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Advanced Lung CarcinomaPhase 1NCT03707938

Local Consolidative Therapy and Brigatinib in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer

A Phase 1 study testing Brigatinib and Local Consolidation Therapy in people with Advanced Lung Carcinoma and ALK Gene Rearrangement, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

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

Official record

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Trial summary

This early phase I trial studies the side effects and how well local consolidative therapy (LCT) and brigatinib works in treating patients with non-small cell lung cancer that is stage IV or has come back (recurrent). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Brigatinib and Local Consolidation Therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteUnited States
Study dates
18 Dec 2018to 28 Jan 2026
Phase
Phase 1

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

  • Histologically or cytologically confirmed diagnosis of stage IV NSCLC (or recurrent NSCLC not a candidate for definitive multimodality therapy)
  • Documented ALK re-arrangement as detected by: (1) FISH, (2) IHC, (3) tissue NGS, or (4) cfDNA NGS
  • Subjects can be enrolled as (1) TKI naïve or (2) after ≤ 8 weeks of first-line brigatinib treatment without disease progression.
  • Candidate for local consolidative therapy to at least one site of residual disease
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Males or females aged at least 18 years.
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  • Adequate organ function laboratory values, defined as:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L or at least 1500/mm3 or at least 1.5 x 109/L
  • Platelet count at least 75,000/mm3 or at least 75 x 109/L
  • Hemoglobin (Hb) at least 9 g/dL (or 5.69 mmol/L) at baseline
  • Serum creatinine ≤ 1.5 × ULN or ≥ 60 mL/minute for subjects with creatinine levels > 1.5 × the institutional ULN
  • Serum total bilirubin less than or equal to ≤ 1.5 × ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 × ULN
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN except for subjects with liver mets for whom ALT and AST should be ≤ 5× ULN
  • International Normalized Ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated PTT (aPTT) ≤ 1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulant
  • Female patients of childbearing potential must have a negative pregnancy test documented at time of screening.
  • Female patients who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to use a highly effective method of contraception 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
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or
  • Agree to completely abstain from heterosexual intercourse
  • Have normal QT interval on screening ECG evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ≤450 milliseconds (msec) in males or ≤470 msec in females.
  • Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.

Who cannot join

  • Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 2 years elapsed since the diagnosis of the other primary malignancy.
  • Previously received any prior TKI, including ALK-targeted TKIs. Note: on-going first-line brigatinib use as specified in the Inclusion criteria is allowed.
  • Previously received more than 1 regimen of chemotherapy or immunotherapy for locally advanced or metastatic disease. Note that history of consolidative immunotherapy after concurrent chemoradiotherapy (for locally advanced disease) is allowed.
  • Symptomatic CNS metastasis. Asymptomatic CNS disease requiring increasing dose of corticosteroids within 7 days prior to study enrollment is also not permitted.
  • Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression are allowed.
  • The presence of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis at screening.
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  • Have a known or suspected hypersensitivity to brigatinib or its excipients.
  • Have malabsorption syndrome or other gastrointestinal (GI) illness or condition that could affect oral absorption of the study drug.
  • Be pregnant, planning a pregnancy, or breastfeeding.
  • Have significant, uncontrolled, or active cardiovascular disease, 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
  • Decompensated congestive heart failure (CHF) within 6 months prior to first dose of study drug
  • History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician
  • Any history of ventricular arrhythmia
  • Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose of study drug
  • Have uncontrolled hypertension. Patients with hypertension should be under treatment on study entry to control blood pressure
  • 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 any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the study drug.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: BRIGHTSTAR: A Pilot Trial of Local Consolidative Therapy (LCT) With Brigatinib in Tyrosine Kinase Inhibitor-Naive ALK-Rearranged Advanced NSCLC

This early phase I trial studies the side effects and how well local consolidative therapy (LCT) and brigatinib works in treating patients with non-small cell lung cancer that is stage IV or has come back (recurrent). Giving LCT, such as surgery and/or radiation, after initial treatment may kill any remaining tumor cells. Brigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving LCT and brigatinib may work better in treating patients with non-small cell lung cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety, tolerability, and feasibility of brigatinib with local consolidative therapy (LCT) in tyrosine kinase inhibitor-naive ALK-rearranged advanced (non-small cell lung cancer) NSCLC.

SECONDARY OBJECTIVES:

  1. To determine progression-free survival (PFS) using modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in advanced ALK+ NSCLC patients treated with local consolidative therapy (LCT) after achieving stable disease or partial response with first-line brigatinib treatment.

II. To determine overall survival (OS).

III. To assess time to progression (TTP) of non-LCT lesions.

EXPLORATORY OBJECTIVES:

  1. To assess time to appearance of new metastatic lesion(s).

II. To determine the utility of pre-treatment, pre-LCT, and post-LCT circulating free tumor deoxyribonucleic acid (DNA) (cfDNA) as a potential prognostic and predictive biomarkers.

II. To evaluate potential impact of LCT on mechanisms of ALK resistance with molecular analysis of post-progression biopsies.

OUTLINE:

Patients receive brigatinib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo LCT for up to 3 weeks in the absence of disease progression or unacceptable toxicity. Within 7 days after completion of LCT, patients receive brigatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 3 months for up to 2 years.

Being tested
Brigatinib, Local Consolidation Therapy
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.

  • BrigatinibDrug

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

    Given PO

  • Local Consolidation TherapyProcedure or surgery

    Also called LCT, Local Consolidative Therapy

    Undergo local consolidative therapy

Study groups in NCT03707938
Study groupRoleWhat they receive
Treatment (brigatinib, LCT)ExperimentalPatients receive brigatinib PO QD on days 1-28. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo LCT for up to 3 weeks in the absence of disease progression or unacceptable toxicity. Within 7 days after completion of LCT, patients receive brigatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Brigatinib; Procedure: Local Consolidation Therapy

What is being measured

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

  1. Incidence of adverse events

    Toxicity data will be summarized using frequency tables. Associations between the types and severity of toxicity and treatment will be evaluated as well.

    Measured: Up to 2 years

Secondary outcomes (3)

  1. Progression-free survival (PFS)

    The median PFS will be calculated and presented with 2-sided 80% confidence interval (CI). Kaplan-Meier survival probabilities will be plotted over time.

    Measured: From the date of brigatinib treatment initiation until disease progression or death, assessed up to 2 years

  2. Overall survival (OS)

    The median OS will be calculated and presented with 2-sided 80% CI. Kaplan-Meier survival probabilities will be plotted over time.

    Measured: From the date of brigatinib treatment initiation until date of death from any cause, assessed up to 2 years

  3. Time to progression of non-local consolidative therapy (LCT) lesion

    The median time to progression of non-LCT lesion will be calculated and presented with 2-sided 80% CI. Kaplan-Meier survival probabilities will be plotted over time.

    Measured: From the date of brigatinib treatment initiation until progression of a baseline lesion not treated with radiation or surgery, assessed up to 2 years

Timeline

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

  1. First posted16 Oct 2018
  2. Study start18 Dec 2018
  3. Primary completion28 Jan 2026 (estimated)
  4. Study completion28 Jan 2026 (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
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03707938
Sponsor's protocol ID
2018-0598
Other IDs
NCI-2018-02099, 2018-0598
Status last verified
Oct 2025
First submitted
12 Oct 2018
Last updated
3 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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