A Study of Chemotherapy and Ramucirumab Versus Chemotherapy Alone in Second Line Non-Small Cell Lung Cancer (NSCLC) Participants Who Received Prior First Line Platinum-based Chemotherapy
NCT ID: NCT01168973
Last Updated: 2019-09-25
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
1253 participants
INTERVENTIONAL
2010-12-31
2016-08-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Ramucirumab + Docetaxel
Ramucirumab
10 milligrams per kilogram (mg/kg) administered intravenously (IV) on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Docetaxel
75 milligrams per square meter (mg/m\^2) (60 mg/m\^2 for the countries of Korea and Taiwan only with protocol amendment dated 22 May 2012) administered IV on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Placebo + Docetaxel
Placebo (for Ramucirumab)
Administered IV on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Docetaxel
75 milligrams per square meter (mg/m\^2) (60 mg/m\^2 for the countries of Korea and Taiwan only with protocol amendment dated 22 May 2012) administered IV on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Interventions
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Ramucirumab
10 milligrams per kilogram (mg/kg) administered intravenously (IV) on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Placebo (for Ramucirumab)
Administered IV on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Docetaxel
75 milligrams per square meter (mg/m\^2) (60 mg/m\^2 for the countries of Korea and Taiwan only with protocol amendment dated 22 May 2012) administered IV on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Prior bevacizumab as first-line and/or maintenance therapy is allowed
* Signed informed consent
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Histologically or cytologically confirmed NSCLC
* Stage IV NSCLC disease
* Participants have measurable or nonmeasurable disease
* Adequate organ function, defined as:
* Total bilirubin less than or equal to Upper Limit of Normal (ULN),
* Aspartate Aminotransferase (AST) and Alanine Aminotransaminase (ALT) less than or equal to 2.5 x ULN, or less than or equal to 5 x ULN if the transferase elevation is due to liver metastases,
* Serum creatinine less than or equal to 1.5 x ULN or calculated creatinine clearance greater than or equal to 50 milliliters per minute (ml/min) (per the Cockcroft-Gault formula or equivalent and/or 24-hour urine collection),
* Absolute Neutrophil Count (ANC) greater than or equal to 1.5 x 10\^3/microliters (µL), hemoglobin greater than or equal to 10.0 grams/deciliter (g/dL), and platelets greater than or equal to 100 x 10\^3/µL,
* Adequate coagulation function as defined by International Normalized Ratio (INR) less than or equal to 1.5, or prothrombin time and partial thromboplastin time less than or equal to 1.5 x ULN.
* The participant does not have cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis.
* Urinary protein is less than or equal to 1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria greater than or equal to 2+, a 24-hour urine must be collected and must demonstrate less than 1000 milligrams (mg) of protein.
* Participants of reproductive potential (both sexes) must agree to use reliable method of birth control (hormonal or barrier methods) during the study period and at least 12 weeks after the last dose of study therapy
* Life expectancy of greater than or equal to 3 months
* Prior radiation therapy is allowed if: In the case of chest radiotherapy at least 28 days have elapsed from the completion of radiation treatment prior to randomization; In the case of focal or palliative radiation treatment at least 7 days have elapsed from last radiation treatment prior to randomization (and provided that 25% or less of total bone marrow had been irradiated); In the case of Central Nervous System (CNS) radiation at least 14 days have elapsed from the completion of radiation treatment prior to randomization
Exclusion Criteria
* Participants whose only prior treatment was a tyrosine kinase inhibitor
* The participant's tumor wholly or partially contains small cell lung cancer
* Major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization. Postoperative bleeding complications or wound complications from a surgical procedure performed in the last 2 months.
* Concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, chemoembolization, or targeted therapy
* Last dose of bevacizumab must be at least 28 days from time of randomization
* Last dose of cytotoxic chemotherapy must be at least 14 days from time of randomization
* The participant has untreated CNS metastases. Participants with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation ending at least 2 weeks prior to randomization, or after surgical resection performed at least 28 days prior to randomization. No evidence of Grade greater than or equal to 1 CNS hemorrhage based on pretreatment Magnetic Resonance Imaging (MRI) or IV contrast Computed Tomography (CT) scan.
* Radiologically documented evidence of major blood vessel invasion or encasement by cancer
* Radiographic evidence of intratumor cavitation
* History of uncontrolled hereditary or acquired thrombotic disorder
* Chronic therapy with nonsteroidal anti-inflammatory drug (NSAIDs) or other antiplatelet agents; Aspirin use at doses up to 325 milligrams per day (mg/day) is permitted
* History of gross hemoptysis (defined as bright red blood or greater than or equal to 1/2 teaspoon) within 2 months prior to randomization
* Clinically relevant congestive heart failure \[New York Heart Association (NYHA II-IV)\] or symptomatic or poorly controlled cardiac arrhythmia
* Any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization
* Uncontrolled arterial hypertension greater than or equal to 150 / greater than or equal to 90 millimeters of mercury (mm Hg) despite standard medical management
* Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization
* Significant bleeding disorders, vasculitis, or Grade 3/4 gastrointestinal bleeding within 3 months prior to randomization
* Gastrointestinal (GI) perforation and/or fistulae within 6 months prior to randomization
* Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection Crohn's disease, ulcerative colitis, or chronic diarrhea
* Peripheral neuropathy greater than or equal to Grade 2 \[National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.02\]
* Serious illness or medical condition(s) including, but not limited to: Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness; Active or uncontrolled clinically serious infection; Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration
* Known allergy or hypersensitivity reaction to any of the treatment components
* The participant is pregnant or breastfeeding
* Current or recent (within 28 days prior to randomization) treatment with an investigational drug or device that has not received regulatory approval for any indication at the time of randomization, or participation in another interventional clinical trial
* Prior therapy with docetaxel
18 Years
ALL
No
Sponsors
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Eli Lilly and Company
INDUSTRY
Responsible Party
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Principal Investigators
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Role: STUDY_DIRECTOR
Eli Lilly and Company
Locations
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Phoenix, Arizona, United States
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Sedona, Arizona, United States
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Fayetteville, Arkansas, United States
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Alhambra, California, United States
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Duarte, California, United States
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Fresno, California, United States
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Fullerton, California, United States
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La Jolla, California, United States
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Long Beach, California, United States
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Los Angeles, California, United States
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Northridge, California, United States
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Redondo Beach, California, United States
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Santa Barbara, California, United States
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Santa Monica, California, United States
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Denver, Colorado, United States
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Waterbury, Connecticut, United States
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Jacksonville, Florida, United States
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Miami, Florida, United States
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Ocala, Florida, United States
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Orlando, Florida, United States
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Athens, Georgia, United States
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Augusta, Georgia, United States
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Lawrenceville, Georgia, United States
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Macon, Georgia, United States
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Rome, Georgia, United States
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Savannah, Georgia, United States
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Springfield, Illinois, United States
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Bloomington, Indiana, United States
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Cedar Rapids, Iowa, United States
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Iowa City, Iowa, United States
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Overland Park, Kansas, United States
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Wichita, Kansas, United States
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Ashland, Kentucky, United States
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Mount Sterling, Kentucky, United States
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Baton Rouge, Louisiana, United States
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Metairie, Louisiana, United States
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Bethesda, Maryland, United States
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Chevy Chase, Maryland, United States
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Boston, Massachusetts, United States
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Danvers, Massachusetts, United States
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Framingham, Massachusetts, United States
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Newton, Massachusetts, United States
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Ann Arbor, Michigan, United States
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Minneapolis, Minnesota, United States
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Columbia, Missouri, United States
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Joplin, Missouri, United States
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St Louis, Missouri, United States
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Billings, Montana, United States
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Henderson, Nevada, United States
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Reno, Nevada, United States
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Lebanon, New Hampshire, United States
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Portsmouth, New Hampshire, United States
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Albuquerque, New Mexico, United States
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Latham, New York, United States
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New York, New York, United States
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The Bronx, New York, United States
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Durham, North Carolina, United States
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Raleigh, North Carolina, United States
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Fargo, North Dakota, United States
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Columbus, Ohio, United States
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Tulsa, Oklahoma, United States
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Abington, Pennsylvania, United States
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Kingston, Pennsylvania, United States
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Philadelphia, Pennsylvania, United States
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Charleston, South Carolina, United States
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Sioux Falls, South Dakota, United States
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Chattanooga, Tennessee, United States
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Memphis, Tennessee, United States
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Abilene, Texas, United States
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Amarillo, Texas, United States
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Beaumont, Texas, United States
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Bedford, Texas, United States
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Dallas, Texas, United States
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El Paso, Texas, United States
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Fort Worth, Texas, United States
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Lewisville, Texas, United States
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McAllen, Texas, United States
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Mesquite, Texas, United States
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Midland, Texas, United States
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Odessa, Texas, United States
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Paris, Texas, United States
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San Antonio, Texas, United States
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San Antonio, Texas, United States
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Sherman, Texas, United States
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Sugar Land, Texas, United States
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The Woodlands, Texas, United States
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Tyler, Texas, United States
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Webster, Texas, United States
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Wichita Falls, Texas, United States
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Christiansburg, Virginia, United States
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Fairfax, Virginia, United States
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Newport News, Virginia, United States
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Richmond, Virginia, United States
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Lacey, Washington, United States
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Spokane, Washington, United States
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Wenatchee, Washington, United States
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Madison, Wisconsin, United States
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Buenos Aires, , Argentina
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Córdoba, , Argentina
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La Rioja, , Argentina
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Rosario, , Argentina
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Tucumain, , Argentina
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Viedma, , Argentina
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Graz, , Austria
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Grimmenstein, , Austria
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Vienna, , Austria
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Wels, , Austria
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Barretos, , Brazil
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Belo Horizonte, , Brazil
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Goiânia, , Brazil
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Porto Alegre, , Brazil
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São Paulo, , Brazil
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Edmonton, Alberta, Canada
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Moncton, New Brunswick, Canada
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Sainte-Foy, Quebec, Canada
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Grenoble, , France
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Lille, , France
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Lyon, , France
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Nice, , France
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Strasbourg, , France
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Toulouse, , France
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Vandœuvre-lès-Nancy, , France
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Augsburg, , Germany
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Bad Soden, , Germany
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Bielefeld, , Germany
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Dresden, , Germany
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Frankfurt, , Germany
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Gerlingen, , Germany
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Großhansdorf, , Germany
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Halle, , Germany
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Heidelberg, , Germany
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Immenhausen, , Germany
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Oldenburg, , Germany
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Ulm, , Germany
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Villingen-Schwenningen, , Germany
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Athens, , Greece
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Chania, , Greece
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Kifissia, , Greece
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Pátrai, , Greece
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Budapest, , Hungary
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Gyula, , Hungary
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Mátraháza, , Hungary
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Nyíregyháza, , Hungary
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Pécs, , Hungary
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Székesfehérvár, , Hungary
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Bangalore, , India
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Cuttack, , India
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Delhi, , India
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Jaipur, , India
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Kochi, , India
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Madurai, , India
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Mumbai, , India
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Pune, , India
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Trivandrum, , India
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Haifa, , Israel
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Jerusalem, , Israel
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Kfar Saba, , Israel
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Petah Tikva, , Israel
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Safed, , Israel
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Tel Aviv, , Israel
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Livorno, , Italy
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Monza, , Italy
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Novara, , Italy
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Padua, , Italy
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Palermo, , Italy
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Parma, , Italy
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Pisa, , Italy
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Rome, , Italy
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Guadalajara, , Mexico
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Mexico City, , Mexico
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's-Hertogenbosch, , Netherlands
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Amsterdam, , Netherlands
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Arnhem, , Netherlands
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Harderwijk, , Netherlands
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Zwolle, , Netherlands
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Grafton, , New Zealand
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Wellington, , New Zealand
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Oslo, , Norway
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Tromsø, , Norway
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Gdansk, , Poland
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Gdynia, , Poland
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Głuchołazy, , Poland
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Krakow, , Poland
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Lodz, , Poland
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Opole, , Poland
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Otwock, , Poland
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Poznan, , Poland
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Bayamón, , Puerto Rico
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Bucharest, , Romania
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Cluj-Napoca, , Romania
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Iași, , Romania
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Moscow, , Russia
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Saint Petersburg, , Russia
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Stavropol, , Russia
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Incheon, , South Korea
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Seoul, , South Korea
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Suwon, , South Korea
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Barcelona, , Spain
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Girona, , Spain
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Las Palmas de Gran Canaria, , Spain
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Madrid, , Spain
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Mataró, , Spain
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Pamplona, , Spain
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Pozuelo de Alarcón, , Spain
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Eskilstuna, , Sweden
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Linköping, , Sweden
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Lund, , Sweden
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Solna, , Sweden
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Basel, , Switzerland
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Bern, , Switzerland
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Fribourg, , Switzerland
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Lucerne, , Switzerland
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Zurich, , Switzerland
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Kaohsiung City, , Taiwan
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Kuei Shan Hsiang, , Taiwan
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Neihu Taipei, , Taiwan
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Niao Sung Hsiang, , Taiwan
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Taichung, , Taiwan
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Taipei, , Taiwan
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Ankara, , Turkey (Türkiye)
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Istanbul, , Turkey (Türkiye)
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Izmir, , Turkey (Türkiye)
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Kayseri, , Turkey (Türkiye)
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Cottingham, East Yorkshire, United Kingdom
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London, Greater London, United Kingdom
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Preston, Lancashire, United Kingdom
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Wythenshawe, Manchester, United Kingdom
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Scunthorpe, North Lincolnshire, United Kingdom
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Glasgow, Scotland, United Kingdom
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Coventry, West Midlands, United Kingdom
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Wolverhampton, West Midlands, United Kingdom
Countries
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References
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Rolfo C, Hess LM, Jen MH, Peterson P, Li X, Liu H, Lai Y, Sugihara T, Kiiskinen U, Vickers A, Summers Y. External control cohorts for the single-arm LIBRETTO-001 trial of selpercatinib in RET+ non-small-cell lung cancer. ESMO Open. 2022 Aug;7(4):100551. doi: 10.1016/j.esmoop.2022.100551. Epub 2022 Aug 2.
Garon EB, Scagliotti GV, Gautschi O, Reck M, Thomas M, Iglesias Docampo L, Kalofonos H, Kim JH, Gans S, Brustugun OT, Orlov SV, Cuyun Carter G, Zimmermann AH, Oton AB, Alexandris E, Lee P, Wolff K, Stefaniak VJ, Socinski MA, Perol M. Exploratory analysis of front-line therapies in REVEL: a randomised phase 3 study of ramucirumab plus docetaxel versus docetaxel for the treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy. ESMO Open. 2020 Jan;5(1):e000567. doi: 10.1136/esmoopen-2019-000567.
Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Perol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23;384(9944):665-73. doi: 10.1016/S0140-6736(14)60845-X. Epub 2014 Jun 2.
Garon EB, Cao D, Alexandris E, John WJ, Yurasov S, Perol M. A randomized, double-blind, phase III study of Docetaxel and Ramucirumab versus Docetaxel and placebo in the treatment of stage IV non-small-cell lung cancer after disease progression after 1 previous platinum-based therapy (REVEL): treatment rationale and study design. Clin Lung Cancer. 2012 Nov;13(6):505-9. doi: 10.1016/j.cllc.2012.06.007. Epub 2012 Jul 31.
Other Identifiers
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I4T-MC-JVBA
Identifier Type: OTHER
Identifier Source: secondary_id
2010-021297-11
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CP12-1027
Identifier Type: OTHER
Identifier Source: secondary_id
CTRI/2011/08/001942
Identifier Type: REGISTRY
Identifier Source: secondary_id
13852
Identifier Type: -
Identifier Source: org_study_id
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