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

NCT03707938 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2018-0598NCI-2018-02099
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Advanced Lung Carcinoma; ALK Gene Rearrangement; Lung Non-Small Cell Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (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.

  Up to 2 years

Secondary Outcomes (3)

• Progression-free survival (PFS)

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

• Overall survival (OS)

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

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

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

Other Outcomes (2)

• Time to appearance of new metastatic lesion(s) (TANM)

  From the date of brigatinib treatment initiation until development of a new lesion, assessed up to 2 years

• Potential prognostic and predictive biomarkers

  Up to 2 years

Study Arms (1)

Treatment (brigatinib, LCT)

EXPERIMENTAL

Patients 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.

Drug: Brigatinib; Procedure: Local Consolidation Therapy

Interventions

Brigatinib DRUG

Given PO

Also known as: Alunbrig, AP 26113, AP-26113, AP26113

Treatment (brigatinib, LCT)

Local Consolidation Therapy PROCEDURE

Undergo local consolidative therapy

Also known as: LCT, Local Consolidative Therapy

Treatment (brigatinib, LCT)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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 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.
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

brigatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yasir Y Elamin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2018
• First Posted: October 16, 2018
• Study Start: December 18, 2018
• Primary Completion: January 28, 2026
• Study Completion: January 28, 2026
• Last Updated: November 3, 2025

Record last verified: 2025-10

Locations

US (1)