Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
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ClinicalTrials.gov Identifier: NCT01395758 |
Recruitment Status :
Completed
First Posted : July 18, 2011
Results First Posted : April 3, 2018
Last Update Posted : April 3, 2018
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Metastatic Non-Small Cell Lung Cancer | Drug: ARQ 197 plus erlotinib Drug: Pemetrexed, docetaxel or gemcitabine | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 96 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Study Start Date : | July 2011 |
Actual Primary Completion Date : | August 2016 |
Actual Study Completion Date : | August 2016 |

Arm | Intervention/treatment |
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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 Name: 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.
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Drug: Pemetrexed, docetaxel or gemcitabine
Investigator's choice of a single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered according to the approved label. |
- 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.
- 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.
- 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.
- 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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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)
- Subjects must agree to allow testing for c-Met status if archival and/or fresh tissue biopsy samples are available.
Exclusion Criteria:
- 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01395758
United States, California | |
Stanford, California, United States, 94305 | |
United States, District of Columbia | |
Washington, District of Columbia, United States, 20057 | |
United States, Florida | |
Weston, Florida, United States, 33331 | |
United States, Georgia | |
Atlanta, Georgia, United States, 30341 | |
United States, Illinois | |
Chicago, Illinois, United States, 60611 | |
United States, Kansas | |
Kansas City, Kansas, United States, 66160 | |
United States, Maryland | |
Baltimore, Maryland, United States, 21205 | |
United States, Massachusetts | |
Boston, Massachusetts, United States, 02114 | |
Burlington, Massachusetts, United States, 01805 | |
United States, New York | |
New York, New York, United States, 10016 | |
United States, Pennsylvania | |
Pittsburgh, Pennsylvania, United States, 15232 | |
United States, South Carolina | |
Charleston, South Carolina, United States, 29425 | |
United States, Texas | |
Dallas, Texas, United States, 75390 |
Responsible Party: | ArQule |
ClinicalTrials.gov Identifier: | NCT01395758 |
Other Study ID Numbers: |
ARQ 197-218 |
First Posted: | July 18, 2011 Key Record Dates |
Results First Posted: | April 3, 2018 |
Last Update Posted: | April 3, 2018 |
Last Verified: | March 2018 |
KRAS mutation metastatic NSCLC |
Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Gemcitabine Docetaxel Erlotinib Hydrochloride Pemetrexed Antimetabolites, Antineoplastic |
Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Tubulin Modulators Antimitotic Agents Mitosis Modulators Protein Kinase Inhibitors Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors |