Clinical Trial of the Safety and Efficacy of the Addition of Ramucirumab to Nab-paclitaxel in Previously Treated Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: ramucirumab; nab-paclitaxel
Intervention description: it is administered through a vein in the arm as a 60 minute infusion at a dose of 8 mg/kg on days 1 and 15 of a 28-day cycle.; it is administered through a vein in the arm as a 30 minute infusion at a dose of 100 mg/m2 on days 1, 8 and 15 of a 28 day cycle.
Intervention MeSH terms: Paclitaxel; Ramucirumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ramucirumab; docetaxel

Summary:

      The subjects who take part in this clinical research study have advanced non-small cell lung
      cancer (NSCLC) that has been previously treated with other drugs. If they join this study,
      they would receive ramucirumab (Cyramza ®) in combination with nab-paclitaxel (Abraxane®).
      Ramucirumab given with nab-paclitaxel is considered an investigational drug combination to
      use in this type of cancer because giving these two drugs together has not been approved by
      any regulatory authority like the US Food and Drug Administration (FDA) for NSCLC cancer.
      Ramucirumab works by slowing or stopping the growth of cancer cells. Nab-Paclitaxel works by
      blocking the ability of cancer cells to break down the internal 'skeleton' that allows them
      to divide and multiply. With the skeleton still in place, the cells cannot divide and they
      eventually die.
    

Eligibility criteria:

        Inclusion Criteria:

        All patients must have or meet the following:

          -  Histologically or cytologically confirmed Stage IV (AJCC 7) non-small cell lung
             cancer.

          -  Measurable disease, defined as at least one lesion that can be accurately measured in
             at least one dimension as ≥20 mm with conventional techniques or as ≥10 mm with spiral
             CT scan, MRI, or calipers by clinical exam.

          -  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.

          -  Age ≥18 years.

          -  ECOG performance status ≤2

          -  Life expectancy of greater than 12 weeks.

          -  Adequate liver function

          -  Adequate hematologic function

          -  Not have cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree)
             with a history of hepatic encephalopathy or clinically meaningful ascites resulting
             from cirrhosis.

          -  Adequate renal function

          -  Urinary protein of ≤1+ on dipstick or routine urinalysis (UA).

          -  Adequate coagulation function. Patients receiving warfarin must be switched to low
             molecular weight heparin and have achieved stable coagulation profile prior to first
             dose of protocol therapy.

          -  Treated and clinically stable brain metastases are allowed.

          -  Adequate contraceptive use.

          -  < Grade 2 pre-existing peripheral neuropathy.

          -  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 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 CNS metastases.

          -  Patients with significant bleeding disorders, vasculitis, or who experienced Grade 3/4
             gastrointestinal (GI) bleeding within 3 months prior to enrollment.

          -  History of deep vein thrombosis, pulmonary embolism, or any other significant
             thromboembolism during the 3 months prior to enrollment.

          -  Any arterial thromboembolic events, within 6 months prior to enrollment.

          -  History of uncontrolled hereditary or acquired thrombotic disorder.

          -  Uncontrolled or poorly-controlled hypertension.

          -  A serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to
             enrollment.

          -  Major surgery within 28 days prior to enrollment, or subcutaneous venous access device
             placement within 7 days prior to enrollment.

          -  Chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs
             (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or
             similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.

          -  Elective or planned major surgery scheduled during the course of the clinical trial.

          -  Hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months prior to
             enrollment, or with central or cavitating lesions.

          -  Radiologically documented evidence of major blood vessel invasion or encasement by
             cancer.

          -  History of GI perforation and/or fistulae within 6 months prior to enrollment, or risk
             factors for perforation.

          -  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.

          -  Pregnancy

          -  HIV-positive patients on combination antiretroviral therapy.