Study of Combined Ionizing Radiation and Ipilimumab in Metastatic Non-small Cell Lung Cancer (NSCLC)
Condition: Non-small Cell Lung Cancer (NSCLC)
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to investigate how effective and how safe the combination of
      radiation therapy and an investigational medication targeting the immune system known as
      Ipilimumab in the treatment of metastatic non-small cell lung cancer (NSCLC).

      The investigators would like to see if this combination of radiation and Ipilimumab can
      stimulate the body's immune system to stop the growth of tumors that are outside the field of
      radiation. The investigators would like see if using this combination of radiation therapy
      with Ipilimumab could help the body reject the patient's own tumor or at least help their
      immune system to maintain the disease stable and/or slow its growth.

      Radiation therapy (RT) is currently a standard procedure for treatment of NSCLC. Ipilimumab
      is considered an investigational medication because it is not approved by the Food and Drug
      Administration (FDA) for the treatment of NSCLC. Ipilimumab has been approved by the FDA for
      the treatment of metastatic melanoma.
    

Detailed description: 
      Research Hypothesis:

        1. Through a combination of local RT and ipilimumab an anti-tumor immune response is
           elicited at the irradiated site, as an in vivo, individualized immunization that is
           systemically effective, as reflected by objective responses outside the RT field
           (abscopal effect).

        2. The immune response can be prospectively monitored among the treated patients.

      Objective 1: Evaluate the safety and therapeutic efficacy of anti-cytotoxic
      T-lymphocyte-associated protein -4 mono clonal Antibody (anti-CTLA-4 mAb) and concurrent
      local RT in NSCLC patients with metastatic disease.

      An open label phase II trial will evaluate the preliminary efficacy of the combination of Ipi
      and RT, applied to a single metastatic site. Efficacy is measured with respect to systemic
      tumor responses (abscopal response, outside the field of therapy) defined by immune-related
      Response Criteria (irRC) in all non-irradiated measurable lesions, as a demonstration of an
      effective anti-tumor immune response. Secondary endpoints include local response in the RT
      treated tumor, progression free survival, and overall survival.

      Objective 2: Determine the effects of RT and anti-CTLA-4 mAb on development of anti-tumor
      immunity.

      The investigators hypothesize that RT will convert the irradiated tumor into an in situ
      vaccine and elicit an endogenous tumor-specific cellular and humoral immune response, which
      in the presence of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade will promote
      immune-mediated destruction of the irradiated and abscopal metastases. Pre- and
      post-treatment tumor biopsies will be examined for changes in immune contexture, and blood
      for evidence of emerging anti-tumor immune responses. Associations with clinical response
      will be explored.
    

Intervention name(s): Ipilimumab; Radiotherapy (IMRT or 3-D CRT)
Intervention type(s): Drug; Radiation
Other intervention name(s): Yervoy
Intervention MeSH terms: Ipilimumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: lung cancer; NSCLC; lung; cancer; radiation; immunotherapy; metastatic