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

March 5, 2018 updated by: ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

A Phase 2 Randomized Open-label Study of Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Previously Treated KRAS Mutation Positive Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a randomized, open-label Phase 2 study designed to compare treatment with erlotinib plus tivantinib (ARQ 197) versus single agent chemotherapy in subjects with previously treated KRAS mutation positive NSCLC. Eligible subjects are randomly assigned to receive erlotinib plus tivantinib or one of three (based on Investigator's choice) single-agent chemotherapy agents including pemetrexed, docetaxel, or gemcitabine.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
96

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
    • District of Columbia
      • Washington, District of Columbia, United States, 20057
    • Florida
      • Weston, Florida, United States, 33331
    • Georgia
      • Atlanta, Georgia, United States, 30341
    • Illinois
      • Chicago, Illinois, United States, 60611
    • Kansas
      • Kansas City, Kansas, United States, 66160
    • Maryland
      • Baltimore, Maryland, United States, 21205
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
      • Burlington, Massachusetts, United States, 01805
    • New York
      • New York, New York, United States, 10016
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
    • South Carolina
      • Charleston, South Carolina, United States, 29425
    • Texas
      • Dallas, Texas, United States, 75390

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Provide signed and dated informed consent prior to study-specific screening procedures
  2. Male or female at least 18 years of age
  3. Histologically or cytologically confirmed inoperable locally advanced or metastatic (stage IVA/IVB) NSCLC
  4. Documented KRAS mutation positive status (per Lung Cancer Mutation Consortium [LCMC] guidelines; see www.golcmc.com)
  5. At least one prior chemotherapy regimen for advanced NSCLC
  6. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, Version 1.1
  7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  8. 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
  9. Females of childbearing potential must have a negative serum pregnancy test
  10. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 × ULN with metastatic liver disease
  11. Total bilirubin ≤ 1.5 × ULN
  12. Serum creatinine ≤ 1.5 × ULN
  13. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
  14. Platelets ≥ 100 x 10^9/L
  15. Hemoglobin ≥ 10 g/dL (transfusion is allowed at least 7 days prior to randomization)
  16. Subjects must agree to allow testing for c-Met status if archival and/or fresh tissue biopsy samples are available.

Exclusion Criteria:

  1. Previous receipt of erlotinib or other epidermal growth factor receptor (EGFR) inhibitors
  2. Previous receipt of any c-MET inhibitor (a receptor tyrosine kinase) or other c-MET-targeted therapy, including ARQ 197, MetMab, crizotinib
  3. 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).
  4. Inability or unwillingness to receive ARQ 197, erlotinib, docetaxel, gemcitabine, and/or pemetrexed including contraindications, hypersensitivity, or prior administration
  5. Receipt of any anti-tumor treatment for NSCLC within 3 weeks (2 weeks for radiotherapy) prior to randomization
  6. Pregnant or breastfeeding
  7. Significant gastrointestinal disorder that could, in the opinion of the Investigator, interfere with the absorption of ARQ 197 and/or erlotinib
  8. Any other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation
  9. 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
  10. Known human immunodeficiency virus (HIV), or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  11. Major surgical procedure within 4 weeks prior to randomization
  12. 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)
  13. 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)
  14. Known EGFR-mutation positive status

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: tivantinib (ARQ 197) plus erlotinib arm

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
Eligible subjects will be randomly assigned to receive erlotinib plus ARQ 197.
Other Names:
  • Tivantinib
Active Comparator: Chemotherapy arm
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
Investigator's choice of a single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered according to the approved label.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS) Among Subjects With KRAS Mutation Positive NSCLC (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Single Agent Chemotherapy.
Time Frame: Date of randomization until disease progression per RECIST (v 1.1) or death from any cause, whichever came first, assessed up to 24 months.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS) Among All Eligible Subjects (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Chemotherapy.
Time Frame: Date of randomization to the date of death from any cause, assessed up to 24 months
OS is calculated from the date of randomization until death from any cause.
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.
Time Frame: 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
Per RECIST v1.1, Complete Response (CR) = disappearance of all lesions and Partial Response (PR) = at least 30% decrease in the sum of diameters of target lesions. ORR = (CR+PR)/# subjects.
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
Time Frame: 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.
Per RECIST v1.1, CR = disappearance of all lesions and PR = at least 30% decrease in the sum of diameters of target lesions. ORR = (CR+PR)/# subjects.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 1, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 14, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 18, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 3, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 5, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ARQ 197-218

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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