Non-Small Cell Lung Cancer (phase 3b/4) MedDRA version: 9.1 Level: LLT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB MedDRA version: 9.1 Level: LLT Classification code 10029522 Term: Non-small cell lung cancer stage IV
Conditions
Sponsors
ArQule Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each patient must meet the following criteria to be enrolled in this study: 1. Provide signed and dated informed consent prior to study-specific screening procedures 2. = 18 years old 3. Histologically or cytologically confirmed inoperable locally advanced or metastatic (stage IIIB/IV) NSCLC 4. = one prior chemotherapy regimen (including adjuvant chemotherapy)(not to have included erlotinib or other EGFR inhibiting agent) 5. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (see Appendix 2) 7. Male or female patients 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 8. Females of childbearing potential must have a negative serum pregnancy test 9. Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 × upper limit of normal (ULN) 10. Total bilirubin = 1.5 × ULN 11. Serum creatinine = 1.5 × ULN 12. Absolute neutrophil count (ANC) = 1.5 x 109/L 13. Platelets = 100 x 109/L 14. Confirmed availability of archival pathology samples (10 unstained paraffinembedded slides) or tissue block suitable for subsequent analysis of K-ras, EGFR, and c-Met Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from the study: 1. Previous receipt of erlotinib or other EGFR inhibiting therapy 2. Receipt of any anti-tumor treatment for NSCLC within 4 weeks (2 weeks for radiotherapy) prior to the start of designated treatment 3. Documented major surgical procedure within 4 weeks prior to randomization. 4. Symptomatic central nervous system metastases either considered in the opinion of investigator to be clinically unstable or which require steroids, anti-epileptics, or other symptom-relieving medications 5. Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives or avoidance of pregnancy measures 6. Significant gastrointestinal disorder that, in opinion of Investigator, could interfere with the absorption of ARQ 197 and/or erlotinib (e.g. Crohn’s disease, small or large bowel resection, malabsorbtion syndrome) 7. Unable or unwilling to swallow the complete dose of erlotinib or ARQ 197 8. Any known contraindication to treatment with ARQ 197 or erlotinib 9. Any known hypersensitivity to any of component of ARQ 197 or erlotinib 10. Other malignancy within 5 years of randomization, with the exception of adequately treated intraepithelial carcinoma of the cervix uteri, prostate carcinoma with a PSA value < 0.2 ng/ml or basal or squamous cell carcinoma of the skin 11. Previously diagnosed grade 3 or 4 (CTCAE) bradycardia or other heart arrhythmia 12. Any other significant co-mormid condition that, in opinion of the Investigator, would impair study participation or cooperation 13. Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate progression-free survival (PFS) among all eligible patients (ITT population) treated with erlotinib plus ARQ 197 compared to erlotinib plus placebo;Secondary Objective: The below mentioned secondary objectives evaluation will be done for all valuable patients and additionally for patients subpopulations characterized by presence or absence k-ras mutations, EGFR associated tumors and c-Met overexpressions at the different combinations. All patients subpopulations will be compared for data regarding patients treated with ARQ 197 + erlotinib compared with patient treated placebo + erlotinib. - progression free survival (PFS) for IIT and subpopulations - overall survival (OS) for IIT and subpopulations - objective response rate (ORR) for IIT and subpopulations - objective response rate (ORR) for IIT patients treated with erlotinib plus placebo following the event of progression on-study and subsequent unblinded cross-over to receive open-label erlotinib plus ARQ 197. - further characterize the safety of ARQ 197 in combination with erlotinib.;Primary end point(s): Progression of the disease | — |
Countries
Germany, Latvia
Outcome results
None listed