Combination Chemotherapy with or without Ramucirumab in Treating Patients with Metastatic or Recurrent Pancreatic Cancer

Inclusion Criteria

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information; Note: HIPAA authorization may be included in the informed consent or obtained separately
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 7 days prior to registration
• Histologic or cytological diagnosis of recurrent or metastatic pancreas adenocarcinoma (PCA) who present for first line chemotherapy treatment
• No prior first line systemic treatment (prior adjuvant or neoadjuvant treatment is permitted); subjects whose disease has progressed after 6 months of last systemic chemotherapy or chemo-radiation in the adjuvant or neoadjuvant setting are eligible
• Measurable disease determined using guidelines of Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; baseline tumor assessment should be performed using high resolution computed tomography (CT) scans or magnetic resonance imaging (MRI)
• Urine protein < 1+ on dipstick test or routine urinalysis; if the proteinuria on these tests is >= 2+, then a 24-hour urine test must be collected and must demonstrate < 1 g protein in 24 hours to allow participation
• Estimated life expectancy of > 12 weeks, as assessed by the site investigator
• If sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods)
• Hemoglobin >= 9 g/dL
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count (PLT) >= 100,000/mm^3
• Creatinine =< 1.5 mg/dL or creatinine clearance >= 40 mL/min * If serum creatinine is > 1.5 times the upper limit of normal (ULN), a 24-hour urine collection to calculate creatinine clearance must be performed
• Albumin >= 2.5 g/dL
• Bilirubin =< 1.5 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN or < 5 x ULN in the setting of liver metastases
• The subject has adequate coagulation function as defined by international normalized ratio (INR) =< 1.5 and a partial thromboplastin time (PTT) (PTT/aPTT) < 1.5 x ULN * Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy

Exclusion Criteria

• Subjects with histology other than adenocarcinoma; examples include: neuroendocrine tumors, acinar cell cancer, sarcoma or lymphoma of the pancreas
• Ongoing or active infection
• Symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia; symptomatic heart failure (New York Heart Association [NYHA] class II-IV)
• Uncontrolled or poorly-controlled hypertension (> 160 mmHg systolic or > 100 mmHg diastolic for > 4 weeks) despite standard medical management
• Acute or sub-acute intestinal obstruction
• Interstitial pneumonia or interstitial fibrosis of the lung, which in the opinion of the site investigator could compromise the subject or the study
• Pleural effusion or ascites that causes > grade 1 dyspnea
• Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) with a history of hepatic encephalopathy or clinical meaningful ascites resulting from cirrhosis; clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
• Grade 3 or higher bleeding event =< 3 months prior to randomization
• Experience of any arterial thrombotic or arterial thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident, =< 6 months prior to randomization
• History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered “significant”) during the 3 months prior to randomization
• Gastrointestinal (GI) perforation/fistula
• Documented and/or symptomatic or known brain or leptomeningeal metastases
• Severely immune-compromised (other than being on steroids) including known human immunodeficiency virus (HIV) infection
• Concurrent active malignancy, other than adequately treated non-melanoma skin cancer, other noninvasive carcinoma, or in situ neoplasm; a subject with previous history of malignancy is eligible, provided that he/she has been disease-free for > 3 years
• Breast-feeding or pregnant; serum pregnancy test for women of child-bearing potential must be performed within 7 days prior to first dose of study treatment
• Prior autologous or allogeneic organ or tissue transplantation
• Known allergy to any of the treatment components
• The patient has undergone major surgery within 28 days prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 2 days prior to first dose of protocol therapy; the patient has elective or planned major surgery to be performed during the course of the clinical trial
• Have any condition that does not permit compliance with the study schedule including psychological, geographical, or medical
• Receiving medications that can effect clotting ability: warfarin, aspirin, (once-daily aspirin use- maximum dose 325 mg/day is permitted), nonsteroidal anti-inflammatory drugs (nonsteroidal antiinflammatory drug [NSAID]s, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents
• The patient has a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy