Trial of Consolidation Pembrolizumab After Concurrent Chemotherapy and Proton Reirradiation for Thoracic Recurrences of Non-Small Cell Lung Cancer
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Recurrence
Intervention: Pembrolizumab
Intervention description: Concurrent Pembrolizumab after proton reirradiation
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The main purpose of this study is to assess the safety, tolerability and anti-tumor activity
      of the experimental study drug pembrolizumab (also known as Keytruda or MK-3475) in people
      with non-small cell lung cancer (NSCLC) that has come back after radiation therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologic or cytologic diagnosis of NSCLC who have received previous intrathoracic
             radiation therapy with definitive intent and have a tumor recurrence in or near the
             prior irradiation fields. Re-biopsy of the recurrence is not required and is left to
             the discretion of the treating physician, although every effort should be made to
             confirm recurrence pathologically.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Age 18 or greater

          -  Patients with prior invasive malignancies are allowed, provided they have been treated
             with definitive intent and have no evidence of active disease requiring treatment in
             the past 2 years.

          -  Patients must be capable of giving informed consent and be willing and able to comply
             with schedule.

          -  Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) OR Direct bilirubin ≤ ULN
             for subjects with total bilirubin levels > 1.5 ULN.

          -  Platelets >100,000 cells/mm3 and ANC > 1,250 cells/mm3

          -  Creatinine ≤ 1.5 X ULN OR measured or calculated creatinine clearance ≥50 mL/min for
             subject with creatinine levels > 1.5 X institutional ULN. (GFR can also be used in
             place of creatinine or CrCl).

          -  Clinical target volume (CTV) size must be <250 cc, no more than 74 Gy of prior
             radiation in 2 Gy fractions previously administered.

        Exclusion Criteria:

          -  Allergy to Pembrolizumab or related compounds

          -  History of symptomatic CTCAEv4 grade ≥3 pneumonitis following the initial course of
             definitive radiation therapy

          -  History of symptomatic idiopathic pulmonary fibrosis or interstitial lung disease

          -  Use of continuous oxygen

          -  Diagnosis of immunodeficiency or exposure to systemic steroid therapy or any other
             form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment. (Nasal or oral inhalers are permissible).

          -  Active autoimmune disease requiring systemic treatment within the past 3 months or a
             documented history of clinically severe autoimmune disease, or a syndrome that
             requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or
             resolved childhood asthma/atopy are an exception to this rule. Subjects that require
             intermittent use of bronchodilators or local steroid injections are not excluded from
             the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's
             syndrome are not excluded from the study.

          -  History of allogenic tissue or solid organ transplant

          -  Progression while on prior therapy with an anti-programmed cell death (PD)-1,
             anti-PD-L1, anti-PD-L2, anti-tumor necrosis factor CD137, or anti-cytotoxic
             T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other
             antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)

          -  Patients with known extrathoracic metastases, including brain metastases, or known
             malignant pleural or pericardial effusion

          -  Prior radiation treatment less than 6 months from the planned start of reirradiation
             of any part of the intended treatment volume

          -  Pregnant or breast-feeding patients. Men and women of reproductive potential may not
             participate in this study unless they have agreed to use an effective contraceptive
             method while in this study.

          -  Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Known active Hepatitis B (e.g., HBsAg positive or HBV DNA detectable) or Hepatitis C
             (e.g., HCV RNA [qualitative] is detected).