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

NCT ID: NCT01244191

Last Updated: 2021-04-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1048 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-11
• Study Completion Date: 2012-12-15

Brief 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.

Conditions

Non Squamous, Non-small-cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Tivantinib and erlotinib

Tivantinib 720 mg daily (360 mg twice a day) in combination with 150 mg of erlotinib, given once a day

Group Type: EXPERIMENTAL

Tivantinib

Intervention Type: DRUG

Tivantinib 720 mg daily as 3 x 120 mg oral tablets given twice a day

Erlotinib

Intervention Type: DRUG

Erlotinib 150 mg oral tablets, given once a day

Placebo and erlotinib

Tivantinib placebo given twice a day in combination with 150 mg of erlotinib, given once a day

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DRUG

Tivantinib Placebo tablets given twice a day

Erlotinib

Intervention Type: DRUG

Erlotinib 150 mg oral tablets, given once a day

Interventions

Tivantinib

Tivantinib 720 mg daily as 3 x 120 mg oral tablets given twice a day

Intervention Type: DRUG

Placebo

Tivantinib Placebo tablets given twice a day

Intervention Type: DRUG

Erlotinib

Erlotinib 150 mg oral tablets, given once a day

Intervention Type: DRUG

Other Intervention Names

ARQ197; No drug

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)

INDUSTRY

Sponsor Role: collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Tucson, Arizona, United States

Tucson, Arizona, United States

Tucson, Arizona, United States

Tucson, Arizona, United States

Los Angeles, California, United States

Oxnard, California, United States

Rancho Mirage, California, United States

Rancho Mirage, California, United States

Santa Monica, California, United States

Aurora, Colorado, United States

Boulder, Colorado, United States

Colorado Springs, Colorado, United States

Colorado Springs, Colorado, United States

Denver, Colorado, United States

Denver, Colorado, United States

Lakewood, Colorado, United States

Littleton, Colorado, United States

Lone Tree, Colorado, United States

Longmont, Colorado, United States

Parker, Colorado, United States

Thornton, Colorado, United States

Newark, Delaware, United States

Fort Myers, Florida, United States

Miami Beach, Florida, United States

Pensacola, Florida, United States

Atlanta, Georgia, United States

Austell, Georgia, United States

Carrollton, Georgia, United States

Cartersville, Georgia, United States

Douglasville, Georgia, United States

Marietta, Georgia, United States

Chicago, Illinois, United States

Carmel, Indiana, United States

Fishers, Indiana, United States

Goshen, Indiana, United States

Greenfield, Indiana, United States

Indianapolis, Indiana, United States

Indianapolis, Indiana, United States

Indianapolis, Indiana, United States

Lexington, Kentucky, United States

Louisville, Kentucky, United States

Towson, Maryland, United States

Boston, Massachusetts, United States

Minneapolis, Minnesota, United States

St Louis, Missouri, United States

Grand Island, Nebraska, United States

Omaha, Nebraska, United States

Henderson, Nevada, United States

Henderson, Nevada, United States

Las Vegas, Nevada, United States

Las Vegas, Nevada, United States

Las Vegas, Nevada, United States

East Orange, New Jersey, United States

Albuquerque, New Mexico, United States

Buffalo, New York, United States

Goshen, New York, United States

Latham, New York, United States

New York, New York, United States

The Bronx, New York, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Kettering, Ohio, United States

Eugene, Oregon, United States

Portland, Oregon, United States

Portland, Oregon, United States

Portland, Oregon, United States

Portland, Oregon, United States

Springfield, Oregon, United States

Tualatin, Oregon, United States

Harrisburg, Pennsylvania, United States

Hershey, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Columbia, South Carolina, United States

Easley, South Carolina, United States

Greenville, South Carolina, United States

Greenville, South Carolina, United States

Greenville, South Carolina, United States

Spartanburg, South Carolina, United States

Bartlett, Tennessee, United States

Chattanooga, Tennessee, United States

Germantown, Tennessee, United States

Knoxville, Tennessee, United States

Memphis, Tennessee, United States

Nashville, Tennessee, United States

Southaven, Tennessee, United States

Austin, Texas, United States

Austin, Texas, United States

Austin, Texas, United States

Austin, Texas, United States

Cedar Park, Texas, United States

Dallas, Texas, United States

Dallas, Texas, United States

Fort Worth, Texas, United States

Fort Worth, Texas, United States

Kyle, Texas, United States

Round Rock, Texas, United States

Round Rock, Texas, United States

San Marcos, Texas, United States

Salt Lake City, Utah, United States

Arlington, Virginia, United States

Fairfax, Virginia, United States

Gainesville, Virginia, United States

Leesburg, Virginia, United States

Midlothian, Virginia, United States

Richmond, Virginia, United States

Winchester, Virginia, United States

Woodbridge, Virginia, United States

Seattle, Washington, United States

Vancouver, Washington, United States

Vancouver, Washington, United States

Yakima, Washington, United States

Rosario, Santa Fe Province, Argentina

Buenos Aires, , Argentina

Córdoba, , Argentina

San Miguel de Tucumán, , Argentina

Viedma, , Argentina

Greenslopes, Queensland, Australia

Camperdown, , Australia

Kogarah, , Australia

Perth, , Australia

St Leonards, , Australia

Wollongong, , Australia

Woodville, , Australia

Salzburg, , Austria

Wels, , Austria

Brasschaat, , Belgium

Brussels, , Belgium

Duffel, , Belgium

Salvador, Estado de Bahia, Brazil

Rio de Janeiro, Rio de Janeiro, Brazil

Passo Fundo, Rio Grande do Sul, Brazil

Passo Fundo, Rio Grande do Sul, Brazil

Porto Alegre, Rio Grande do Sul, Brazil

Joinville, Santa Catarina, Brazil

Joinville, Santa Catarina, Brazil

Ijuí, , Brazil

Porto Alegre, , Brazil

São Paulo, , Brazil

São Paulo, , Brazil

Edmonton, Alberta, Canada

Surrey, British Columbia, Canada

Victoria, British Columbia, Canada

Winnipeg, Manitoba, Canada

London, Ontario, Canada

Thunder Bay, Ontario, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Montreal, , Canada

Québec, , Canada

Toronto, , Canada

Santiago, , Chile

Santiago, , Chile

Santiago, , Chile

Santiago, , Chile

Ostrava, , Czechia

Pardubice, , Czechia

Prague, , Czechia

Ústí nad Labem, , Czechia

Herlev, , Denmark

Næstved, , Denmark

Odense, , Denmark

Besançon, , France

Brest, , France

Caen, , France

Grenoble, , France

Lille, , France

Marseille, , France

Paris, , France

Paris, , France

Pierre-Bénite, , France

Rennes, , France

Saint-Priest-en-Jarez, , France

Strasbourg, , France

Toulouse, , France

Tours, , France

Villejuif, , France

Bad Berka, , Germany

Berlin, , Germany

Berlin, , Germany

Cologne, , Germany

Erfurt, , Germany

Essen, , Germany

Esslingen am Neckar, , Germany

Gauting, , Germany

Großhansdorf, , Germany

Halle, , Germany

Hamburg, , Germany

Hanover, , Germany

Karlsruhe, , Germany

Kassel, , Germany

Leverkusen, , Germany

Löwenstein, , Germany

Mainz, , Germany

Mannheim, , Germany

München, , Germany

München, , Germany

München, , Germany

Porta Westfalica, , Germany

Rheine, , Germany

Villingen-Schwenningen, , Germany

Deszk, , Hungary

Gyula, , Hungary

Mátraháza, , Hungary

Székesfehérvár, , Hungary

Szolnok, , Hungary

Ancona, , Italy

Avellino, , Italy

Aviano, , Italy

Bari, , Italy

Catania, , Italy

Cremona, , Italy

Cuneo, , Italy

Florence, , Italy

Livorno, , Italy

Milan, , Italy

Modena, , Italy

Monza, , Italy

Napoli, , Italy

Novara, , Italy

Orbassano, , Italy

Padua, , Italy

Palermo, , Italy

Parma, , Italy

Perugia, , Italy

Roma, , Italy

Rozzano, , Italy

Sassari, , Italy

Sondalo, , Italy

Sora, , Italy

Torino, , Italy

Mexico City, Mexico City, Mexico

Monterrey, Nuevo León, Mexico

Guadalajara, , Mexico

Mexico City, , Mexico

Oaxaca City, , Mexico

Oaxaca City, , Mexico

Enschede, ER, Netherlands

Helmond, HA, Netherlands

Amsterdam, , Netherlands

Arequipa, , Peru

Lima, , Peru

Lima, , Peru

Lima, , Peru

Lima, , Peru

Bystra, , Poland

Krakow, , Poland

Lublin, , Poland

Olsztyn, , Poland

Opole, , Poland

Poznan, , Poland

Poznan, , Poland

Prabuty, , Poland

Rzeszów, , Poland

Szczecin, , Poland

Torun, , Poland

Wałbrzych, , Poland

Cluj-Napoca, , Romania

Craiova, , Romania

Oradea, , Romania

Chelyabinsk, , Russia

Irkutsk, , Russia

Izhevsk, , Russia

Kursk, , Russia

Moscow, , Russia

Moscow, , Russia

Novosibirsk, , Russia

Pyatigorsk, , Russia

Saint Petersburg, , Russia

Saint Petersburg, , Russia

Saint Petersburg, , Russia

Tula, , Russia

Tyumen, , Russia

Veliky Novgorod, , Russia

Barakaldo, Bilbao, Spain

Vigo, Pontevedra, Spain

A Coruña, , Spain

A Coruña, , Spain

Alicante, , Spain

Barcelona, , Spain

Barcelona, , Spain

Madrid, , Spain

Madrid, , Spain

Madrid, , Spain

Manresa, , Spain

Málaga, , Spain

Oviedo, , Spain

Palma de Mallorca, , Spain

Sabadell, , Spain

San Cristóbal de La Laguna, , Spain

Santiago de Compostela, , Spain

Seville, , Spain

Seville, , Spain

Valencia, , Spain

Zaragoza, , Spain

Linköping, , Sweden

Lund, , Sweden

Guildford, Surrey, United Kingdom

Aberdeen, , United Kingdom

Glasgow, , United Kingdom

London, , United Kingdom

London, , United Kingdom

Manchester, , United Kingdom

Nottingham, , United Kingdom

Sheffield, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Canada; Chile; Czechia; Denmark; France; Germany; Hungary; Italy; Mexico; Netherlands; Peru; Poland; Romania; Russia; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 26169611 (View on PubMed)

Scagliotti 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.

Reference Type: DERIVED

PMID: 22440336 (View on PubMed)

Other Identifiers

2010-022365-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ARQ197-A-U302

Identifier Type: -

Identifier Source: org_study_id