Anti-endoglin Chimeric Monoclonal Antibody TRC105 with Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients with Stage IV Lung Cancer

Inclusion Criteria

• Stage 4 non-squamous cell lung cancer that has not been treated previously with systemic chemotherapy or bevacizumab, but may have received prior targeted treatment (e.g., alk1 inhibitor)
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST)
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Resolution of all acute adverse events resulting from prior cancer therapies to National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) grade =< 1 or baseline (except alopecia or neuropathy)
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x upper limit of normal (ULN) or =< 5 x ULN in cases of liver metastases
• Total serum bilirubin =< 1.5 times the upper limit of normal
• Absolute neutrophil count (ANC) >= 1500/μL
• Platelets >= 100,000/μL without transfusion support within the past 28 days
• Hemoglobin >= 9.0 g/dL without transfusion support within the past 28 days (erythropoietin or darbepoetin permitted)
• Serum creatinine =< 1.5 times the upper limit of normal or creatinine clearance > 30 mL/min by Cockcroft-Gault formula
• < 1+ proteinuria
• International normalized ratio (INR) from 0.8 to 1.2
• Willingness and ability to consent for self to participate in study
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
• Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis) or agree to use at least two forms of a reliable and highly effective method of birth control and to not donate sperm and for at least 180 days following last dose of TRC105, bevacizumab, paclitaxel, and/or carboplatin
• Woman of non-child bearing potential due to surgical sterilization (at least 6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history or menopause, OR woman of child bearing potential who test negative for pregnancy at time of enrollment based on serum pregnancy test and agree to use at least 2 forms of a reliable and highly effective method of birth control during the study and for at least 180 days after stopping TRC105, bevacizumab, paclitaxel, and/or carboplatin

Exclusion Criteria

• Non-small cell lung cancer of squamous histology
• Prior treatment with TRC105
• Current treatment on another therapeutic clinical trial
• Receipt of a small molecule anticancer agent, including an investigational anticancer small molecule, within 14 days of starting study treatment
• Receipt of a large molecule anticancer agent (e.g., antibody), including an investigational anticancer antibody, within 28 days of starting study treatment
• No major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure; date of surgery (if applicable) or the anticipated need for a major surgical procedure within the next six months; Note: the following are not considered to be major procedures and are permitted up to 7 days before therapy initiation: thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, tube thoracostomy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies, imaging-guided biopsy for diagnostic purposes, and routine dental procedures
• Patients who have received wide field radiotherapy =< 28 days (defined as > 50% of volume of pelvic bones or equivalent) or limited field radiation for palliation < 14 days prior to study registration or those patients who have not recovered adequately from side effects of such therapy
• Uncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite optimal therapy (initiation or adjustment of blood pressure (BP) medication prior to study entry is allowed provided that the average of 3 BP readings at a visit prior to enrollment is < 140/90 mm Hg)
• History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease; patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for at least 28 days
• Angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass surgery (CABG) within the past 6 months; deep venous thrombosis within 6 months, unless the patient is anticoagulated without the use of warfarin for at least 2 weeks; in this situation, low molecular weight heparin is preferred
• Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia); patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible
• Thrombolytic use (except to maintain i.v. catheters) or anticoagulant use within 10 days prior to first day of study therapy
• Cardiac dysrhythmias of NCI CTCAE grade >= 2 within the last 28 days
• Known active viral or nonviral hepatitis or cirrhosis
• History of hemorrhage or hemoptysis (> 1/2 teaspoon bright red blood) within 3 months of starting study treatment
• History of peptic ulcer disease or erosive gastritis within the past 3 months, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment
• History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved (e.g., through surgical resection or repair)
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study