A Study of ARQ 197 in Combination With Erlotinib

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced/Recurrent Non-small-cell Lung Cancer
• Intervention / Treatment: Drug: ARQ 197 and Erlotinib

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Shizuoka, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARQ 197 and Erlotinib; ARQ 197 and erlotinib hydrochloride	Drug: ARQ 197 and Erlotinib; Orally twice daily administration of ARQ197 and orally once daily administration of erlotinib hydrochloride

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2010
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: November 29, 2010
• First Submitted That Met QC Criteria: December 1, 2010
• First Posted (Estimate): December 2, 2010

Study Record Updates

• Last Update Posted (Actual): March 15, 2017
• Last Update Submitted That Met QC Criteria: March 14, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: ARQ 197-005