Advanced Non-Small Cell Lung Cancer Progressing After at Least One Prior Therapy For Metastatic Disease
Condition: Non-small Cell Lung Cancer; Lung Cancer; Metastatic Lung Cancer; NSCLC
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis
Intervention: nivolumab and ablation
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Nivolumab releases the inhibition of the immune system against human cancers. Dramatic and
      sustained activity has been observed in advanced lung cancer. Ablation may stimulate the
      immune system by exposing new tumor antigens. Since tumors that express PD-L1 may be more
      likely to respond to nivolumab, if ablation increases PD-L1 expression (which has not been
      studied) this treatment may enhance the activity of nivolumab at both the treated site and in
      other, non-treated, tumors. Ablation is already an FDA approved treatment for cancer.
      Nivolumab was recently FDA approved for second line treatment of advanced squamous cell
      NSCLC. The goal of the study will be to determine if the combination of nivolumab and
      ablation has higher systemic activity than previously reported with nivolumab alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically or cytologically confirmed NSCLC

          -  Stage IIIB or stage IV.

          -  Patient to meet either criterion A or B:

        A) Progression after at least 1 line of systemic treatment (IV or oral) for metastatic or
        locally advanced disease. Must provide documentation systemic treatment was for either
        locally advanced or metastatic and also scan or assessment to show progression. Radiation
        does not count as 1 line.

        B) Patients progressing within 6 months of completion of neoadjuvant or adjuvant
        chemotherapy are also eligible without having treatment for metastatic disease (for example
        patient with stage I disease undergoes resection, receives systemic chemotherapy and then
        progresses to the liver (now stage IV) within 6 months of chemotherapy). Radiation does not
        count as 1 line.

          -  Ablation for advanced lung cancer is being considered by the treating physician for
             treatment or prevention of symptoms such as pain, bleeding or obstruction-
             Documentation is required in writing by MD for this criterion.

          -  At least 1 site of measurable disease that will not be treated with ablation. Sites to
             send confirmation on which lesion of measurable disease will not be ablated for
             tracking of response.

          -  At least 3 weeks since prior chemotherapy and radiation therapy

          -  No brain metastases except for patients whose metastases have been removed by surgical
             resection or have had stereotactic radiation or gamma knife with no evidence of active
             disease on MRI within 28 days of starting treatment.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

          -  Life expectancy of at least 12 weeks.

          -  Required entry laboratory parameters within 14 days of study entry: Granulocytes ≥
             1000/µl; platelet count ≥75,000/µl; absolute lymphocyte count ≥ 500/ µl; Creatinine ≤
             1.5x upper limit normal mg/dl; Bilirubin < 1.5x upper limit normal; AST ≤ 3 x upper
             limit of normal.

          -  Age > 18 years

          -  Men and women of childbearing potential enrolled in this study must agree to use
             adequate barrier birth control measures during the course of the study and up to 2
             months after.

          -  Written informed consent.

        Exclusion Criteria:

          -  Patients with a history of clinically significant chronic autoimmune disease

          -  Prior therapy with antibodies that modulate T-cell function defined as anti-CTLA-4,
             anti-PD-1, and anti-PD-L1

          -  Conditions currently requiring immunosuppressive medications

          -  Known history of HIV or hepatitis B or C

          -  Bleeding diathesis or coagulopathy that in the investigators opinion would prevent
             ablation from being safely performed.

          -  Patients with unstable angina (anginal symptoms at rest) or new-onset angina (began
             within the last 3 months) or myocardial infarction within the past 6 months.

          -  History of organ allograft even if not taking immunosuppressive medications

          -  Pregnant or breast-feeding.