A Phase 3, Randomized, Double-Blinded, Placebo-Controlled Study of ARQ 197 Plus Erlotinib Versus Placebo Plus Erlotinib (ATTENTION)

A Phase 3, Randomized, Double-Blinded, Placebo-Controlled Study of ARQ 197 Plus Erlotinib Versus Placebo Plus Erlotinib in Previously Treated Subjects With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer With Wild-type Epidermal Growth Factor Receptor

The primary objective of this study is to determine if the combination regimen of ARQ 197 with erlotinib will improve overall survival (OS) compared to erlotinib monotherapy in subjects with locally advanced or metastatic non-squamous NSCLC with wild-type EGFR who have received 1 or 2 prior systemic anti-cancer therapies in the Intent-to-Treat (ITT) population.

Study Overview

• Status: Terminated
• Conditions: Non-small-cell Lung Cancer
• Intervention / Treatment: Drug: ARQ 197 and Erlotinib; Drug: Placebo and Erlotinib

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Osaka, 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

1. Male or female at least 20 years of age with life expectancy ≥ 3 months
2. Histologically or cytologically confirmed surgically unresectable locally advanced or metastatic (stage IIIB/IV) non-squamous NSCLC with wild-type (excluding major activating mutation (exon 19 deletion and/or exon 21 L858R mutation)) EGFR gene status confirmed by a highly sensitive PCR assay
3. Evaluable disease according to RECIST, Version 1.1
4. Received one or two prior lines of systemic anti-cancer therapy for advanced or metastatic disease, one of which must be a platinum-based therapy
5. ECOG performance status of 0 or 1

6. Demonstrate adequate bone marrow, liver, and renal functions, defined as:

   • ALT and AST ≤ 2.5 × upper limit of normal (ULN), total bilirubin ≤ 1.5 × ULN, ANC ≥1.5 × 10^9/L, platelet count ≥100 × 10^9/L, hemoglobin ≥9.0 g/dL, and serum creatinine ≤1.5 mg/dL.

7. Voluntary written informed consent form before performance of any study-specific procedures or tests

Exclusion Criteria

1. Prior therapy with an EGFR inhibitor and/or tivantinib
2. Any systemic anti-tumor treatment for NSCLC or investigational agents within 4 weeks prior to randomization
3. Palliative radiotherapy within 2 weeks, or radiotherapy for curative intent of target lesions within 8 weeks for chest and within 4 weeks for other areas prior to randomization
4. Major surgical procedure within 4 weeks prior to randomization
5. History of cardiac disease
6. Known symptomatic brain metastases
7. Need to breastfeed a child during or within 12 weeks of completing the study
8. Significant gastrointestinal disorder that could interfere with absorption of tivantinib and/or erlotinib
9. History of malignancy other than NSCLC
10. Known infection with HIV, active HBV or HCV
11. Clinically significant interstitial lung diseases detected by CT scan or prior history of such diseases
12. Psychiatric disease that could affect the informed consent process
13. Subjects who wish to have a child and who would not agree to use one or more contraceptive measures that are highly effective
14. Positive serum or urine pregnancy test in female subjects of childbearing potential
15. Any other significant co-morbid condition that, in opinion of the investigator/sub-investigator, would impair study participation or cooperation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARQ 197; ARQ 197 and Erlotinib	Drug: ARQ 197 and Erlotinib; Oral twice daily administration of ARQ197 and oral once daily administration of erlotinib
Placebo Comparator: Placebo; Placebo and Erlotinib	Drug: Placebo and Erlotinib; Oral twice daily administration of placebo and oral once daily administration of erlotinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall survival

Secondary Outcome Measures

Outcome Measure	Measure Description
Progression free survival
Number of patients with adverse events
Objective response rate	Each assessment will be determined based on RECIST criteria version 1.1 by investigator

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Publications and helpful links

General Publications

• Yoshioka H, Azuma K, Yamamoto N, Takahashi T, Nishio M, Katakami N, Ahn MJ, Hirashima T, Maemondo M, Kim SW, Kurosaki M, Akinaga S, Park K, Tsai CM, Tamura T, Mitsudomi T, Nakagawa K. A randomized, double-blind, placebo-controlled, phase III trial of erlotinib with or without a c-Met inhibitor tivantinib (ARQ 197) in Asian patients with previously treated stage IIIB/IV nonsquamous nonsmall-cell lung cancer harboring wild-type epidermal growth factor receptor (ATTENTION study). Ann Oncol. 2015 Oct;26(10):2066-72. doi: 10.1093/annonc/mdv288. Epub 2015 Jul 7.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: June 17, 2011
• First Submitted That Met QC Criteria: June 17, 2011
• First Posted (Estimate): June 21, 2011

Study Record Updates

• Last Update Posted (Estimate): December 7, 2016
• Last Update Submitted That Met QC Criteria: December 5, 2016
• Last Verified: December 1, 2016

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: ARQ197-006