Trial record 1 of 1 for:    NCT01244191
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Tivantinib Plus Erlotinib Versus Placebo Plus Erlotinib for the Treatment of Non-squamous, Non-small-cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01244191
Recruitment Status : Completed
First Posted : November 19, 2010
Last Update Posted : May 9, 2017
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

November 17, 2010
November 19, 2010
May 9, 2017
November 2010
August 2013   (Final data collection date for primary outcome measure)
Overall survival of participants [ Time Frame: Date of randomization to ≤ 30 months ]
The overall survival (OS) will be the primary efficacy endpoint for this study. OS is defined as the time from the date of randomization to the date of death from any cause. If there is no death reported for a subject before the cut-off date for OS analysis, OS will be censored at the last contact date at which the subject is known to be alive.
Same as current
Complete list of historical versions of study NCT01244191 on Archive Site
  • Progression-free survival (PFS) in the Intent-To-Treat population [ Time Frame: Date of randomization to ≤ 30 months ]
    Progression-Free Survival (PFS) is defined as the time from the date of randomization to the date of the first objective documentation of disease progression per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, criteria, or date of death from any cause (whichever comes first).
  • Overall survival(OS) in subjects with epidermal growth factor receptor (EGFR) wild type (WT) non-small-cell lung cancer [ Time Frame: Date of randomization to ≤ 30 months ]
    This secondary efficacy endpoint relates to the OS in the EGFR WT subpopulation
Same as current
Not Provided
Not Provided
Tivantinib Plus Erlotinib Versus Placebo Plus Erlotinib for the Treatment of Non-squamous, Non-small-cell Lung Cancer
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of ARQ197 Plus Erlotinib Versus Placebo Plus Erlotinib in Previously Treated Subjects With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer (NSCLC)
This study is to determine if the combination regimen of tivantinib with erlotinib will improve overall survival relative to erlotinib alone in subjects with locally advanced or metastatic non-squamous, non-small cell lung cancer who have received 1 or 2 prior systemic anti-cancer therapies.
Not Provided
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Non Squamous, Non-small-cell Lung Cancer
  • Drug: Tivantinib
    Tivantinib 720 mg daily as 3 x 120 mg oral tablets given twice a day
    Other Name: ARQ197
  • Drug: Placebo
    Tivantinib Placebo tablets given twice a day
    Other Name: No drug
  • Drug: Erlotinib
    Erlotinib 150 mg oral tablets, given once a day
  • Experimental: Tivantinib and erlotinib
    Tivantinib 720 mg daily (360 mg twice a day) in combination with 150 mg of erlotinib, given once a day
    • Drug: Tivantinib
    • Drug: Erlotinib
  • Active Comparator: Placebo and erlotinib
    Tivantinib placebo given twice a day in combination with 150 mg of erlotinib, given once a day
    • Drug: Placebo
    • Drug: Erlotinib

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
November 2016
August 2013   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically or cytologically confirmed surgically unresectable locally advanced or metastatic (stage IIIB/IV) non-squamous non-small-cell lung cancer.
  • Measurable disease and documented disease progression following last prior therapy according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, Version 1.1.
  • Have received one or two prior lines of systemic anti-cancer therapy therapy for advanced or metastatic disease, one of which must be a platinum-doublet therapy. Patients who received only adjuvant treatment will be eligible only if disease progression occurred <6 months after completion of adjuvant therapy. Prior maintenance therapy is allowed and will be considered as the same line of therapy when continued without discontinuation after initiation of a treatment regimen.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Resolution of any toxic effects of prior therapy (including radiotherapy) according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0, Grade ≤1 (with the exception of alopecia and ≤grade 2 neuropathy). Subject must have recovered from significant surgery-related complications.
  • Demonstrate adequate bone marrow, liver, and renal functions, defined as:
  • ALT, AST, and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN) in subjects with no liver metastasis and ≤5.0 x ULN in subjects with liver metastasis.
  • Total bilirubin ≤ 1.5 × ULN (≤ 4 × ULN total and ≤1.5 × ULN direct bilirubin is acceptable for subjects with Gilbert's syndrome).
  • ANC ≥1.5 × 10^9/L.
  • Platelet count ≥100 × 10^9/L.
  • Hemoglobin ≥9.0 g/dL (transfusion and/or growth factor support allowed).
  • Serum creatinine ≤1.5 × ULN or creatinine clearance ≥ 60 mL/min.
  • Archival and/or fresh biopsy tissue sample must be available for biomarker determination. The status of the following biomarkers will be collected in this study: EGFR and KRAS mutation status prior to randomization, and MET status post randomization
  • If of child-bearing/reproductive potential (female or male), must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received
  • If female and of childbearing potential, must have a negative result of a pregnancy test (serum or urine) within 72 hours prior to initiating study treatment.
  • Must have signed and dated an approved Informed Consent Form (Including HIPAA authorization, if applicable) before performance of any study-specific procedures or tests. Subjects must be fully informed about their illness and the investigational nature of the study protocol (including forseeable risks and possible side effects)

Exclusion Criteria:

  • Prior therapy with an EGFR inhibitor and/or ARQ 197 (or other known c-MET inhibitor).
  • Receipt of any systemic anti-tumor treatment for NSCLC within 3 weeks prior to randomization.
  • Receipt of palliative radiotherapy within 2 weeks or radiotherapy for curative intent of target lesions within 3 weeks prior to randomization. Lesions subjected to radiotherapy within 3 weeks prior to randomization may not be used as target lesions.
  • Major surgical procedure within 3 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 symptomatic bradycardia (subjects with asymptomatic bradycardia and heart rate above 50 bpm are allowed) or other cardiac arrhythmia defined as ≥Grade 2 according to NCI 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 (CNS) metastasis (to be enrolled in the study, subjects must have confirmation of stable disease by MRI or computed tomography (CT) scan within 4 weeks of randomization and have CNS metastases well controlled by steroids, anti-epileptics or other symptom-relieving medications).
  • Need to breastfeed a child during or within 12 weeks of completing the study.
  • Significant gastrointestinal disorder that, in the opinion of the investigator, could interfere with absorption of ARQ 197 and/or erlotinib (eg, Crohn's disease, small or large bowel resection, malabsorption syndrome).
  • Inability or unwillingness to swallow the complete doses of ARQ 197 or erlotinib.
  • Any known contraindication to treatment with, including hypersensitivity to, ARQ 197 or erlotinib.
  • History of malignancy other than NSCLC within the 5 years prior to randomization, with the exceptions of adequately treated intraepithelial carcinoma of the cervix uteri; prostate carcinoma with a prostate-specific antigen value <0.2 ng/mL; or basal or squamous-cell carcinoma of the skin.
  • Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).
  • Any other significant co-morbid condition that, in opinion of the investigator, would impair study participation or cooperation.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Chile,   Czechia,   Denmark,   France,   Germany,   Hungary,   Italy,   Mexico,   Netherlands,   Peru,   Poland,   Romania,   Russian Federation,   Spain,   Sweden,   United Kingdom,   United States
Czech Republic
2010-022365-10 ( EudraCT Number )
Not Provided
Not Provided
Daiichi Sankyo, Inc.
Daiichi Sankyo, Inc.
Not Provided
Daiichi Sankyo, Inc.
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP