Study dates
9 Mar 2020to 25 Mar 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Patients must have a histologically documented (either primary or metastatic site) diagnosis of locally advanced, recurrent, or metastatic ALK rearranged non-small cell lung cancer (NSCLC)
  • Patients must have shown progression on ALK-directed therapy
  • Note: Patients may have received more than one prior line of therapy, however, at least one of these must be an ALK-directed line of therapy
  • Patients must have measurable disease as per appropriate guidelines by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
  • Patients must have the ability to understand and the willingness to sign a written consent prior to registration in the study
  • Patients with asymptomatic (as determined by the treating investigator) CNS metastasis are eligible for participation
Show all 34Show fewer
  • Note: Patients with leptomeningeal disease are not eligible
  • Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Patient life expectancy of more than 12 weeks
  • Patients must have adequate organ and bone marrow function during screening, as defined below:
  • Absolute neutrophil count >= 1.5 x 10^9/L
  • Hemoglobin >= 9 g/dL
  • Note: Transfusions are permitted (transfusions >= 1 day to registration are allowed)
  • Platelets >= 75 x 10^(9)/L
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Note: Patients with Gilbert syndrome are exempt
  • Alanine amino transferase and aspartate aminotransferase =< 2.5 x ULN
  • Note: =< 5 x ULN is acceptable if liver metastases are present
  • Serum lipase =< 1.5 x ULN
  • Creatine kinase (CPK) < 5.0 x ULN
  • Estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease (MDRD) equation >= 30 mL/min/1.73 m^2
  • Patients must meet criteria for appropriate contraception, listed as follows
  • Female patients must meet at least one of the following criteria:
  • Are postmenopausal with last menstrual period at least 1 year before registration, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential,
  • Agree to practice 1 highly effective method of non-hormonal contraception and one additional effective (barrier) method at the same time, from the time of signing the informed consent through 180 days after the last dose of study drug, or
  • Agree to practice true abstinence, when is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g. calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
  • Agree not to donate eggs (ova) during the course of this study or 180 days after receiving their last dose of study drug. Agree not to breast-feed for the duration of treatment through 6 months post treatment
  • Note: Female patients who are pregnant, planning a pregnancy, or nursing are not eligible
  • Male patients, even if surgically sterilized (i.e. status post-vasectomy), must:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 180 days after the last dose of study drug, or
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g. calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception. Female and male condoms should not be used together.)
  • Agree not to donate sperm during the course of this study or within 180 days after receiving their last dose of study drug

Who cannot join

  • Patients who have had prior systemic anticancer or radiotherapy =< 14 days prior to first dose of brigatinib are not eligible
  • Patients may not have received any other investigational agents =< 14 days prior to first dose of brigatinib
  • Patients who have received antineoplastic monoclonal antibodies within 21 days of the first dose of brigatinib, and tyrosine kinase inhibitors (TKIs) within 7 days of the first dose of brigatinib are not eligible
  • Patients with prior severe infusion reaction to bevacizumab are not eligible
  • Patients with other coexisting malignancies or malignancies diagnosed within the previous 3 years that per the investigator are at high-risk of relapse within one year are not eligible
  • Note: Exceptions to this include non-melanoma skin cancer, cervical cancer in-situ, well-differentiated thyroid cancer or prostate cancer. Other cancers that per assessment of the principal investigator (PI) are not prognosis-limiting can be allowed after review by the PI. If there is no evidence of disease for at least 3 years, patients may be eligible
Show all 34Show fewer
  • Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
  • Uncontrolled pulmonary, renal, or hepatic dysfunction,
  • Ongoing or active infection requiring systemic treatment including hepatitis B and hepatitis C,
  • Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection,
  • Note: Patients who have isolated positive hepatitis B core antibody (i.e. in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load
  • Active uncontrolled infection or severe infectious disease such as severe pneumonia, meningitis, or septicemia,
  • Known active or chronic viral hepatitis or human immunodeficiency virus (HIV),
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints are not eligible
  • Female patients who are pregnant, planning a pregnancy, or nursing or have a positive serum pregnancy test within 7 days prior registration (without subsequent negative vaginal ultrasound) are not eligible
  • Patients who have had major surgery within 30 days of registration, are not eligible
  • Note: Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed
  • Patients who have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to the following are not eligible:
  • Myocardial infarction within 6 months before registration
  • Unstable angina within 6 months before registration
  • Congestive heart failure within 6 months before registration
  • History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician
  • Any history of clinically significant ventricular arrhythmia
  • Patients who have had a cerebrovascular accident or transient ischemic attack within 6 months before registration are not eligible
  • Patients who have uncontrolled hypertension are not eligible
  • Note: Patients with hypertension per the opinion of the treating investigator should be under treatment on study entry to control blood pressure
  • Patients who have the presence at baseline of unresolved pulmonary interstitial disease that is grade 3 or 4 are not eligible
  • Patients who have a history of or the presence at baseline of grade 2 or higher uncontrolled drug related pneumonitis, or radiation pneumonitis are not eligible
  • Patients who have malabsorption syndrome or other gastrointestinal (GI) illness that could affect oral absorption of brigatinib in the opinion of the treating Investigator are not eligible
  • Patients with recent history of pulmonary embolism, or untreated deep vein thrombosis in the last 3 months are not eligible
  • Note: Patients may be eligible if they have received at least 3 months of anticoagulation for a deep vein thrombosis
  • Patients who have a known or suspected hypersensitivity to brigatinib, or its excipients are not eligible
  • Patients who have received systemic treatment with strong cytochrome P-450 (CYP)3A inhibitors, strong CYP3A inducers or moderate CYP3A inducers within 14 days before registration are not eligible

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • City of Hope Medical Center

    Duarte, California, 91010

  • Penn State Cancer Institute

    Hershey, Pennsylvania, 17033

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

Other trials in United States

About this study

Official title: Phase Ib Study of Brigatinib Plus Bevacizumab in Patients With ALK-Rearranged Non-Small Cell Lung Cancer (NSCLC) Who Have Previously Progressed on Prior ALK-Directed Therapy

This phase Ib trial studies the side effects and best dose of brigatinib and how well it works with bevacizumab in treating patients with ALK-rearranged non-small cell lung cancer that has spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic) or has come back (recurrent). Brigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known if brigatinib and bevacizumab will work better in treating patients with ALK-rearranged non-small cell lung cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine toxicity and tolerability, and the maximum tolerated dose (MTD) of brigatinib and bevacizumab in patients with ALK rearranged non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

  1. To describe the dose-limiting toxicities of brigatinib in combination with bevacizumab.

II. To estimate overall response rate (ORR) to treatment with brigatinib and bevacizumab.

III. To estimate the duration of response as defined by the time of first documented clinical benefit to the time of progression.

IV. To estimate patient survival by measuring progression free survival (PFS) as defined by the time from treatment initiation to documented disease progression or death from any cause. Overall survival (OS) as defined by the time from treatment initiation until death due to any cause.

EXPLORATORY OBJECTIVES:

  1. To identify predictive biomarkers using genetics and tumor immunology-based assessment platforms.

Ia. Analysis with next-generation sequencing (NGS) to identify predictive biomarkers for response using tissue and cerebral spinal fluid (CSF) (optional for patients with brain metastases).

Ib. Tumor tissue will be obtained at baseline, and cell free deoxyribonucleic acid (DNA) (cfDNA)/cell tumor DNA (ctDNA) obtained at baseline and the time of progression or study completion will be evaluated for genomic alterations and biomarkers.

II. Evaluation of central nervous system (CNS) penetration through cerebral spinal fluid (CSF) obtained by lumbar puncture on cycle 2 day 1 (C2D1) (with time matched pharmacokinetic [PK] blood draw), and at progression or study completion for consenting patients (optional).

OUTLINE: This is a dose-escalation study of brigatinib.

Patients receive brigatinib orally (PO) once daily (QD) on days 1-28 of cycle 1 and days 1-21 of subsequent cycles. Patients also receive bevacizumab intravenously (IV) on day 8 of cycle 1 and day 1 of subsequent cycles. Starting cycle 2, cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, 3, 6, 9, and 12 months, then every 6 months for up to 3 years.

Being tested
Bevacizumab, Brigatinib
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

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

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • BrigatinibDrug

    Also called Alunbrig, AP 26113, AP-26113, AP26113

    Given PO

Study groups in NCT04227028
Study groupRoleWhat they receive
Treatment (brigatinib, bevacizumab)ExperimentalPatients receive brigatinib PO QD on days 1-28 of cycle 1 and days 1-21 of subsequent cycles. Patients also receive bevacizumab IV on day 8 of cycle 1 and day 1 of subsequent cycles. Starting cycle 2, cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Bevacizumab; Drug: Brigatinib

What is being measured

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

  1. Incidence of adverse events

    Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) 5.0.

    Measured: Within 30 days of treatment discontinuation or prior to start of next treatment

  2. Maximum tolerated dose

    Will be determined by dose limiting toxicities and assessed using CTCAE 5.0.

    Measured: Up to 28 days

Secondary outcomes (5)

  1. Dose-limiting toxicities

    Will be evaluated in the first 28 days of treatment for the first 6-12 patients in the safety cohort to determine any dose limiting toxicities at this dose.

    Measured: Up to 28 days

  2. Overall response rate

    Will be defined as the overall number of patients with complete response plus partial response and assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. A proportion and exact 95% binomial confidence interval will be calculated.

    Measured: Up to 3 years

  3. Duration of response

    Will be analyzed using medians and ranges.

    Measured: From first documentation of clinical benefit from treatment to the time of documentation of progressive disease or death, whichever comes first, assessed up to 3 years

  4. Progression-free survival (PFS)

    Will be estimated using the Kaplan-Meier method. If there is a change of treatment in multiple patients, then a competing risk cumulative incidence for PFS will be calculated using the treatment change as a competing risk.

    Measured: From treatment initiation to the time of documented disease progression or death from any cause, whichever comes first, assessed up to 3 years

  5. Overall survival (OS)

    Will be estimated using the Kaplan-Meier method.

    Measured: From treatment initiation until death due to any cause, assessed up to 3 years

Timeline

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

  1. First posted13 Jan 2020
  2. Study start9 Mar 2020
  3. Primary completion25 Mar 2027 (estimated)
  4. Study completion25 Mar 2027 (estimated)

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04227028
Sponsor's protocol ID
20495
Other IDs
STU00211030, NU 19L01, P30CA060553, NCI-2019-08726
Status last verified
Jun 2026
First submitted
10 Jan 2020
Last updated
1 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bevacizumab and Brigatinib in people with Locally Advanced Lung Non-Small Cell Carcinoma and Metastatic Lung Non-Small Cell Carcinoma, run by City of Hope Medical Center at 6 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 34 inclusion and 34 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: under way, not looking for participants, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Incidence of adverse events (time frame: Within 30 days of treatment discontinuation or prior to start of next treatment). The study lists 2 primary outcomes in all. 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 NCT04227028.

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 1 Jul 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in