Clinical Trials /

Phase 2 Study of Brigatinib in Japanese Patients With ALK-Positive Non-Small Cell Lung Cancer (NSCLC)

NCT03410108

Description:

The purpose of this study is to evaluate efficacy and safety of Brigatinib in Japanese patients with anaplastic lymphoma kinase (ALK)-positive NSCLC.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Study of Brigatinib in Japanese Patients With ALK-Positive Non-Small Cell Lung Cancer (NSCLC)
  • Official Title: A Single-Arm, Multicenter, Phase 2 Study of Brigatinib in Japanese Patients With ALK-Positive Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: Brigatinib-2001
  • SECONDARY ID: U1111-1204-8752
  • NCT ID: NCT03410108

Conditions

  • ALK-positive Advanced NSCLC

Interventions

DrugSynonymsArms
BrigatinibBrigatinib 90 mg + Brigatinib 180 mg

Purpose

The purpose of this study is to evaluate efficacy and safety of Brigatinib in Japanese patients with anaplastic lymphoma kinase (ALK)-positive NSCLC that has progressed after 1 or 2 lines of prior ALK inhibitor therapy.

Detailed Description

      The drug being tested in this study is called Brigatinib. Brigatinib is being tested in
      patients with ALK-positive NSCLC in order to evaluate efficacy and safety of oral doses of
      Brigatinib in Japanese patients with ALK-positive NSCLC.

      The study will enroll approximately 80 participants. Participants will be enrolled in
      non-randomized and opened manner:

      - Brigatinib 90 mg for the first 7 days, followed by Brigatinib 180 mg of Brigatinib tablets,
      once daily in a 28-days cycle.

      All participants will be asked to take tablets of Brigatinib once daily with or without food
      throughout the study.

      This multi-center trial will be conducted in Japan. The overall time to participate in this
      study is approximately 41 months. Participants will make multiple visits to the clinic during
      the treatment period, and posttreatment period including a follow-up assessment after last
      dose of study drug.
    

Trial Arms

NameTypeDescriptionInterventions
Brigatinib 90 mg + Brigatinib 180 mgExperimental90 mg of Brigatinib tablets, once daily for 7 days, followed by 180 mg of Brigatinib tablets, once daily in a 28-days cycle.
  • Brigatinib

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female Japanese patients aged >=20 years on the day of consent.

          2. Voluntary written consent must be given before performance of any study-related
             procedure not part of standard medical care, with the understanding that consent may
             be withdrawn by the patient at any time without prejudice to future medical care.

          3. Have histologically or cytologically confirmed stage IIIB, stage IIIC (locally
             advanced or recurrent and not a candidate for definitive multimodality therapy), or
             stage IV NSCLC.

          4. Must meet 1 of the following 2 criteria:

               1. Have documentation of ALK rearrangement by a positive result from the Vysis ALK
                  Break Apart FISH [fluorescence in situ hybridization] Probe Kit, the Nichirei
                  Histofine ALK iAEP Kit, or the Ventana ALK (D5F3) CDx Assay at any time during
                  prior disease course.

               2. Had a documented ALK rearrangement by a different test at any time during prior
                  disease course, and adequate tissue available for central laboratory testing by
                  the Vysis ALK Break Apart FISH test. Central confirmation of ALK rearrangement is
                  not required before enrollment.

          5. The expansion part only: had documented progressive disease (PD) during treatment or
             within 30 days after treatment with ALK inhibitor.

               -  Note 1: The expansion part consists of the main cohort and a subcohort based on
                  prior ALK inhibitor treatment. The main cohort includes patients who had
                  previously received alectinib (as their only ALK inhibitor) or both crizotinib
                  and alectinib (regardless the sequence of those 2 ALK inhibitors), and a total of
                  47 patients will be enrolled. Patients with all other sequences of up to 2 prior
                  ALK inhibitor(s) may be included in the subcohort, and the number of patients
                  will be limited to 20.

               -  Note 2: Patients who will be included in the main cohort should have documented
                  PD during treatment or within 30 days after treatment with alectinib.

          6. Have at least 1 measurable (ie, target) lesion per RECIST version 1.1. Note:
             Previously irradiated lesions may not be used for target lesions, unless there is
             unambiguous radiological progression after radiotherapy. Brain lesions may not be used
             as target lesions if they were 1) previously treated with whole brain radiation
             therapy (WBRT) within 3 months, or 2) previously treated by stereotactic radiosurgery
             (SRS) or surgical resection.

          7. Recovered from toxicities related to prior anticancer therapy to National Cancer
             Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03
             Grade =<1. Note: Treatment-related alopecia is allowed.

          8. Have a life expectancy of >=3 months.

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

               1. Both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =<2.5
                  times the upper limit of the normal range (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. Serum creatinine <1.5×ULN. For patients with creatinine levels above or equal to
                  1.5×ULN, the patient is eligible if the estimated creatinine clearance using the
                  Cockcroft-Gault formula is ≥30 mL/minute.

               4. Serum lipase =<1.5×ULN and serum amylase =<1.5×ULN.

               5. Absolute neutrophil count (ANC) >=1.5×10^9/L.

               6. Platelet count >=75×10^9/L.

               7. Hemoglobin >=9 g/dL.

         10. Have an Eastern Cooperative Oncology Group (ECOG) performance status of =<2.

         11. Must meet the following criteria:

               1. 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 practice 1 highly effective
                       method of contraception and 1 additional effective (barrier) method 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 practice true abstinence, when this is in line with the preferred
                       and usual lifestyle of the patient, from the time of signing the informed
                       consent through 4 months after that last dose of study drug. (Periodic
                       abstinence [eg, 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.)

               2. Male patients, even if surgically sterilized (ie, status postvasectomy), 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 practice true abstinence, when this is in line with the preferred
                       and usual lifestyle of the patient, during the entire study treatment period
                       and through 4 months after that last dose of study drug. (Periodic
                       abstinence [eg, 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.)

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

        Exclusion Criteria:

          1. Expansion part only: received any prior not specified ALK inhibitor.

          2. Expansion part only: received more than 2 prior ALK inhibitors. Note: The safety
             evaluation lead-in part allows patients with any line of prior ALK inhibitor which
             includes treatment-naïve patients; however, ALK inhibitor-naïve patients may be
             enrolled after the confirmation of first 3 DLT evaluable patients to have no more than
             1 DLT during Cycle 1 by investigator's judgement.

          3. Received ALK inhibitor within 7 days before the first dose of Brigatinib.

          4. Previously received more than 1 regimen (more than 3 regimens in the safety evaluation
             lead-in part) of systemic anticancer therapy (not specified ALK inhibitor) for locally
             advanced or metastatic disease. Note: A systemic anticancer therapy regimen will be
             counted if it is administered over at least 1 cycle. A new anticancer agent used as
             maintenance therapy will be counted as a new regimen unless it was previously used as
             initial anticancer therapy. Neoadjuvant or adjuvant systemic anticancer therapy will
             be counted as a prior regimen if completion of (neo) adjuvant therapy occurred <12
             months before the first dose of Brigatinib.

          5. Treatment with any investigational products except for specified ALK inhibitor within
             30 days or 5 half-lives of that investigational agent, whichever is longer, before the
             first dose of Brigatinib.

          6. Received chemotherapy or radiation within 14 days before the first dose of Brigatinib,
             except SRS or stereotactic body radiation therapy.

          7. Received antineoplastic monoclonal antibodies within 30 days before the first dose of
             Brigatinib.

          8. Received systemic treatment with strong inhibitors or strong and moderate inducers of
             cytochrome P450 (CYP) 3A within 7 days before the first dose of Brigatinib.

          9. Had major surgery within 30 days before the first dose of Brigatinib. Minor surgical
             procedures such as venous catheter placement or minimally invasive biopsies are
             allowed.

         10. Have been diagnosed with another primary malignancy other than NSCLC, except for the
             following adequately/definitively treated malignancies: nonmelanoma skin cancer,
             cervical cancer in situ, nonmetastatic prostate cancer; or patients with another
             primary malignancy who are definitively relapse-free with at least 3 years elapsed
             since the diagnosis of the other primary malignancy.

         11. Have symptomatic central nervous system (CNS) metastases (parenchymal or
             leptomeningeal) at screening or asymptomatic disease requiring an increasing dose of
             corticosteroids to control symptoms within 7 days before the first dose of Brigatinib.
             Note: If a patient has worsening neurological symptoms or signs due to CNS metastasis,
             the patient needs to complete local therapy and be neurologically stable (with no
             requirement for an increasing dose of corticosteroids or use of anticonvulsants for
             symptomatic control) for 7 days before the first dose of Brigatinib.

         12. Have current spinal cord compression (symptomatic or asymptomatic and detected by
             radiographic imaging). Patients with asymptomatic leptomeningeal disease and without
             cord compression are allowed.

         13. Have ongoing or history of interstitial lung disease (ILD) (including interstitial
             pneumonitis, pneumonitis, radiation pneumonitis, drug-related pneumonitis, organized
             pneumonia, and pulmonary alveolitis).

         14. Have significant, uncontrolled, or active cardiovascular disease, specifically
             including, but not limited to:

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

               2. Unstable angina within 6 months before the first dose of Brigatinib.

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

               4. Uncontrolled atrial arrhythmias despite appropriate medical therapy.

               5. History of ventricular arrhythmia, including history of ventricular tachycardia,
                  ventricular fibrillation, or torsades de pointes. Patients with premature
                  ventricular contractions are allowed.

               6. Cerebrovascular accident or transient ischemic attack within 6 months before the
                  first dose of Brigatinib.

               7. Resting heart rate <60 bpm.

         15. Have uncontrolled hypertension. Patients with hypertension should be under treatment
             at the start of screening and demonstrate adequate control of blood pressure.

         16. Have an ongoing or active infection, including, but not limited to, the requirement
             for intravenous antibiotics.

         17. Have a known history of HIV infection. Testing is not required in the absence of
             history.

         18. Hepatitis B surface antigen (HBsAg) positive, detectable hepatitis B viral load, or
             detectable hepatitis C virus (HCV) infection viral load. Note: Patients who have
             positive hepatitis B core antibody (HBcAb) or hepatitis B surface antibody (HBsAb) can
             be enrolled but must have an undetectable hepatitis B viral load. Patients who have
             positive HCV antibody can be enrolled but must have an undetectable hepatitis C viral
             load.

         19. Have malabsorption syndrome or other gastrointestinal illness that could affect oral
             absorption of Brigatinib.

         20. Have a known or suspected hypersensitivity to Brigatinib or its excipients.

         21. Female patients who are lactating and breastfeeding or have a positive serum pregnancy
             test during the screening period.

         22. Have any condition or illness that, in the opinion of the investigator, would
             compromise patient safety or interfere with the evaluation of Brigatinib.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed Objective Response Rate (ORR) in the Main Cohort of the Expansion Part
Time Frame:Up to 23 months
Safety Issue:
Description:ORR is defined the percentage of the participants who are confirmed to have achieved complete response (CR) or partial response (PR) per an Independent Review Committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 after the initiation of study treatment.

Secondary Outcome Measures

Measure:Confirmed ORR in the Overall Population of the Expansion Part
Time Frame:Up to 41 months
Safety Issue:
Description:
Measure:Duration of Response (DOR) in the Main Cohort and in the Overall Population of the Expansion Part
Time Frame:Up to 41 months
Safety Issue:
Description:DOR will be assessed by an IRC, per RECIST version 1.1. DOR is defined as the time between the first documentation of objective tumor response (CR or PR) and the first subsequent documentation of objective progressive disease (PD) or death due to any cause, whichever occurs first.
Measure:Progression-Free Survival (PFS) in the Main Cohort and in the Overall Population of the Expansion Part
Time Frame:Up to 41 months
Safety Issue:
Description:PFS will be assessed by an IRC, per RECIST version 1.1. PFS is defined as the time from the start of study treatment to the first documentation of objective PD or to death due to any cause, whichever occurs first.
Measure:Disease Control Rate (DCR) in the Main Cohort and in the Overall Population of the Expansion Part
Time Frame:Up to 41 months
Safety Issue:
Description:DCR will be assessed by an IRC, per RECIST version 1.1. DCR is defined as the percentage of participants who are confirmed to have achieved CR or PR or have a best overall response of stable disease (SD), per RECIST version 1.1, for 6 weeks or more after initiation of study drug.
Measure:Time to Response in the Main Cohort and in the Overall Population of the Expansion Part
Time Frame:Up to 41 months
Safety Issue:
Description:Time to response will be assessed by an IRC, per RECIST version 1.1. Time to response is defined as the time interval from the date of the first dose of study treatment until the initial observation of CR or PR for patients with confirmed CR/PR.
Measure:Overall Survival (OS) in the Main Cohort and in the Overall Population of the Expansion Part
Time Frame:Up to 41 months
Safety Issue:
Description:OS is the time from the start of study treatment to the date of death.
Measure:Central Nervous System (CNS) Response in the Main Cohort and in the Overall Population of the Expansion Part
Time Frame:Up to 41 months
Safety Issue:
Description:CNS response will be assessed by an IRC, per modified RECIST version 1.1 for assessment of intracranial efficacy. CNS response is defined as the percentage of the participants who have achieved CR or PR in the intracranial CNS per modified RECIST version 1.1 as evaluated by an IRC after the initiation of study treatment.
Measure:Time on Treatment in the Main Cohort and in the Overall Population of the Expansion Part
Time Frame:Up to 41 months
Safety Issue:
Description:Time on treatment is the time interval from the first dose to the last dose of Brigatinib.
Measure:Confirmed ORR in the Main Cohort of the Expansion Part
Time Frame:Up to 41 months
Safety Issue:
Description:The percentage of participants who are confirmed to have achieved CR or PR per investigator using RECIST version 1.1 after the initiation of study treatment.
Measure:Patient-Reported Outcomes (PROs) of Health-Related Quality of Life (HRQOL) Scores and Symptoms of Lung Cancer in the Main Cohort of the Expansion Part
Time Frame:Up to 41 months
Safety Issue:
Description:PROs of HRQOL scores and symptoms of lung cancer, assessed with European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, its lung cancer module QLQ-LC13, and the 5-level version of EuroQol 5-dimensional questionnaire (EQ-5D-5L) which are related to patient health, symptoms, and problems. Participants will answer for these questionalries. EORTC-QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). QLQ-LC13 contains 13 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]). EQ-5D-5L consists of 25 checklists on 5 dimensions (Mobility, Self-care, Usual activities, Pain/Discomfort, and Anxiety/Depression) and EQ VAS. EQ VAS records the respondent's self-rated health on a 20 cm, vertical, visual analogue scale ranging from 0 [worst] to 100 [best].
Measure:Cmax: Maximum Observed Plasma Concentration for Brigatinib on Cycle 1 Days 1 and 22
Time Frame:Pre-dose and at multiple time points (0.5, 1, 2, 4, 6, 8, 12, 24; up to 24 hrs) post-dose of Cycle 1 Days 1 and 22
Safety Issue:
Description:
Measure:tmax: Time of First Occurrence of Cmax for Brigatinib on Cycle 1 Days 1 and 22
Time Frame:Pre-dose and at multiple time points (0.5, 1, 2, 4, 6, 8, 12, 24; up to 24 hrs) post-dose of Cycle 1 Days 1 and 22
Safety Issue:
Description:
Measure:AUC: Area under the Plasma Concentration-Time Curve for Brigatinib on Cycle 1 Days 1 and 22
Time Frame:Pre-dose and at multiple time points (0.5, 1, 2, 4, 6, 8, 12, 24; up to 24 hrs) post-dose of Cycle 1 Days 1 and 22
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Takeda

Last Updated

March 29, 2018