Ramucirumab and Nab-Paclitaxel in Treating Patients with Previously Treated Stage IV Non-small Cell Lung Cancer

Inclusion Criteria

• Patients must have histologically or cytologically confirmed stage IV (American Joint Committee on Cancer [AJCC] 7) non-small cell lung cancer
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Patients must have received at least one prior platinum-based chemotherapy for locally advanced or metastatic disease; prior bevacizumab as 1st line and/or maintenance therapy is allowed; prior nivolumab is allowed
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy of greater than 12 weeks
• Total bilirubin =< 1.5 mg/dL (25.65 umol/L)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) or 5.0 x upper limit of normal (ULN) in the setting of liver metastases
• Absolute neutrophil count (ANC) >= 1500/uL
• Hemoglobin >= 9 g/dL (5.58 mmol/L)
• Platelets >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within 7 days prior to laboratory sample)
• The patient 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 from cirrhosis requiring diuretics or paracentesis
• Serum creatinine =< 1.5 times the ULN, or calculated creatinine clearance >= 50 mL/minute (per the Cockcroft-Gault formula)
• The patient’s urinary protein is =< 1+ on dipstick or routine urinalysis (urine analysis [UA]; if urine dipstick or routine analysis is >= 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in this protocol)
• International normalized ratio (INR) =< 1.5 or prothrombin time (PT) =< 1.5 ULN, and a partial thromboplastin time (PTT/activated partial thromboplastin time [aPTT]) =< 1.5 x ULN
• Patients with treated and clinically stable brain metastases are allowed
• Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; females of child-bearing potential (defined as a sexually mature woman who [1] has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or [2] has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must: * Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting investigational product (IP) therapy (including dose interruptions), and while on study medication or for a longer period if required by local regulations following the last dose of IP; and * Have a negative serum pregnancy test (beta-human chorionic gonadotropin [hCG]) result at screening; this applies even if the subject practices true abstinence from heterosexual contact ** True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception])
• Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following IP discontinuation, even if he has undergone a successful vasectomy
• Patients must have < grade 2 pre-existing peripheral neuropathy (per Common Terminology Criteria for Adverse Events [CTCAE])
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients previously treated with taxanes are excluded, unless the taxane therapy was part of an initially curative regimen (e.g. adjuvant) and was completed > 12 months from study enrollment; patients with previous intolerance to ramucirumab
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ramucirumab or nab-paclitaxel
• Patients with untreated central nervous system (CNS) metastases; patients with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiotherapy, focal radiotherapy, and stereotactic radiosurgery) ending at least 2 weeks prior to randomization, or after surgical resection performed at least 28 days prior to randomization; the patient may have no evidence of grade >= 1 CNS hemorrhage based on pretreatment MRI or IV contrast CT scan (performed within 21 days before randomization)
• The patient has significant bleeding disorders, vasculitis, or experienced grade 3/4 gastrointestinal (GI) bleeding within 3 months prior to enrollment
• The patient has a 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
• The patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrollment
• The patient has a history of uncontrolled hereditary or acquired thrombotic disorder
• The patient has uncontrolled or poorly-controlled hypertension (>= 150 / >= 90 mm Hg) despite standard medical management
• The patient has a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to enrollment
• The patient has undergone major surgery within 28 days prior to enrollment, or subcutaneous venous access device placement within 7 days prior to enrollment
• The patient is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal antiinflammatory drugs (non-steroidal anti-inflammatory drug [NSAIDs], including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents; once-daily aspirin use (maximum dose 325 mg/day) is permitted
• The patient has elective or planned major surgery to be performed during the course of the clinical trial
• Patients with hemoptysis (defined as bright red blood or >= 1/2 teaspoon) within 2 months prior to enrollment, or with central or cavitating lesions, will be excluded
• The patient has radiologically documented evidence of major blood vessel invasion or encasement by cancer
• The patient has a history of GI perforation and/or fistulae within 6 months prior to enrollment
• The patient is receiving therapeutic anticoagulation with warfarin, low molecular weight heparin, or similar agents; patients receiving prophylactic, low-dose anticoagulation therapy are eligible provided that the coagulation parameters defined in the inclusion criteria (INR =< 1.5 or PT =< 1.5 x ULN and PTT/aPTT =< 1.5 x ULN)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ramucirumab; these potential risks may also apply to other agents used in this study
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible