Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Condition: Metastatic Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: ARQ 197 plus erlotinib; Pemetrexed, docetaxel or gemcitabine
Intervention description: Eligible subjects will be randomly assigned to receive erlotinib plus ARQ 197.; Investigator's choice of a single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered according to the approved label.
Intervention MeSH terms: Gemcitabine; Docetaxel; Pemetrexed; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 96.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: KRAS mutation; metastatic NSCLC

Summary:

      The purpose of this study is to evaluate progression-free survival among subjects with KRAS
      mutation positive Non-Small Cell Lung Cancer (NSCLC) treated with erlotinib plus tivantinib
      (ARQ 197) compared to single agent chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provide signed and dated informed consent prior to study-specific screening procedures

          2. Male or female at least 18 years of age

          3. Histologically or cytologically confirmed inoperable locally advanced or metastatic
             (stage IVA/IVB) NSCLC

          4. Documented KRAS mutation positive status (per Lung Cancer Mutation Consortium [LCMC]
             guidelines; see www.golcmc.com)

          5. At least one prior chemotherapy regimen for advanced NSCLC

          6. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
             criteria, Version 1.1

          7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

          8. Male or female subjects of child-producing potential must agree to use double barrier
             contraception, oral contraceptives or avoidance of pregnancy measures during the study
             and for 90 days after the last day of treatment

          9. Females of childbearing potential must have a negative serum pregnancy test

         10. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × upper limit of
             normal (ULN) or ≤ 5 × ULN with metastatic liver disease

         11. Total bilirubin ≤ 1.5 × ULN

         12. Serum creatinine ≤ 1.5 × ULN

         13. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

         14. Platelets ≥ 100 x 10^9/L

         15. Hemoglobin ≥ 10 g/dL (transfusion is allowed at least 7 days prior to randomization)

         16. Subjects must agree to allow testing for c-Met status if archival and/or fresh tissue
             biopsy samples are available.

        Exclusion Criteria:

          1. Previous receipt of erlotinib or other epidermal growth factor receptor (EGFR)
             inhibitors

          2. Previous receipt of any c-MET inhibitor (a receptor tyrosine kinase) or other
             c-MET-targeted therapy, including ARQ 197, MetMab, crizotinib

          3. Prior receipt of chemotherapy agent selected for administration in this study (e.g.,
             if subject was treated with gemcitabine, he is not eligible to receive gemcitabine in
             this study but eligible to receive pemetrexed or docetaxel).

          4. Inability or unwillingness to receive ARQ 197, erlotinib, docetaxel, gemcitabine,
             and/or pemetrexed including contraindications, hypersensitivity, or prior
             administration

          5. Receipt of any anti-tumor treatment for NSCLC within 3 weeks (2 weeks for
             radiotherapy) prior to randomization

          6. Pregnant or breastfeeding

          7. Significant gastrointestinal disorder that could, in the opinion of the Investigator,
             interfere with the absorption of ARQ 197 and/or erlotinib

          8. Any other significant co-morbid conditions that in the opinion of the Investigator
             would impair study participation or cooperation

          9. Other malignancies within the last three years, with the exception of adequately
             treated intraepithelial carcinoma of the cervix uteri, prostate carcinoma with a
             prostate-specific antigen (PSA) value < 0.2 ng/mL or basal or squamous cell carcinoma
             of the skin

         10. Known human immunodeficiency virus (HIV), or active hepatitis B virus (HBV) or
             hepatitis C virus (HCV) infection

         11. Major surgical procedure within 4 weeks prior to randomization

         12. History of cardiac disease: Congestive heart failure defined as Class II to IV per New
             York Heart Association classification; Active coronary artery disease; Previously
             diagnosed bradycardia or other cardiac arrhythmia defined as ≥ Grade 2 according to
             National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
             (CTCAE), version 4.0, or uncontrolled hypertension; Myocardial infarction that
             occurred within 6 months prior to study entry (myocardial infarction that occurred > 6
             months prior to study entry is permitted)

         13. Clinically unstable central nervous system metastasis (to be enrolled in the study,
             subjects must have confirmation of stable disease by MRI or CT scan within 4 weeks of
             randomization and have central nervous system [CNS] metastases well controlled by
             steroids, anti-epileptics or other symptom-relieving medications)

         14. Known EGFR-mutation positive status