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
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Ramucirumab; Placebo (for Ramucirumab); Docetaxel
Intervention description: 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; Administered IV on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met; 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
Intervention MeSH terms: Docetaxel; Ramucirumab; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1253.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: second line; non small cell lung cancer; NSCLC; phase 3; ramucirumab; lung cancer; docetaxel; taxotere

Summary:

      The purpose of the study is to compare the survival of participants who receive chemotherapy
      and ramucirumab versus chemotherapy alone as second line treatment for NSCLC after prior
      first line platinum-based chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Disease progression during or after one prior first-line platinum-based chemotherapy
             with or without maintenance therapy

          -  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:

          -  Disease progression on more than 1 prior chemotherapy regimens

          -  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