A Study of Pemetrexed and Carboplatin/Cisplatin or Gemcitabine and Carboplatin/Cisplatin With or Without IMC-1121B in Participants Previously Untreated With Recurrent or Advanced Non-Small Cell Lung Cancer (NSCLC)
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: IMC-1121B (ramucirumab); Pemetrexed; Carboplatin (AUC 6); Cisplatin; Gemcitabine; Carboplatin (AUC 5)
Intervention description: 10 milligrams/kilogram (mg/kg) once every 3 weeks beginning Day 1, Cycle 1; 500 milligrams/square meter (mg/m²) on Day 1 of every 21-day cycle; Day 1 of every 21-day cycle; 75 mg/m² intravenous (IV) on Day 1 of each 21-day cycle; 1000 mg/m² on Days 1 and 8 of every 21-day cycle; Day 1 of every 21-day cycle
Intervention MeSH terms: Carboplatin; Gemcitabine; Pemetrexed; Ramucirumab; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 280.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lung neoplasms; Lung cancer; Non-small Cell Lung Cancer; pemetrexed; squamous; nonsquamous

Summary:

      The purpose of this study is to determine if participants with Stage IV NSCLC have a better
      outcome when treated with IMC-1121B in combination with pemetrexed + carboplatin/cisplatin or
      gemcitabine + carboplatin/cisplatin than when treated with pemetrexed + carboplatin/cisplatin
      or gemcitabine + carboplatin/cisplatin alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed NSCLC

          -  Stage IV disease at the time of study entry

          -  Measurable disease at the time of study entry

          -  Resolution to Grade ≤ 1 Adverse Events, of all clinically significant toxic effects of
             prior chemotherapy, surgery, radiotherapy, or hormonal therapy (except alopecia)

          -  Adequate hematologic function, hepatic function, renal function and coagulation
             function

          -  If sexually active, must be post-menopausal, surgically sterile, or using effective
             contraception; and agrees to use adequate contraception during the study period and
             for up to 6 months after the last dose of study medication

          -  Female participants of childbearing potential must have a negative serum pregnancy
             test

        Exclusion Criteria:

          -  Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis and a history of
             hepatic encephalopathy, or ascites resulting from cirrhosis and requiring ongoing
             treatment with diuretics and/or paracentesis

          -  Tumor wholly or partially contains small cell lung cancer

          -  Untreated central nervous system (CNS) metastases, eligible if they are clinically
             stable with regard to neurologic function, off all steroids after cranial irradiation
             at least 2 weeks prior or after surgical resection performed at least 4 weeks prior to
             randomization

          -  Concurrent active malignancy other than adequately treated basal cell carcinoma of the
             skin or pre-invasive carcinoma of the cervix. A participant with previous history of
             malignancy other than NSCLC is eligible, provided that he/she has been free of disease
             for ≥ 3 years

          -  Received prior therapy with monoclonal antibodies, signal transduction inhibitors, or
             any therapies targeting the vascular endothelial growth factor (VEGF) or vascular
             endothelial growth factor receptor (VEGFR)

          -  Receiving concurrent treatment with other anticancer therapy

          -  Has received previous chemotherapy for Stage IV NSCLC (participants who have received
             adjuvant chemotherapy are eligible if the last administration of the prior adjuvant
             regimen occurred at least 6 months prior to randomization)

          -  Has radiologically documented evidence of major blood vessel invasion or encasement by
             cancer

          -  Has undergone chest irradiation within 12 weeks prior to randomization (except
             palliative irradiation of bone lesions)

          -  Ongoing or active infection

          -  History of significant neurological or psychiatric disorders

          -  Experienced clinically relevant coronary artery disease, myocardial infarction within
             6 months prior to randomization, uncontrolled congestive heart failure, or symptomatic
             poorly controlled arrhythmia

          -  Poorly-controlled hypertension

          -  Experienced any serious Grade 3-4 gastrointestinal bleeding within 3 months prior to
             study entry

          -  Receiving chronic daily treatment with aspirin (> 325 mg/day) or other known
             inhibitors of platelet function

          -  Serious nonhealing wound, ulcer, or bone fracture within 28 days prior to
             randomization

          -  Major surgery within 28 days prior the first dose of study medication, or subcutaneous
             venous access device placement within 7 days prior to randomization

          -  Elective or a planned major surgery

          -  Pregnant or lactating

          -  Any other serious uncontrolled medical disorders or psychological conditions

          -  Allergy / history of hypersensitivity reaction to any of the treatment components

          -  History of drug abuse