A Study of Ramucirumab (IMC-1121B) With Paclitaxel and Carboplatin in Non-small Cell Lung Cancer

A Phase 2, Open-label Study of IMC-1121B in Combination With Paclitaxel and Carboplatin as First-line Therapy in Patients With Stage IIIB/IV Non-small Cell Lung Cancer

The purpose of this study is to evaluate the progression-free survival (PFS) rate at 6 months of ramucirumab administered in combination with paclitaxel and carboplatin as first-line therapy for Stage IIIB or IV non-small cell lung cancer

Non-small cell lung cancer (NSCLC) accounts for 75-80% of all lung cancers. The advanced stages are associated with poor survival rates, a median survival rate of approximately 3.9 months if left untreated.

Angiogenesis is a process for wound healing and restoring blood flow to tissues after injury. It is the physiological process involving the growth of new blood vessels from pre-existing vessels. Angiogenesis may be promoted by growth factors and in diseases such as cancer, where growth factors are over expressed, the body loses the ability to maintain a balanced angiogenesis. This may embellish the existing supplies of blood; potentially increasing the delivery of oxygen and nutrients supplies for cancer growth and survival.

Ramucirumab is an angiogenesis inhibitor; and is believed to block the promotion of the growth factor to form new blood vessels, thus reducing the blood supply to the cancer cells.

Inclusion Criteria:

• Histologically or cytologically confirmed NSCLC
• Advanced NSCLC
• Measurable disease (as defined by Response Evaluation Criteria in Solid Tumors [RECIST 1.0])
• Eastern Cooperative Oncology Group (ECOG) Performance Status is ≤ 1
• Age ≥ 18 years
• Adequate hematologic function = an absolute neutrophil count (ANC) ≥ 1500/μL, hemoglobin ≥ 9 g/dL, and a platelet count ≥ 100,000/microliter (μL)
• Adequate hepatic function = a total bilirubin ≤ 1.5 mg/dL transaminases and alkaline phosphatase ≤ 5 x the upper limit of normal (ULN)
• Adequate renal function serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCl) > 60 mL/minute, and urine dipstick for protein < 1+ (ie, either 0 or trace)
• Adequate coagulation function, INR ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above ULN
• Adequate contraception
• Signed informed consent

Exclusion Criteria:

• Untreated CNS metastases
• Prior bevacizumab therapy
• Radiologically documented evidence of major blood vessel invasion or encasement by cancer
• Prior systemic chemotherapy for Stage IIIB/IV NSCLC
• Prior systemic chemotherapy or radiation therapy for Stage I-IIIA NSCLC < 1 year prior
• Any concurrent malignancy other than basal cell skin cancer, or carcinoma in situ of the cervix
• Concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy
• 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
• Uncontrolled thrombotic or hemorrhagic disorders
• Poorly-controlled hypertension
• Chronic daily treatment with aspirin (> 325 mg/day) or other known inhibitors of platelet function
• History of gross hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon)
• Serious non-healing wound, ulcer, or bone fracture
• Undergone major surgery or subcutaneous venous access device placement. Post-operative bleeding complications or wound complications from a surgical procedures performed in the last 2 months
• Elective or a planned major surgery to be performed during the course of the trial
• Peripheral neuropathy ≥ Grade 2 (National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 3.0 [NCI-CTCAE v 3.0])
• If female, is pregnant or lactating
• Radiographic evidence of intratumor cavitation
• Grade 3-4 gastrointestinal bleeding within 3 months prior to study entry