Clinical Trials /

Brigatinib in ALK-positive NSCLC Identified Via Blood-based Assays

NCT04074993

Description:

This is single-arm, open-label study design. Patients will receive brigatinib until disease progression, unacceptable toxicity, withdrawal of consent, of death.

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

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Brigatinib in ALK-positive NSCLC Identified Via Blood-based Assays
  • Official Title: Brigatinib in ALK-positive NSCLC Identified Via Blood-based Assays

Clinical Trial IDs

  • ORG STUDY ID: NCC2019-0212
  • NCT ID: NCT04074993

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
BrigatinibBrigatinib

Purpose

This is single-arm, open-label study design. Patients will receive brigatinib until disease progression, unacceptable toxicity, withdrawal of consent, of death.

Detailed Description

      Based on the clinical efficacy of ALK inhibitors in ALK+NSCLC, NCCN guidelines recommend ALK
      molecular testing of lung cancer patients, to select patients for ALK-targeted therapy.
      However, molecular testing via tissue biopsy cannot always be performed on NSCLC patients,
      potentially limiting access of effective treatment to the subset of patients who are able to
      undergo current testing procedures that utilize tissue biopsies. Obtaining an adequate tissue
      biopsy specimen for NSCLC presents a number of challenges. In particular, the method for
      diagnosis of lung cancer depends on the location, size, and type of suspected lung cancer,
      and the presence or absence of metastases. Common procedures for centrally located tumors
      include bronchoscopy and sputum cytology, which frequently yield insufficient tumor tissue
      for comprehensive mutation testing. In addition, 75% of patients are diagnosed with
      late-stage disease and often present with multiple comorbidities. Biopsies in these patients
      can lead to complications such as pneumothorax, hemoptysis, other bleeding complications, and
      cardiopulmonary decompensation. As a result of these factors, a physician treating a patient
      who presents with a significant burden of disease as well as significant comorbidities may
      rightly consider whether it is in the best interest of the patient to undergo a risky and
      potentially unsuccessful procedure. Thus, there exists a major unmet clinical need for
      testing procedures that do not require tumor tissue. The purpose of this phase II study is to
      assess the efficacy of brigatinib in patients with advanced NSCLC harboring ALK rearrangement
      that are selected using predictive biomarkers identified via blood-based assays.
    

Trial Arms

NameTypeDescriptionInterventions
BrigatinibExperimentalSubject will be treated with Brigatinib 90mg/day for 1 week and then 180mg/day PO daily. A Cycle will be defined as 28-days. Treatment will be continued until disease progression or unacceptable toxicity.
  • Brigatinib

Eligibility Criteria

        Inclusion Criteria:

          1. The participant(or legally acceptable representative if applicable) provides written
             informed consent for the study

          2. Patients who have disease progression with prior one ALK-TKI treatment for inoperable
             Stage III (locally advanced) or metastatic ALK+ NSCLC.(Previous treatment only allowed
             one ALK-inhibitor) Patients who have received prior neo-adjuvant, adjuvant
             chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for
             non-metastatic disease must have experienced a treatment-free interval of at least 6
             months since the last chemotherapy, radiotherapy, or chemoradiotherapy cycle.

          3. ALK rearrangement , as detected via the blood somatic mutation assay

          4. One prior ALK inhibitor therapy

          5. Have at least 1 measurable lesion per RECIST version 1.1

          6. Have Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          7. Recovered from toxicities related to prior anticancer therapy to NCI CTCAE, version
             5.0, Grade≤1(Note : Alopecia, sensory neuropathy Grade≤2, or other Grade≤2 AEs not
             constituting a safety risk based on Investigator's judgement are acceptable

          8. Have a life expectancy of ≥3 months

          9. Have adequate organ and hematologic function as determined by:

               1. ALT/AST≤2.5×ULN; ≤5×ULN is acceptable if liver metastases are present

               2. Total serum bilirubin≤1.5×ULN (<3.0×ULN for patients with Gilbert syndrome)

               3. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, using the MDRD
                  equation

               4. Absolute neutrophil count ≥1.5×109/L.

               5. Platelet count ≥75×109/L.

               6. Hemoglobin ≥9 g/dL.

               7. Serum lipase ≤1.5×ULN

         10. For female patients of childbearing potential, have a negative pregnancy test(urine or
             serum) documented ≤3 days before start of study medication.

             non-childbearing potential which is defined as :

               -  female patient≥45 years of age and has not had menses for greater than 1 year

               -  a female who is status post hysterectomy, oophorectomy

         11. Female patients of childbearing potential and male patients with partners of
             childbearing potential must agree to use 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
             intercourseHave the willingness and ability to comply with scheduled visit and study
             procedures.

             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

         12. Have the willingness and ability to comply with scheduled visit and study procedures.

         13. Be ≥ 18 years of age

        Exclusion Criteria:

          1. Has received ALK-targeted TKI within 7 days before the first dose of study
             treatment(If clinically justified, 3 days wash-out period could be allowed).

          2. Has received radiotherapy within 14 days before the first dose of study treatment
             except for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy
             (SBRT). A 1-week washout is permitted for palliative radiation(≤2 weeks of
             radiotherapy) to non-CNS disease.

          3. Had major surgery within 28 days of the first dose of study treatment. Minor surgical
             procedures are allowed.

          4. Has symptomatic brain metastasis or leptomeningeal disease. Prior brain metastasis or
             leptomeningeal disease allowed if asymptomatic or stable symptoms that did not require
             an increased dose of corticosteroids to control symptoms within 7 days prior to study
             enrollment. If patients have neurological symptoms or signs due to CNS metastasis,
             patients need to complete whole brain radiation or stereotactic radiosurgery treatment
             before enrollment and be clinically stable.

          5. Has current spinal cord compression

          6. Other malignancy within 3 years, except for adequately treated carcinoma in situ of
             the cervix, basal or squamous cell skin cancer, localized prostate cancer treated
             surgically with curative intent, and ductal carcinoma in situ treated surgically with
             curative intent

          7. Any gastrointestinal (GI) disorder that may affect absorption of oral medications,
             such as malabsorption syndrome or status post-major bowel resection

          8. Have significant, uncontrolled, or active cardiovascular disease, specifically
             including, but not restricted to:

               1. Myocardial infarction within 6 months before the first dose of brigatinib.

               2. Unstable angina within 6 months before first dose of brigatinib.

               3. Congestive heart failure within 6 months before first dose of brigatinib.

               4. History of clinically significant atrial arrhythmia (including clinically
                  significant bradyarrhythmia).

               5. Any history of clinically significant ventricular arrhythmia.

          9. Has uncontrolled hypertension.

         10. Had a cerebrovascular accident or transient ischemic attack within 6 months before
             first dose brigatinib.

         11. Have a history or the presence of pulmonary interstitial disease, drug-related
             pneumonitis, or radiation-related pneumonitis

         12. Active infection requiring systemic therapy.

         13. Known history of HIV infection.

         14. Has a known or suspected hypersensitivity to brigatinib or its excipients.

         15. Female patients who are both lactating and breastfeeding or have a positive serum
             pregnancy test during the screening period or a positive urine pregnancy test on Day 1
             before first dose of study drug (if applicable).

         16. Have any condition or illness that, in the opinion of the investigator, would
             compromise

         17. patient safety or interfere with the evaluation of brigatinib

         18. Received systemic treatment with strong cytochrome P-450 (CYP)3A inhibitors, strong
             CYP3A inducers, or moderate CYP3A inducers within 14 days before enrollment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate
Time Frame:From Cycle1 Day 1 until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months. Tumor assessment will be performed at the end of cycle 2(every 2 cycles, each cycle is 28 days).
Safety Issue:
Description:Objective response rate

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ji-youn Han

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