Non Squamous, Non-small-cell Lung CancerPhase 3NCT01244191
Tivantinib Plus Erlotinib Versus Placebo Plus Erlotinib for the Treatment of Non-squamous, Non-small-cell Lung Cancer
A Phase 3 study testing Tivantinib and Erlotinib in people with Non Squamous, Non-small-cell Lung Cancer, run by Daiichi Sankyo at 304 sites in 23 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Squamous, Non-small-cell Lung Cancer
- What is being tested?
- Tivantinib and Erlotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,048 participants
- Where
- 304 sitesin 23 countries
- Study dates
- 11 Jan 2011to 15 Dec 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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)
Who cannot join
- 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).
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- 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.
Trial locations and contacts
304 sites in 23 countries.
304 sites in 23 countries
United States111 sites
Study site
Albuquerque, New Mexico, 87131
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Arlington, Virginia, 22205
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Atlanta, Georgia, 30341
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Aurora, Colorado, 80012
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Austell, Georgia, 30106
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Austin, Texas, 78705
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Austin, Texas, 78731
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Austin, Texas, 78745
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Austin, Texas, 78758
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Bartlett, Tennessee, 38138
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Boston, Massachusetts, 02114
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Boulder, Colorado, 80303
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Buffalo, New York, 14263
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Carmel, Indiana, 46032
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Carrollton, Georgia, 30117
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Cartersville, Georgia, 30121
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Cedar Park, Texas, 78731
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Chattanooga, Tennessee, 37404
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Chicago, Illinois, 60637
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Cincinnati, Ohio, 45242
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Cleveland, Ohio, 44195
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Colorado Springs, Colorado, 80907
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Colorado Springs, Colorado, 80909
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Columbia, South Carolina, 29120
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Dallas, Texas, 75216-9982
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Dallas, Texas, 75246
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Denver, Colorado, 80218
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Denver, Colorado, 80220
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Douglasville, Georgia, 30134
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Easley, South Carolina, 29640
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East Orange, New Jersey, 07018
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Eugene, Oregon, 97401
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Fairfax, Virginia, 22031
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Fishers, Indiana, 46037
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Fort Myers, Florida, 33916
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Fort Worth, Texas, 76104
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Fort Worth, Texas, 76132
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Gainesville, Virginia, 20155
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Germantown, Tennessee, 38138
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Goshen, Indiana, 46526
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Goshen, New York, 10924
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Grand Island, Nebraska, 68803
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Greenfield, Indiana, 46140
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Greenville, South Carolina, 29601
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Greenville, South Carolina, 29605
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Greenville, South Carolina, 29615
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Harrisburg, Pennsylvania, 17109
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Henderson, Nevada, 89052
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Henderson, Nevada, 89074
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Hershey, Pennsylvania, 17033-0850
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Indianapolis, Indiana, 46219
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Indianapolis, Indiana, 46227
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Indianapolis, Indiana, 48202
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Kettering, Ohio
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Knoxville, Tennessee, 37909
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Kyle, Texas, 78640
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Lakewood, Colorado, 80228
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Las Vegas, Nevada, 89128
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Las Vegas, Nevada, 89148
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Las Vegas, Nevada, 89169
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Latham, New York
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Leesburg, Virginia, 20176
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Lexington, Kentucky
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Littleton, Colorado, 80120
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Lone Tree, Colorado, 80124
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Longmont, Colorado, 80501
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Los Angeles, California, 90048
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Louisville, Kentucky
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Marietta, Georgia, 30060
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Memphis, Tennessee, 38104
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Miami Beach, Florida, 33012
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Midlothian, Virginia, 23112
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Minneapolis, Minnesota, 55455
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Nashville, Tennessee, 37203
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New York, New York, 10032
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Newark, Delaware, 19713
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Omaha, Nebraska, 68198
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Oxnard, California
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Parker, Colorado, 80138
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Pensacola, Florida, 32504
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Philadelphia, Pennsylvania, 19104
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Portland, Oregon, 97213
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Portland, Oregon, 97225
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Portland, Oregon, 97227
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Portland, Oregon, 97239
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Rancho Mirage, California, 39800
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Rancho Mirage, California, 92270
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Richmond, Virginia, 23298
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Round Rock, Texas, 78665
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Round Rock, Texas, 78681
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Salt Lake City, Utah, 84112
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San Marcos, Texas, 78666
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Santa Monica, California, 90404
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Seattle, Washington, 98104
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Southaven, Tennessee, 38671
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Spartanburg, South Carolina, 29307
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Springfield, Oregon, 97477
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St Louis, Missouri, 63110
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The Bronx, New York, 10467
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Thornton, Colorado, 80260
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Towson, Maryland, 21204
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Tualatin, Oregon, 97062
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Tucson, Arizona, 85704
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Tucson, Arizona, 85710
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Tucson, Arizona, 85715
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Tucson, Arizona, 85724-5024
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Vancouver, Washington, 98684
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Vancouver, Washington, 98686
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Winchester, Virginia, 22601
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Woodbridge, Virginia, 22191
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Yakima, Washington, 98902
Italy25 sites
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Ancona
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Avellino, 83100
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Aviano, 33081
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Bari, 70124
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Catania, 95126
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Cremona, 26100
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Cuneo, 12100
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Florence, 50134
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Livorno, 57100
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Milan, 20162
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Modena, 41124
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Monza, 20900
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Naples, 80131
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Novara, 28100
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Orbassano, 10043
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Padova, 35128
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Palermo, 90146
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Parma, 43126
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Perugia, 06132
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Roma, 00152
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Rozzano, 20089
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Sassari, 07100
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Sondalo, 23035
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Sora, 03039
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Torino
Germany24 sites
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Bad Berka, 99437
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Berlin, 10117
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Berlin, 12203
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Cologne, 51109
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Erfurt
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Essen, 45122
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Esslingen am Neckar, 73730
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Gauting, 82131
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Großhansdorf, 22927
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Halle, 06120
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Hamburg, 21075
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Hanover, 30625
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Karlsruhe, 76137
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Kassel, 34125
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Leverkusen, 51375
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Löwenstein, 74245
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Mainz, 55131
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Mannheim, 68167
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München, 80336
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München, 81925
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München
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Porta Westfalica, 32457
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Rheine, 48431
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Villingen-Schwenningen, 78050
Spain21 sites
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A Coruña, 15006
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A Coruña, 15009
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Alicante, 03010
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Barakaldo, Bilbao, 48903
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Barcelona, 08003
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Barcelona, 08907
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Madrid, 28034
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Madrid, 28041
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Madrid
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Málaga, 29010
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Manresa, 08243
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Oviedo, 33006
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Palma de Mallorca, 07010
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Sabadell, 08208
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San Cristóbal de La Laguna, 38320
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Santiago de Compostela, 15706
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Seville, 41013
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Seville, 41700
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Valencia, 46010
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Vigo, Pontevedra, 36204
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Zaragoza, 50009
France15 sites
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Besançon, 25000
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Brest, 29609
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Caen, 14033
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Grenoble, 9
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Lille, 59037
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Marseille
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Paris, 75013
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Paris, 75230
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Pierre-Bénite, 69495
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Rennes, 35033
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Saint-Priest-en-Jarez
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Strasbourg
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Toulouse, 31059
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Tours, 37044
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Villejuif, 94805
Russia14 sites
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Chelyabinsk, 454087
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Irkutsk, 664035
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Izhevsk, 426009
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Kursk, 305035
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Moscow, 115478
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Moscow, 125367
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Novosibirsk
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Pyatigorsk, 357502
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Saint Petersburg, 197022
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Saint Petersburg, 197758
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Saint Petersburg, 198255
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Tula, 300040
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Tyumen, 625041
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Velikiy Novgorod, 603081
Poland12 sites
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Bystra, 43-360
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Krakow, 31302
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Lublin
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Olsztyn, 31302
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Opole
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Poznan, 60-569
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Poznan
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Prabuty, 82550
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Rzeszów, 35922
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Szczecin, 70891
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Torun
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Wałbrzych
Brazil11 sites
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Ijuí
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Joinville, Santa Catarina, 89202050
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Joinville, Santa Catarina, 89202
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Passo Fundo, Rio Grande do Sul, 99010-080
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Passo Fundo, Rio Grande do Sul, 99010-260
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Porto Alegre, Rio Grande do Sul, 90430-090
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Porto Alegre
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Rio de Janeiro, Rio de Janeiro, 20231-050
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Salvador, Estado de Bahia, 41253-190
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São Paulo, 01224-10
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São Paulo
Canada11 sites
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Edmonton, Alberta, T6G 1Z2
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London, Ontario, N6A 4L6
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Montreal, Quebec, H1T 2M4
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Montreal, H2W 1S6
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Québec, G1V 4G5
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Surrey, British Columbia, V3V 1Z2
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Thunder Bay, Ontario, P7B6V4
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Toronto, Ontario, M5G 1X5
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Toronto, M5G 2M9
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Victoria, British Columbia, V8R lC3
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Winnipeg, Manitoba, RSE 0V9
United Kingdom8 sites
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Aberdeen, AB25 2ZN
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Glasgow, G12OYN
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Guildford, Surrey, GU2 7XX
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London, NW1 2PG
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London, W6 9RF
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Manchester, M20 4BX
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Nottingham, NG5 1PB
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Sheffield, S10 2SJ
Australia7 sites
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Camperdown
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Greenslopes, Queensland, 4120
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Kogarah
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Perth
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St Leonards, 2065
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Wollongong
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Woodville
Mexico6 sites
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Guadalajara, 44280
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Mexico City, Mexico City
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Mexico City
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Monterrey, Nuevo León, 64460
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Oaxaca City, 68000
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Oaxaca City, 70000
Argentina5 sites
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Buenos Aires
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Córdoba, X5000AA1
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Rosario, Santa Fe Province, S2000SDV
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San Miguel de Tucumán
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Viedma
Hungary5 sites
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Deszk, H-6772
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Gyula, H-5703
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Mátraháza, H-3233
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Székesfehérvár, H-8000
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Szolnok, H-5000
Peru5 sites
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Arequipa
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Lima, 27
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Lima, 34
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Lima, 41
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Lima
Chile4 sites
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Santiago, 7500710
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Santiago, 7500921
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Santiago, 7520378
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Santiago, 8380455
Czechia4 sites
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Ostrava, 70384
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Pardubice, 53203
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Prague, 12808
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Ústí nad Labem
Belgium3 sites
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Brasschaat, 2930
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Brussels
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Duffel, 2570
Denmark3 sites
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Herlev, DK-2730
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Næstved, 4700
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Odense, DK-5000
Netherlands3 sites
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Amsterdam
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Enschede, ER, 7513
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Helmond, HA, 5707
Romania3 sites
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Cluj-Napoca, 400015
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Craiova, 200385
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Oradea, 410167
About this study
Official title: 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.
- Conditions
- Non Squamous, Non-small-cell Lung Cancer
- Being tested
- Tivantinib, Placebo, Erlotinib
- Keywords
- Non squamous, non-small-cell lung cancer, Epidermal growth factor receptor, c-Met inhibitor
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TivantinibDrug
Also called ARQ197
Tivantinib 720 mg daily as 3 x 120 mg oral tablets given twice a day
PlaceboDrug
Also called No drug
Tivantinib Placebo tablets given twice a day
ErlotinibDrug
Erlotinib 150 mg oral tablets, given once a day
| Study group | Role | What they receive |
|---|---|---|
| Tivantinib and erlotinib | Experimental | Tivantinib 720 mg daily (360 mg twice a day) in combination with 150 mg of erlotinib, given once a day Receives: Drug: Tivantinib; Drug: Erlotinib |
| Placebo and erlotinib | Active comparator | Tivantinib placebo given twice a day in combination with 150 mg of erlotinib, given once a day Receives: Drug: Placebo; Drug: Erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer
The overall survival (OS) was defined as the time from the date of randomization to the date of death from any cause.
Measured: Date of randomization up to date of death, up to approximately 1 year 11 months postdose
Secondary outcomes (7)
Progression-free Survival Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer
Progression-free Survival (PFS) was defined as the time from the date of randomization to the date of the first objective documentation of disease progression or date of death from any cause (whichever comes first). As per the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) criteria, progression was defined as at least a 20% increase in the sum of diameters of target lesions.
Measured: Date of randomization to disease progression or death (whichever comes first), up to 1 year 11 months postdose
Overall Survival in the Epidermal Growth Factor Receptor Gene Wild-Type Subpopulation Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Non-Squamous NSCLC
The overall survival (OS) was defined as the time from the date of randomization to the date of death from any cause.
Measured: Date of randomization up to date of death, up to approximately 1 year 11 months postdose
Progression-free Survival in the Epidermal Growth Factor Receptor (EGFR) Gene Wild-Type Subpopulation Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants Non-Squamous NSCLC
Progression-free Survival (PFS) was defined as the time from the date of randomization to the date of the first objective documentation of disease progression or date of death from any cause (whichever comes first). As per the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) criteria, progression was defined as at least a 20% increase in the sum of diameters of target lesions.
Measured: Date of randomization to disease progression or death (whichever comes first), up to 1 year 11 months postdose
Best Overall Tumor Response Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer
The best overall response was defined as the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], stable disease [SD], and progressive disease [PD]) among all overall responses recorded from the start of treatment until the participant withdrew from the study. If there was no tumor assessment after the first dose of study drug, the best overall response was classified as Inevaluable. Based on RECIST v1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.
Measured: From baseline up to disease progression or the development of unacceptable toxicity (whichever occurs first), up to 1 year 11 months postdose
Duration of Response Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer
Duration of response was defined for participants with confirmed CR or PR as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of progressive disease. Duration of SD was defined for participants whose best response was SD as the time from the randomization date to the date of the first documentation of progressive disease.
Measured: From the date of first objective response (CR or PR) or SD to date of progressive disease, up to 1 year 11 months postdose
Treatment-Emergent Adverse Events Reported in ≥5% of Participants Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Non-Squamous, Non-Small-Cell Lung Cancer
Treatment-emergent AEs (TEAEs) were defined as those AEs that occurred, having been absent before the study, or worsened in severity after the initiation of study treatment administration.
Measured: Baseline up to 30 days after last dose, up to 1 year 11 months postdose
Treatment-Emergent Adverse Events Related to Tivantinib/Placebo Experienced by ≥5% of Participants Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Non-Squamous NSCLC
Treatment-emergent AEs (TEAEs) were defined as those AEs that occurred, having been absent before the study, or worsened in severity after the initiation of study treatment administration.
Measured: Baseline up to 30 days after last dose, up to 1 year 11 months postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2010 (estimated)
- Study start11 Jan 2011
- Primary completion15 Dec 2012
- Study completion15 Dec 2012
Why it stopped: Sponsor decision due to the protocol-defined stopping boundary for futility was met based on the interim OS data.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Non Squamous, Non-small-cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 1,048 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01244191
- Sponsor's protocol ID
- ARQ197-A-U302
- Other IDs
- 2010-022365-10
- Status last verified
- Mar 2021
- First submitted
- 17 Nov 2010
- Last updated
- 6 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Scagliotti G, von Pawel J, Novello S, Ramlau R, Favaretto A, Barlesi F, Akerley W, Orlov S, Santoro A, Spigel D, Hirsh V, Shepherd FA, Sequist LV, Sandler A, Ross JS, Wang Q, von Roemeling R, Shuster D, Schwartz B. Phase III Multinational, Randomized, Double-Blind, Placebo-Controlled Study of Tivantinib (ARQ 197) Plus Erlotinib Versus Erlotinib Alone in Previously Treated Patients With Locally Advanced or Metastatic Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2015 Aug 20;33(24):2667-74. doi: 10.1200/JCO.2014.60.7317. Epub 2015 Jul 13.
PubMed 26169611Scagliotti GV, Novello S, Schiller JH, Hirsh V, Sequist LV, Soria JC, von Pawel J, Schwartz B, Von Roemeling R, Sandler AB. Rationale and design of MARQUEE: a phase III, randomized, double-blind study of tivantinib plus erlotinib versus placebo plus erlotinib in previously treated patients with locally advanced or metastatic, nonsquamous, non-small-cell lung cancer. Clin Lung Cancer. 2012 Sep;13(5):391-5. doi: 10.1016/j.cllc.2012.01.003. Epub 2012 Mar 21.
PubMed 22440336
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT01244191
- Acronym / sponsor ID
- ARQ197-A-U302
- Conditions
- Non Squamous, Non-small-cell Lung Cancer
- Keywords
- Non squamous, non-small-cell lung cancer, Epidermal growth factor receptor, c-Met inhibitor
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision due to the protocol-defined stopping boundary for futility was met based on the interim OS data.
- Enrolment
- 1,048 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Collaborators
- ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
- Study start
- 11 Jan 2011 (actual)
- Primary completion
- 15 Dec 2012 (actual)
- Study completion
- 15 Dec 2012 (actual)
- First posted
- 19 Nov 2010 (estimated)
- Results
- Posted 30 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tivantinib and erlotinib | Experimental | Drug: Tivantinib, Drug: ErlotinibTivantinib 720 mg daily (360 mg twice a day) in combination with 150 mg of erlotinib, given once a day |
| Placebo and erlotinib | Active comparator | Drug: Placebo, Drug: ErlotinibTivantinib placebo given twice a day in combination with 150 mg of erlotinib, given once a day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (14 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TivantinibAlso: ARQ197Tivantinib 720 mg daily as 3 x 120 mg oral tablets given twice a day | Drug | Tivantinib and erlotinib |
| PlaceboAlso: No drugTivantinib Placebo tablets given twice a day | Drug | Placebo and erlotinib |
| ErlotinibErlotinib 150 mg oral tablets, given once a day | Drug | Placebo and erlotinib, Tivantinib and erlotinib |
Primary outcome
Overall Survival Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer
Time frame: Date of randomization up to date of death, up to approximately 1 year 11 months postdose
The overall survival (OS) was defined as the time from the date of randomization to the date of death from any cause.
7 secondary outcomes
Progression-free Survival Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer
Time frame: Date of randomization to disease progression or death (whichever comes first), up to 1 year 11 months postdose
Overall Survival in the Epidermal Growth Factor Receptor Gene Wild-Type Subpopulation Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Non-Squamous NSCLC
Time frame: Date of randomization up to date of death, up to approximately 1 year 11 months postdose
Progression-free Survival in the Epidermal Growth Factor Receptor (EGFR) Gene Wild-Type Subpopulation Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants Non-Squamous NSCLC
Time frame: Date of randomization to disease progression or death (whichever comes first), up to 1 year 11 months postdose
Best Overall Tumor Response Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer
Time frame: From baseline up to disease progression or the development of unacceptable toxicity (whichever occurs first), up to 1 year 11 months postdose
Duration of Response Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer
Time frame: From the date of first objective response (CR or PR) or SD to date of progressive disease, up to 1 year 11 months postdose
Treatment-Emergent Adverse Events Reported in ≥5% of Participants Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Non-Squamous, Non-Small-Cell Lung Cancer
Time frame: Baseline up to 30 days after last dose, up to 1 year 11 months postdose
Treatment-Emergent Adverse Events Related to Tivantinib/Placebo Experienced by ≥5% of Participants Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Non-Squamous NSCLC
Time frame: Baseline up to 30 days after last dose, up to 1 year 11 months postdose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26169611Scagliotti G, von Pawel J, Novello S, Ramlau R, Favaretto A, Barlesi F, Akerley W, Orlov S, Santoro A, Spigel D, Hirsh V, Shepherd FA, Sequist LV, Sandler A, Ross JS, Wang Q, von Roemeling R, Shuster D, Schwartz B. Phase III Multinational, Randomized, Double-Blind, Placebo-Controlled Study of Tivantinib (ARQ 197) Plus Erlotinib Versus Erlotinib Alone in Previously Treated Patients With Locally Advanced or Metastatic Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2015 Aug 20;33(24):2667-74. doi: 10.1200/JCO.2014.60.7317. Epub 2015 Jul 13.
- Derived from this study: PubMed 22440336Scagliotti GV, Novello S, Schiller JH, Hirsh V, Sequist LV, Soria JC, von Pawel J, Schwartz B, Von Roemeling R, Sandler AB. Rationale and design of MARQUEE: a phase III, randomized, double-blind study of tivantinib plus erlotinib versus placebo plus erlotinib in previously treated patients with locally advanced or metastatic, nonsquamous, non-small-cell lung cancer. Clin Lung Cancer. 2012 Sep;13(5):391-5. doi: 10.1016/j.cllc.2012.01.003. Epub 2012 Mar 21.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Leader study director
Daiichi Sankyo
304 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tivantinib and Erlotinib in people with Non Squamous, Non-small-cell Lung Cancer, run by Daiichi Sankyo at 304 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 304 sites in United States, Italy, Germany, Spain, France and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer (time frame: Date of randomization up to date of death, up to approximately 1 year 11 months postdose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01244191, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2021.