A Study of ARQ 197 in Combination With Erlotinib

Study Overview
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Brief Summary
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This is a phase I study to determine the safety, tolerability and recommended phase II dose of ARQ 197 given in combination with erlotinib as primary endpoints in CYP2C19 poor metabolizer patients with advanced/recurrent non-small-cell lung cancer. The pharmacokinetic profile and antitumor activity of ARQ 197 administered alone or in combination with erlotinib will also be determined as secondary endpoints.

Official Title
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A Phase I Study of ARQ 197 in Combination With Erlotinib in CYP2C19 Poor Metabolizer Patients With Advanced/Recurrent Non-Small-Cell Lung Cancer

Conditions
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Advanced/Recurrent Non-small-cell Lung Cancer

Intervention / Treatment
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* Drug: ARQ 197 and Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary written informed consent for study participation must be obtained A histologically or cytologically confirmed advanced/recurrent non-small-cell lung cancer History of ≥1 prior chemotherapy regimen (treatment with EGFR tyrosine kinase inhibitors will be counted as one regimen) ECOG PS of 0 or 1 Life expectancy of ≥3 months Poor metabolizers as defined by CYP2C19 genotype Exclusion Criteria: Anti-cancer chemotherapy, anti-cancer therapy with EGFR-TKI, hormone therapy, radiotherapy, immunotherapy, other investigational agents or anti-cancer antibody therapy within 28 days prior to ARQ 197 dose Surgery for cancer within 28 days prior to ARQ 197 dose Active double cancer Known symptomatic brain metastases An intercurrent illness that is uncontrolled (e.g., infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic arrhythmia, interstitial pneumonia) Pregnant or lactating Subjects who wish to have a child and who would not agree to use contraceptive measures

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARQ 197 and Erlotinib<br>ARQ 197 and erlotinib hydrochloride | Drug: ARQ 197 and Erlotinib<br>* Orally twice daily administration of ARQ197 and orally once daily administration of erlotinib hydrochloride<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-Limiting Toxicity in the combination of tivantinib and erlotinib | Tivantinib was treated once as a single agent on Day 1. After 2 days of interruption, dayly treatments of the combination started. | DLT observation period started from the day of first single agent treatment to the day after the continuous combination treatment for 29 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of ARQ 197 | Summary statistics of plasma concentration and pharmacokinetic parameters | Plasma sample correction at pre-dose, 1, 2, 4, 6, 10, 12 and 24 hours on Day 1, and in addition, at pre-dose, 1, 2, 4, 6, 10, 12 hours on the day of the first comnibation treatment | 
| Pharmacokinetic profile of Erlotinib | Summary statistics of plasma concentration and pharmacokinetic parameters | At pre-dose, 1, 2, 4, 6, 10, 12 hours on the day of the first comnibation treatment | 
| Antitumor activity | Response rate | Baseline, and then every 6 week of imaging until discontinuation criteria met |