A Randomized Phase 2 Study of Erlotinib + ARQ 197 Versus Erlotinib + Placebo in Previously Treated Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This is a randomized, placebo-controlled, double blind phase 2 study designed to compare treatment with ARQ 197 plus erlotinib to erlotinib plus placebo in patients with non-small cell lung cancer. The study will enroll patients who have had one prior chemotherapy regimen (other than erlotinib) for NSCLC.

Detailed Description
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This is a randomized, placebo-controlled, double blind phase 2 study designed to compare treatment with ARQ 197 plus erlotinib to erlotinib plus placebo in patients with non-small cell lung cancer. The study will enroll patients who have had one prior chemotherapy regimen (other than erlotinib) for NSCLC. The study will evaluate progression-free survival between the two arms. A total of 154 patients will be enrolled.

Official Title
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A Randomized Phase 2 Study of Erlotinib Plus ARQ 197 Versus Erlotinib Plus Placebo in Previously Treated Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: ARQ 197
* Drug: Erlotinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide signed and dated informed consent prior to study-specific screening procedures ≥ 18 years old Histologically or cytologically confirmed inoperable locally advanced or metastatic (stage IIIB/IV) NSCLC ≥ one prior chemotherapy regimen (including adjuvant chemotherapy)(not to have included erlotinib or other EGFR inhibiting agent) Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 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 Females of childbearing potential must have a negative serum pregnancy test Good organ function Confirmed availability of archival pathology samples (10 unstained paraffin-embedded slides) or tissue block suitable for subsequent analysis of KRAS, EGFR, and c-Met Exclusion Criteria: Previous receipt of erlotinib or other EGFR inhibiting therapy Receipt of any anti-tumor treatment for NSCLC within 4 weeks (2 weeks for radiotherapy) prior to the start of designated treatment Documented major surgical procedure within 4 weeks prior to randomization. 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 Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives or avoidance of pregnancy measures 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) Unable or unwilling to swallow the complete dose of erlotinib or ARQ 197 Any known contraindication to treatment with ARQ 197 or erlotinib Any known hypersensitivity to any of component of ARQ 197 or erlotinib 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 Previously diagnosed grade 3 or 4 (CTCAE) bradycardia or other heart arrhythmia Any other significant co-mormid condition that, in opinion of the Investigator, would impair study participation or cooperation Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Erlotinib (150 mg) once daily plus ARQ 197 (360 mg) twice daily. | Drug: ARQ 197<br>* 360 mg administered twice daily until disease progression, unacceptable toxicity or other discontinuation criterion is met<br>* Other names: Tivantinib;Drug: Erlotinib<br>* Erlotinib is a white, film coated tablet in strengths of 25, 100 and 150 mg administered once daily until disease progression, unacceptable toxicity or other discontinuation criterion is met.<br>* Other names: Tarceva;|
| Active Comparator: 2<br>Erlotinib (150 mg) once daily plus ARQ 197 placebo twice daily | Drug: Erlotinib<br>* Erlotinib is a white, film coated tablet in strengths of 25, 100 and 150 mg administered once daily until disease progression, unacceptable toxicity or other discontinuation criterion is met.<br>* Other names: Tarceva;Drug: Placebo<br>* The placebo is provided as a capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate progression free survival (PFS) in patients treated with erlotinib plus ARQ 197 versus erlotinib plus placebo |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate overall survival (OS) |  |  | 
| Overall response rate (ORR) |  |  | 
| Safety of ARQ 197 in combination with erlotinib in patients with NSCLC |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC