Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

NCT01395758 | Completed Phase 2 Results

• 1 other identifier: ARQ 197-218
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 13

Brief Summary

The purpose of this study is to evaluate progression-free survival among subjects with KRAS mutation positive Non-Small Cell Lung Cancer (NSCLC) treated with erlotinib plus tivantinib (ARQ 197) compared to single agent chemotherapy.

Conditions

Metastatic Non-Small Cell Lung Cancer

Keywords

KRAS mutation; metastatic NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) Among Subjects With KRAS Mutation Positive NSCLC (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Single Agent Chemotherapy.

  Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) criteria as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or progression of existing non-target lesions are also considered progression.

  Date of randomization until disease progression per RECIST (v 1.1) or death from any cause, whichever came first, assessed up to 24 months.

Secondary Outcomes (3)

• Overall Survival (OS) Among All Eligible Subjects (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Chemotherapy.

  Date of randomization to the date of death from any cause, assessed up to 24 months

• Objective Response Rate (ORR) Among All Eligible Subjects (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Chemotherapy.

  Date of randomization to the date of death from any cause or to the date that the subject discontinues from the study, assessed up to 24 months

• ORR Among Subjects in the Crossover Period Treated With Erlotinib Plus Tivantinib

  Date of randomization to the date of death from any cause or to the date that the subject discontinues from the study, assessed up to 24 months.

Study Arms (2)

tivantinib (ARQ 197) plus erlotinib arm

EXPERIMENTAL

Eligible subjects will be randomly assigned to receive erlotinib plus tivantinib (ARQ 197). Treatment will be open-label and continue until progression of disease, unacceptable toxicity, or another discontinuation criterion is met.

Drug: ARQ 197 plus erlotinib

Chemotherapy arm

ACTIVE COMPARATOR

Investigator's choice of single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered in 3-week cycles according to the approved label until disease progression or unacceptable toxicity. Subjects who discontinued chemotherapy can be switched to the crossover arm (tivantinib plus erlotinib) and continue treatment until disease progression or unacceptable toxicity.

Drug: Pemetrexed, docetaxel or gemcitabine

Interventions

ARQ 197 plus erlotinib DRUG

Eligible subjects will be randomly assigned to receive erlotinib plus ARQ 197.

Also known as: Tivantinib

tivantinib (ARQ 197) plus erlotinib arm

Pemetrexed, docetaxel or gemcitabine DRUG

Investigator's choice of a single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered according to the approved label.

Chemotherapy arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide signed and dated informed consent prior to study-specific screening procedures
• Male or female at least 18 years of age
• Histologically or cytologically confirmed inoperable locally advanced or metastatic (stage IVA/IVB) NSCLC
• Documented KRAS mutation positive status (per Lung Cancer Mutation Consortium \[LCMC\] guidelines; see www.golcmc.com)
• At least one prior chemotherapy regimen for advanced NSCLC
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, Version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
• Male or female subjects 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
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 × ULN with metastatic liver disease
• Total bilirubin ≤ 1.5 × ULN
• Serum creatinine ≤ 1.5 × ULN
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L
• Hemoglobin ≥ 10 g/dL (transfusion is allowed at least 7 days prior to randomization)

You may not qualify if:

• Previous receipt of erlotinib or other epidermal growth factor receptor (EGFR) inhibitors
• Previous receipt of any c-MET inhibitor (a receptor tyrosine kinase) or other c-MET-targeted therapy, including ARQ 197, MetMab, crizotinib
• Prior receipt of chemotherapy agent selected for administration in this study (e.g., if subject was treated with gemcitabine, he is not eligible to receive gemcitabine in this study but eligible to receive pemetrexed or docetaxel).
• Inability or unwillingness to receive ARQ 197, erlotinib, docetaxel, gemcitabine, and/or pemetrexed including contraindications, hypersensitivity, or prior administration
• Receipt of any anti-tumor treatment for NSCLC within 3 weeks (2 weeks for radiotherapy) prior to randomization
• Pregnant or breastfeeding
• Significant gastrointestinal disorder that could, in the opinion of the Investigator, interfere with the absorption of ARQ 197 and/or erlotinib
• Any other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation
• Other malignancies within the last three years, with the exception of adequately treated intraepithelial carcinoma of the cervix uteri, prostate carcinoma with a prostate-specific antigen (PSA) value \< 0.2 ng/mL or basal or squamous cell carcinoma of the skin
• Known human immunodeficiency virus (HIV), or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Major surgical procedure within 4 weeks prior to randomization
• History of cardiac disease: Congestive heart failure defined as Class II to IV per New York Heart Association classification; Active coronary artery disease; Previously diagnosed bradycardia or other cardiac arrhythmia defined as ≥ Grade 2 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled hypertension; Myocardial infarction that occurred within 6 months prior to study entry (myocardial infarction that occurred \> 6 months prior to study entry is permitted)
• Clinically unstable central nervous system metastasis (to be enrolled in the study, subjects must have confirmation of stable disease by MRI or CT scan within 4 weeks of randomization and have central nervous system \[CNS\] metastases well controlled by steroids, anti-epileptics or other symptom-relieving medications)
• Known EGFR-mutation positive status

Sponsors & Collaborators

• ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA): lead

Study Sites (13)

Unknown Facility

Stanford, California, 94305, United States

Location

Unknown Facility

Washington D.C., District of Columbia, 20057, United States

Location

Unknown Facility

Weston, Florida, 33331, United States

Location

Unknown Facility

Atlanta, Georgia, 30341, United States

Location

Unknown Facility

Chicago, Illinois, 60611, United States

Location

Unknown Facility

Kansas City, Kansas, 66160, United States

Location

Unknown Facility

Baltimore, Maryland, 21205, United States

Location

Unknown Facility

Boston, Massachusetts, 02114, United States

Location

Unknown Facility

Burlington, Massachusetts, 01805, United States

Location

Unknown Facility

New York, New York, 10016, United States

Location

Unknown Facility

Pittsburgh, Pennsylvania, 15232, United States

Location

Unknown Facility

Charleston, South Carolina, 29425, United States

Location

Unknown Facility

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

ARQ 197; Erlotinib Hydrochloride; Pemetrexed; Docetaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Brian Schwartz, MD Chief Medical Officer
• Organization: ArQule, Inc.

ClinicalTrials@arqule.com

781-994-0300

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2011
• First Posted: July 18, 2011
• Study Start: July 1, 2011
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: April 3, 2018
• Results First Posted: April 3, 2018

Record last verified: 2018-03

Locations

US (13)