ARQ 197 Plus Erlotinib Versus Placebo Plus Erlotinib for the Treatment of Non-squamous, Non-small-cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Daiichi Sankyo Development Limited
ArQule
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT01244191
First received: November 17, 2010
Last updated: September 30, 2013
Last verified: September 2013
  Purpose

This study is to determine if the combination regimen of ARQ 197 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.


Condition Intervention Phase
Non Squamous, Non-small-cell Lung Cancer
Drug: Tivantinib (ARQ 197) plus erlotinib
Drug: ARQ 197 placebo plus erlotinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, 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 (NSCLC)

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • Overall survival of participants [ Time Frame: Date of randomization to ≤ 30 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Progression-free survival (PFS) in the Intent-To-Treat population [ Time Frame: Date of randomization to ≤ 30 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    This secondary efficacy endpoint relates to the OS in the EGFR WT subpopulation


Estimated Enrollment: 988
Study Start Date: November 2010
Estimated Study Completion Date: July 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARQ 197 plus erlotinib
720 mg daily (360 mg twice a day) of ARQ197 in combination with 150 mg of erlotinib, given once a day
Drug: Tivantinib (ARQ 197) plus erlotinib
ARQ 197 720 mg daily (360 mg oral tablets given twice a day) in combination with erlotinib 150 mg oral tablets, given once a day
Other Name: Tivantinib
Active Comparator: Placebo for ARQ 197 plus erlotinib
ARQ 197 placebo given twice a day in combination with 150 mg of erlotinib, given once a day
Drug: ARQ 197 placebo plus erlotinib
ARQ 197 oral placebo tablets given twice a day in combination with erlotinib 150 mg oral tablets, given once a day

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01244191

  Hide Study Locations
Locations
United States, Arizona
Tucson, Arizona, United States, 85715
Tucson, Arizona, United States, 85704
Tucson, Arizona, United States, 85710
Tucson, Arizona, United States, 85724-5024
United States, California
Los Angeles, California, United States, 90048
Oxnard, California, United States
Rancho Mirage, California, United States, 92270
Rancho Mirage, California, United States, 39800
Santa Monica, California, United States, 90404
United States, Colorado
Aurora, Colorado, United States, 80012
Boulder, Colorado, United States, 80303
Colorado Springs, Colorado, United States, 80909
Colorado Springs, Colorado, United States, 80907
Denver, Colorado, United States, 80218
Denver, Colorado, United States, 80220
Lakewood, Colorado, United States, 80228
Littleton, Colorado, United States, 80120
Lone Tree, Colorado, United States, 80124
Longmont, Colorado, United States, 80501
Parker, Colorado, United States, 80138
Thornton, Colorado, United States, 80260
United States, Delaware
Newark, Delaware, United States, 19713
United States, Florida
Fort Myers, Florida, United States, 33916
Miami Beach, Florida, United States, 33012
Pensacola, Florida, United States, 32504
United States, Georgia
Atlanta, Georgia, United States, 30341
Austell, Georgia, United States, 30106
Carrollton, Georgia, United States, 30117
Cartersville, Georgia, United States, 30121
Douglasville, Georgia, United States, 30134
Marietta, Georgia, United States, 30060
United States, Illinois
Chicago, Illinois, United States, 60637
United States, Indiana
Carmel, Indiana, United States, 46032
Fishers, Indiana, United States, 46037
Goshen, Indiana, United States, 46526
Greenfield, Indiana, United States, 46140
Indianapolis, Indiana, United States, 46219
Indianapolis, Indiana, United States, 46227
Indianapolis, Indiana, United States, 48202
United States, Kentucky
Lexington, Kentucky, United States
Louisville, Kentucky, United States
United States, Maryland
Towson, Maryland, United States, 21204
United States, Massachusetts
Boston, Massachusetts, United States, 02114
United States, Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
St. Louis, Missouri, United States, 63110
United States, Nebraska
Grand Island,, Nebraska, United States, 68803
Omaha, Nebraska, United States, 68198
United States, Nevada
Henderson, Nevada, United States, 89052
Henderson, Nevada, United States, 89074
Las Vegas, Nevada, United States, 89169
Las Vegas, Nevada, United States, 89148
Las Vegas, Nevada, United States, 89128
United States, New Jersey
East Orange, New Jersey, United States, 07018
United States, New Mexico
Albuquerque, New Mexico, United States, 87131
United States, New York
Bronx, New York, United States, 10467
Buffalo, New York, United States, 14263
Goshen, New York, United States, 10924
Latham, New York, United States
New York, New York, United States, 10032
United States, Ohio
Cincinnati, Ohio, United States, 45242
Clevland, Ohio, United States, 44195
Kettering, Ohio, United States
United States, Oregon
Eugene, Oregon, United States, 97401
Portland, Oregon, United States, 97239
Portland, Oregon, United States, 97225
Portland, Oregon, United States, 97227
Portland, Oregon, United States, 97213
Springfield, Oregon, United States, 97477
Tualatin, Oregon, United States, 97062
United States, Pennsylvania
Harrisburg, Pennsylvania, United States, 17109
Hershey, Pennsylvania, United States, 17033-0850
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Columbia, South Carolina, United States, 29120
Easley, South Carolina, United States, 29640
Greenville, South Carolina, United States, 29605
Greenville, South Carolina, United States, 29615
Greenville, South Carolina, United States, 29601
Spartanburg, South Carolina, United States, 29307
United States, Tennessee
Barlett, Tennessee, United States, 38138
Chattanooga, Tennessee, United States, 37404
Germantown, Tennessee, United States, 38138
Knoxville, Tennessee, United States, 37909
Memphis, Tennessee, United States, 38104
Nashville, Tennessee, United States, 37203
Southaven, Tennessee, United States, 38671
United States, Texas
Austin, Texas, United States, 78731
Austin, Texas, United States, 78745
Austin, Texas, United States, 78705
Austin, Texas, United States, 78758
Cedar Park, Texas, United States, 78731
Dallas, Texas, United States, 75246
Dallas, Texas, United States, 75216-9982
Fort Worth, Texas, United States, 76132
Forth Worth, Texas, United States, 76104
Kyle, Texas, United States, 78640
Round Rock, Texas, United States, 78681
Round Rock, Texas, United States, 78665
San Marcos, Texas, United States, 78666
United States, Utah
Salt Lake City, Utah, United States, 84112
United States, Virginia
Arlington, Virginia, United States, 22205
Fairfax, Virginia, United States, 22031
Gainesville, Virginia, United States, 20155
Leesburg, Virginia, United States, 20176
Midlothian, Virginia, United States, 23112
Richmond,, Virginia, United States, 23298
Winchester, Virginia, United States, 22601
Woodbridge, Virginia, United States, 22191
United States, Washington
Seattle, Washington, United States, 98104
Vancouver, Washington, United States, 98684
Vancouver, Washington, United States, 98686
Yakima, Washington, United States, 98902
Argentina
Rosario, Santa Fe, Argentina, S2000SDV
Buenos Aires, Argentina
Cordoba, Argentina, X5000AA1
Rio Negro, Argentina
San Miguel de Tucuman, Argentina
Tucuman, Argentina
Australia, Queensland
Greenslopes, Queensland, Australia, 4120
Australia
Camperdown, Australia
Kogarah, Australia
Perth, Australia
St. Leonards, Australia, 2065
Wollongong, Australia
Woodville, Australia
Austria
Salzburg, Austria, 5020
Wels, Austria, A-4600
Belgium
Brasschaat, Belgium, 2930
Brussels, Belgium
Duffel, Belgium, 2570
Brazil
Salvador, BA, Brazil, 41253-190
Rio de Janeiro, RJ, Brazil, 20231-050
Passo Fundo, RS, Brazil, 99010-080
Passo Fundo, RS, Brazil, 99010-260
Porto Alegre, RS, Brazil, 90430-090
Joinville, Santa Catarina, Brazil, 89202
Joinville, SC, Brazil, 89202050
Ijui, Brazil
Porto Alegre, Brazil
Sao Paulo, Brazil
Sao Paulo, Brazil, 01224-10
Canada, Alberta
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Victoria, British Columbia, Canada, V8R lC3
Canada, Manitoba
Winnipeg, Manitoba, Canada, RSE 0V9
Canada, Ontario
Thunder Bay, Ontario, Canada, P7B6V4
Toronto, Ontario, Canada, M5G 1X5
Canada, Quebec
Montreal, Quebec, Canada, H1T 2M4
Canada
London Ontario, Canada, N6A 4L6
Montreal, Canada, H2W 1S6
Quebec, Canada, G1V 4G5
Surrey, BC, Canada, V3V 1Z2
Toronto, Canada, M5G 2M9
Chile
Santiago, Chile, 8380455
Santiago, Chile, 7500921
Santiago, Chile, 7520378
Santiago, Chile, 7500710
Czech Republic
Ostrava, Czech Republic, 70384
Pardubice, Czech Republic, 53203
Praha, Czech Republic, 12808
Usti nad Labem, Czech Republic
Denmark
Herlev, Denmark, DK-2730
Naestved, Denmark, 4700
Odense, Denmark, DK-5000
France
Besancon, France, 25000
Brest, France, 29609
Caen Cedex, France, 14033
Grenoble, France, 9
Lille, France, 59037
Marseille Cedex, France
Paris, France, 75013
Paris Cedex, France, 75230
Pierre Benite, France, 69495
Rennes Cedex, France, 35033
Saint-Priest en Jarez, France
Strasbourg Cedex, France
Toulouse Cedex, France, 31059
Tours Cedex, France, 37044
Villejuif, France, 94805
Germany
Bad Berka, Germany, 99437
Berlin, Germany, 12203
Berrlin, Germany, 10117
Erfurt, Germany
Essen, Germany, 45122
Esslingen, Germany, 73730
Gauting, Germany, 82131
Grobhansdorf, Germany, 22927
Halle, Germany, 06120
Hamburg, Germany, 21075
Hannover, Germany, 30625
Karlsruhe, Germany, 76137
Kassel, Germany, 34125
Koln, Germany, 51109
Leverkusen, Germany, 51375
Lowenstein, Germany, 74245
Mainz, Germany, 55131
Mannheim, Germany, 68167
Munchen, Germany, 80336
Munchen, Germany, 81925
Munchen, Germany
Porta Westfalica, Germany, 32457
Rheine, Germany, 48431
Villingen-Schwenningen, Germany, 78050
Hungary
Deszk, Hungary, H-6772
Gyula, Hungary, H-5703
Matrahaza, Hungary, H-3233
Szekesfehervar, Hungary, H-8000
Szolnok, Hungary, H-5000
Italy
Ancona, Italy
Avellino, Italy, 83100
Aviano, Italy, 33081
Bari, Italy, 70124
Catania, Italy, 95126
Cremona, Italy, 26100
Cuneo, Italy, 12100
Firenze, Italy, 50134
Livorno, Italy, 57100
Milano, Italy, 20162
Modena, Italy, 41124
Monza, Italy, 20900
Napoli, Italy, 80131
Novara, Italy, 28100
Orbassano, Italy, 10043
Padova, Italy, 35128
Palermo, Italy, 90146
Parma, Italy, 43126
Perugia, Italy, 06132
Roma, Italy, 00152
Rozzano, Italy, 20089
Sassari, Italy, 07100
Sondalo, Italy, 23035
Sora, Italy, 03039
Torino, Italy
Mexico
Mexico, DF, Mexico
Guadalajara, Mexico, 44280
Mexico City, Mexico
Monterrey, Nuevo Leon, Mexico, 64460
Oaxaca, Mexico, 68000
Oaxaca, Mexico, 70000
Netherlands
Enschede, ER, Netherlands, 7513
Helmond, HA, Netherlands, 5707
Amsterdam, Netherlands
Peru
Arequipa, Peru
Lima, Peru
Lima, Peru, 27
Lima, Peru, 41
Lima, Peru, 34
Poland
Bystra, Poland, 43-360
Krakow, Poland, 31302
Lublin, Poland
Olsztyn, Poland, 31302
Opole, Poland
Poznan, Poland, 60-569
Poznan, Poland
Prabuty, Poland, 82550
Rzeszow, Poland, 35922
Szczecin, Poland, 70891
Torun, Poland
Walbrzych, Poland
Romania
Cluj-Napoca, Romania, 400015
Craiova, Romania, 200385
Oradea, Romania, 410167
Russian Federation
Chelyabinsk, Russian Federation, 454087
Irkutsk, Russian Federation, 664035
Izhevsk, Russian Federation, 426009
Kursk, Russian Federation, 305035
Moscow, Russian Federation, 115478
Moscow, Russian Federation, 125367
Novgorod, Russian Federation, 603081
Novosibirsk, Russian Federation
Pyatigorsk, Russian Federation, 357502
St Petersburg, Russian Federation, 197758
St Petersburg, Russian Federation, 198255
St. Petersburg, Russian Federation, 197022
Tula, Russian Federation, 300040
Tuymen, Russian Federation, 625041
Spain
Alicante, Spain, 03010
Barakaldo (Bilbao), Spain, 48903
Barcelona, Spain, 08003
Barcelona, Spain, 08907
Coruna, Spain, 15006
Coruna, Spain, 15009
La Laguna, Spain, 38320
Madrid, Spain
Madrid, Spain, 28034
Madrid, Spain, 28041
Malaga, Spain, 29010
Manresa, Spain, 08243
Oviedo, Spain, 33006
Palma de Mallorca, Spain, 07010
Sabadell, Spain, 08208
Santiago de Compostela, Spain, 15706
Sevilla, Spain, 41013
Sevilla, Spain, 41700
Valencia, Spain, 46010
Vigo-Pontevedra, Spain, 36204
Zaragoza, Spain, 50009
Sweden
Linkoping, Sweden, 581 85
Lund, Sweden
United Kingdom
Guildford, Surrey, United Kingdom, GU2 7XX
Aberdeen, United Kingdom, AB25 2ZN
Glasgow, United Kingdom, G12OYN
Londin, United Kingdom, NW1 2PG
London, United Kingdom, W6 9RF
Manchester, United Kingdom, M20 4BX
Nottingham, United Kingdom, NG5 1PB
Sheffield, United Kingdom, S10 2SJ
Sponsors and Collaborators
Daiichi Sankyo Inc.
Daiichi Sankyo Development Limited
ArQule
  More Information

No publications provided by Daiichi Sankyo Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT01244191     History of Changes
Other Study ID Numbers: ARQ 197-A-U302, 2010-022365-10
Study First Received: November 17, 2010
Last Updated: September 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Daiichi Sankyo Inc.:
Non squamous, non-small-cell lung cancer
Epidermal growth factor receptor, wild type
c-Met inhibitor

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014