Clinical Trials /

Trial of Dose Escalated BGB324 in Previously Treated Non-small Cell Lung Cancer.

NCT02922777

Description:

This study is being done to evaluate the safety of the investigational study drug, BGB324 when administered in combination with docetaxel, and to establish the maximum tolerated dose.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Trial of Dose Escalated BGB324 in Previously Treated Non-small Cell Lung Cancer.
  • Official Title: Phase 1 Trial of Dose Escalated BGB324 in Combination With Docetaxel for Previously Treated Advanced Non-small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: STU 052015-077
  • NCT ID: NCT02922777

Conditions

  • Non-Small Cell Lung Carcinoma

Interventions

DrugSynonymsArms
BGB324BGB324 in combination with docetaxel
DocetaxelTaxotereBGB324 in combination with docetaxel

Purpose

This study is being done to evaluate the safety of the investigational study drug, BGB324 when administered in combination with docetaxel, and to establish the maximum tolerated dose.

Detailed Description

      Lung cancer remains the leading cause of cancer-related deaths worldwide with an estimated
      incidence of 1.6 million cases resulting in 1.4 million deaths in annually. Non-small-cell
      lung cancer (NSCLC) represents 80-85% of cases, and adenocarcinoma is the most common
      histology.2 The majority of NSCLC patients present with advanced or metastatic disease that
      is not amenable to surgical resection. Platinum-based combination chemotherapy has reached a
      therapeutic plateau with a median overall survival (OS) of 7.4 to 9.9 months.

      BGB324 is a potent selective small molecule inhibitor of Axl, a surface membrane protein
      kinase receptor that is over-expressed in many metastatic solid tumors and has been
      identified as a marker of a poor prognosis in patients with non-small cell lung cancer
      (NSCLC).
    

Trial Arms

NameTypeDescriptionInterventions
BGB324 in combination with docetaxelExperimentalThe dose of docetaxel will be 75 mg/m2 given IV every 21 days. The dose of BGB324 will be escalated in a standard 3+3 fashion until a maximum tolerated dose is determined.
  • BGB324
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria:

        A patient is eligible for the study if the following criteria are met:

          1. Provision of written informed consent to participate in this investigational study

          2. Histologically or cytologically confirmed advanced (stage 4, according to the
             American Joint Committee on Cancer [AJCC] Staging manual) NSCLC

          3. Up to three previous lines of therapy, of which one must have been a platinum-based
             doublet therapy and no more than two were cytotoxic chemotherapy.

          4. Radiographic disease recurrence or progression during or after the last line of
             chemotherapy

          5. Patients with known activating EGFR mutations or ALK rearrangements should have
             progressed after appropriate targeted treatment in addition to progressing during or
             after platinum-based doublet chemotherapy

          6. European Cooperative Oncology Group (ECOG) performance status 0 or 1

          7. Age 18 years or older

          8. Measurable or evaluable disease according to RECIST v1.1

          9. Previously treated brain metastases (surgery and/or radiation therapy) are eligible,
             provided that patients are asymptomatic and not requiring corticosteroids

         10. The following minimum intervals are required between prior treatment and initiation
             of study therapy:

             Cytotoxic chemotherapy: 3 weeks Molecularly targeted therapy or immunotherapy: 2
             weeks Conventional fractionated radiation therapy: 2 weeks Stereotactic radiation
             therapy: 1 week Major surgery: 3 weeks

         11. Adequate hematologic function (absolute neutrophil count [ANC] ≥ 1500 cells/µL;
             hemoglobin ≥ 9 g/dL; platelets ≥ 100,000/µL

         12. Adequate renal function (serum creatinine ≤ 1.5 mg/dL or calculated creatinine
             clearance ≥ 50 mL/min using the Cockcroft-Gault equation)

         13. Adequate hepatic function: total bilirubin ≤ upper limit of normal [ULN], alanine
             aminotransferase [ALT] ≤ 1.5 x ULN, aspartate aminotransferase [AST] ≤ 1.5 x ULN).
             ALT and AST ≤ 5x ULN if documented liver metastases

         14. Previous treatment-associated toxicities resolved to CTCAE grade ≤2 (except alopecia)

         15. Adequate archival tissue (10-15 slides, or 5 slides with 3 sections per slide) for
             biomarker analysis

         16. Female patients of childbearing potential must have a negative serum pregnancy test
             within 7 days prior to taking their first dose of BGB324. Male patients and female
             patients of reproductive potential must agree to practice highly effective methods of
             contraception (such as hormonal implants, combined oral contraceptives, injectable
             contraceptives, intrauterine device with hormone spirals, total sexual abstinence,
             vasectomy) throughout the study and for ≥3 months after the last dose of BGB324.
             Female patients are considered NOT of childbearing potential if they have a history
             of surgical sterility, including tubal ligation, or evidence of post-menopausal
             status defined as any of the following:

               -  Natural menopause with last menses >1 year ago

               -  Radiation induced oophorectomy with last menses >1 year ago

               -  Chemotherapy induced menopause with last menses >1 year ago

        Exclusion Criteria

        A patient is excluded from the study if any of the following criteria are met:

          1. Pregnant or lactating

          2. Abnormal left ventricular ejection fraction on echocardiography (less than the lower
             limit of normal for a patient of that age at the treating institution or <45%)

          3. History of an ischemic cardiac event including myocardial infarction within 3 months
             of study entry

          4. NSCLC with evidence of a centrally cavitating lesion

          5. Peripheral neuropathy NCI CTCAE ≥Grade 2 at baseline

          6. Pulmonary hemorrhage or hemoptysis > 2.5 mL blood within 6 weeks (or within 2 weeks
             if source definitively treated [eg, radiation therapy or bronchoscopic procedure])

          7. Congestive cardiac failure of >Grade 2 severity according to the NYHA defined as
             symptomatic at less than ordinary levels of activity

          8. Unstable cardiac disease, including unstable angina or unstable hypertension, as
             defined by the need for change in medication for lack of disease control within the
             last three months

          9. History or presence of sustained bradycardia (less than or equal to 60 BPM) or
             history of symptomatic bradycardia, left bundle branch block, cardiac pacemaker or
             significant atrial tachyarrhythmias , as defined by the need for treatment

         10. Previous treatment with docetaxel or an Axl inhibitor

         11. Current treatment with agents that may prolong QT interval and may cause Torsade de
             Points which cannot be discontinued at least five half-lives prior to treatment.
             Please see Appendix J for list of relevant medications

         12. Known family or personal history of long QTc syndrome or ventricular arrhythmias
             including ventricular bigeminy

         13. Previous history of Grade 3 or worse drug-induced QTc prolongation requiring
             treatment withdrawal

         14. Screening 12-lead ECG with a measurable QTc interval according to Fridericia's
             correction >450 ms

         15. Ongoing infection requiring systemic treatment

         16. Inability to tolerate oral medication

         17. Impaired coagulation as evidenced by:

               -  INR >1.5 times ULN, or

               -  aPTT > 1.5 times ULN

         18. Clinically active existing gastrointestinal disease affecting drug absorption, such
             as celiac disease or Crohn's disease

         19. Previous bowel resection anticipated to affect drug absorption

         20. Any evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic
             impairment) or current unstable or uncompensated respiratory or cardiac conditions
             which makes it undesirable for the patient to participate in the study or which could
             jeopardize compliance with the protocol

         21. Treatment with any medication which is predominantly metabolized by CYP3A4 and has a
             narrow therapeutic index

         22. Active, uncontrolled central nervous system (CNS) disease

         23. Known active infection with human immunodeficiency virus (HIV), hepatitis B or C
             viruses (screening not required)

         24. Major surgery within 28 days prior to the start of BGB324, excluding skin biopsies
             and procedures for insertion of central venous access devices
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the maximum tolerated dose of BGB324 in combination with docetaxel
Time Frame:42 days or 2 cycles of 21 days
Safety Issue:
Description:Determine and recommended the Phase 2 dose of BGB324 administered with the standard dose of docetaxel in patients in NSCLC by pharmacodynamics and pharmacokinetic assessments.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Texas Southwestern Medical Center

Last Updated

November 22, 2016