Clinical Trials /

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

NCT03707938

Description:

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. 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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Local Consolidative Therapy and Brigatinib in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer
  • Official Title: BRIGHTSTAR:A Pilot Trial of Local Consolidative Therapy (LCT) With Brigatinib in Tyrosine Kinase Inhibitor-Naive ALK-Rearranged Advanced NSCLC

Clinical Trial IDs

  • ORG STUDY ID: 2018-0598
  • SECONDARY ID: NCI-2018-02099
  • SECONDARY ID: 2018-0598
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03707938

Conditions

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

Interventions

DrugSynonymsArms
BrigatinibAlunbrig, AP 26113, AP-26113, AP26113Treatment (brigatinib, LCT)

Purpose

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. 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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. 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:

      I. 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:

      I. 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. Courses 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.
    

Trial Arms

NameTypeDescriptionInterventions
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. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Brigatinib

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed diagnosis of stage IV non-small cell lung
             cancer (NSCLC) (or recurrent NSCLC not a candidate for definitive multimodality
             therapy)

          -  Documented ALK re-arrangement as detected by: (1) Fluorescence in situ hybridization
             (FISH), (2) immunohistochemistry (IHC), (3) tissue next generation sequencing (NGS),
             or (4) cfDNA NGS

          -  Subjects can be enrolled as (1) tyrosine kinase inhibitor (TKI) naive or (2) after =<
             8 weeks of first-line brigatinib treatment without disease progression

          -  Measurable disease according to RECIST 1.1. At least one lesion of at least 1.0 cm in
             the long-axis diameter for a non-lymph node or at least 1.5 cm in the short-axis
             diameter for a lymph node which is serially measurable according to RECIST 1.1. If
             there is only one target lesion and it is a non-lymph node, it should have a longest
             diameter of at least 1.5 cm

          -  Candidate for local consolidative therapy to at least one site of residual disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L or at least 1500/cubic millimeters or
             at least 1.5 x 10^9/L

          -  Platelet count at least 75,000/cubic millimeters or at least 75 x 10^9/L

          -  Hemoglobin (Hb) at least 9 g/dL (or 5.69 mmol/L) at baseline

          -  Serum creatinine =< 1.5 x upper limit of normal (ULN) or >= 60 mL/minute for subjects
             with creatinine levels > 1.5 x the institutional ULN

          -  Serum total bilirubin less than or equal to =<1.5 x ULN or direct bilirubin =< ULN or
             direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN
             except for subjects with liver metastases (mets) for whom ALT and AST should be =< 5 x
             ULN

          -  International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x 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 x 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: a.) Are postmenopausal for at least 1 year before the screening
             visit, OR b.) Are surgically sterile, OR c.) If they are of childbearing potential,
             agree to practice 2 effective methods of contraception, at the same time, 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: a.)
             Agree to practice effective barrier contraception during the entire study treatment
             period and through 4 months after the last dose of study drug, or b.) Agree to
             completely abstain from heterosexual intercourse

          -  Have normal QT interval on screening electrocardiography (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

        Exclusion Criteria:

          -  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

          -  Symptomatic central nervous system (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: a.) Myocardial infarction (MI) within 6 months prior
             to the first dose of study drug b.) Unstable angina within 6 months prior to first
             dose of study drug c.) Decompensated congestive heart failure (CHF) within 6 months
             prior to first dose of study drug d.) History of clinically significant atrial
             arrhythmia (including clinically significant bradyarrhythmia), as determined by the
             treating physician e.) Any history of ventricular arrhythmia f.) 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 2 years
Safety Issue:
Description:Toxicity data will be summarized using frequency tables. Associations between the types and severity of toxicity and treatment will be evaluated as well.

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:From the date of brigatinib treatment initiation until disease progression or death, assessed up to 2 years
Safety Issue:
Description:The median PFS will be calculated and presented with 2-sided 80% confidence interval (CI). Kaplan-Meier survival probabilities will be plotted over time.
Measure:Overall survival (OS)
Time Frame:From the date of brigatinib treatment initiation until date of death from any cause, assessed up to 2 years
Safety Issue:
Description:The median OS will be calculated and presented with 2-sided 80% CI. Kaplan-Meier survival probabilities will be plotted over time.
Measure:Time to progression of non-local consolidative therapy (LCT) lesion
Time Frame:From the date of brigatinib treatment initiation until progression of a baseline lesion not treated with radiation or surgery, assessed up to 2 years
Safety Issue:
Description: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.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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