tivantinib plus erlotinib versus placebo plus erlotinib for the treatment of non-squamous, non-small-cell lung cancer

Conditions: Non Squamous, Non-small-cell Lung Cancer

Summary: this study is to determine if the combination regimen of tivantinib with erlotinib will improve overall survival relative to erlotinib alone in subjects with locally advanced or metastatic non-squamous, non-small cell lung cancer who have received 1 or 2 prior systemic anti-cancer therapies.


Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed surgically unresectable locally advanced or metastatic (stage iiib/iv) non-squamous non-small-cell lung cancer. * measurable disease and documented disease progression following last prior therapy according to response evaluation criteria in solid tumors (recist) criteria, version 1.1. * have received one or two prior lines of systemic anti-cancer therapy therapy for advanced or metastatic disease, one of which must be a platinum-doublet therapy. patients who received only adjuvant treatment will be eligible only if disease progression occurred \<6 months after completion of adjuvant therapy. prior maintenance therapy is allowed and will be considered as the same line of therapy when continued without discontinuation after initiation of a treatment regimen. * eastern cooperative oncology group (ecog) performance status of 0 or 1 * resolution of any toxic effects of prior therapy (including radiotherapy) according to national cancer institute (nci) common terminology criteria for adverse events (ctcae), version 4.0, grade ≤1 (with the exception of alopecia and ≤grade 2 neuropathy). subject must have recovered from significant surgery-related complications. * demonstrate adequate bone marrow, liver, and renal functions, defined as: * alt, ast, and alkaline phosphatase ≤ 2.5 × upper limit of normal (uln) in subjects with no liver metastasis and ≤5.0 x uln in subjects with liver metastasis. * total bilirubin ≤ 1.5 × uln (≤ 4 × uln total and ≤1.5 × uln direct bilirubin is acceptable for subjects with gilbert's syndrome). * anc ≥1.5 × 10\^9/l. * platelet count ≥100 × 10\^9/l. * hemoglobin ≥9.0 g/dl (transfusion and/or growth factor support allowed). * serum creatinine ≤1.5 × uln or creatinine clearance ≥ 60 ml/min. * archival and/or fresh biopsy tissue sample must be available for biomarker determination. the status of the following biomarkers will be collected in this study: egfr and kras mutation status prior to randomization, and met status post randomization * if of child-bearing/reproductive potential (female or male), must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received * if female and of childbearing potential, must have a negative result of a pregnancy test (serum or urine) within 72 hours prior to initiating study treatment. * must have signed and dated an approved informed consent form (including hipaa authorization, if applicable) before performance of any study-specific procedures or tests. subjects must be fully informed about their illness and the investigational nature of the study protocol (including forseeable risks and possible side effects) exclusion criteria: * prior therapy with an egfr inhibitor and/or arq 197 (or other known c-met inhibitor). * receipt of any systemic anti-tumor treatment for nsclc within 3 weeks prior to randomization. * receipt of palliative radiotherapy within 2 weeks or radiotherapy for curative intent of target lesions within 3 weeks prior to randomization. lesions subjected to radiotherapy within 3 weeks prior to randomization may not be used as target lesions. * major surgical procedure within 3 weeks prior to randomization. * 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 symptomatic bradycardia (subjects with asymptomatic bradycardia and heart rate above 50 bpm are allowed) or other cardiac arrhythmia defined as ≥grade 2 according to nci 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). * clinically unstable central nervous system (cns) metastasis (to be enrolled in the study, subjects must have confirmation of stable disease by mri or computed tomography (ct) scan within 4 weeks of randomization and have cns metastases well controlled by steroids, anti-epileptics or other symptom-relieving medications). * need to breastfeed a child during or within 12 weeks of completing the study. * significant gastrointestinal disorder that, in the opinion of the investigator, could interfere with absorption of arq 197 and/or erlotinib (eg, crohn's disease, small or large bowel resection, malabsorption syndrome). * inability or unwillingness to swallow the complete doses of arq 197 or erlotinib. * any known contraindication to treatment with, including hypersensitivity to, arq 197 or erlotinib. * history of malignancy other than nsclc within the 5 years prior to randomization, with the exceptions of adequately treated intraepithelial carcinoma of the cervix uteri; prostate carcinoma with a prostate-specific antigen value \<0.2 ng/ml; or basal or squamous-cell carcinoma of the skin. * known infection with human immunodeficiency virus (hiv), hepatitis b virus (hbv) or hepatitis c virus (hcv). * any other significant co-morbid condition that, in opinion of the investigator, would impair study participation or cooperation.

Keywords: non squamous, non-small-cell lung cancer epidermal growth factor receptor c-met inhibitor