Evaluation of Circulating T Cells and Tumor Infiltrating Lymphocytes (TILs) During / After Pre-Surgery Chemotherapy in Non-Small Cell Lung Cancer (NSCLC)
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Ipilimumab; Paclitaxel, Cisplatin, Carboplatin
Intervention description: Neoadjuvant (Pre-Surgery): Cycles 2 and 3: Ipilimumab 10 mg/kg IV over 90 minutes
Adjuvant (Post-Surgery): Ipilimumab 10 mg/kg IV every 3 weeks times 2 doses beginning 4 weeks postoperative ( up to 10 weeks if needed for recovery)
Maintenance: Ipilimumab 10 mg/kg/IV every 12 weeks times 2 doses; Neoadjuvant (Pre-Surgery) Cycle 1: Paclitaxel 175 mg/m2 IV over 3 hours , followed by Cisplatin 75 mg/m2 IV over 60 minutes or carboplatin AUC 6 IV over 30-60 minutes on day 1(Every 21 days x 1 cycle)
Cycles 2 and 3: Ipilimumab 10 mg/kg IV over 90 minutes, Paclitaxel 175 mg/m2 IV over 3 hours , followed by Cisplatin 75 mg/m2 IV over 60 minutes or carboplatin AUC 6 IV over 30-60 minutes on day 1(Every 21 days x 2 cycles)
Intervention MeSH terms: Paclitaxel; Carboplatin; Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non Small Cell Lung Cancer; Lung Cancer; Non Small Cell

Summary:

      The purpose of this study is to evaluate whether the combination of neoadjuvant chemotherapy
      (chemotherapy before surgery) plus ipilimumab for lung cancer increases the number of
      patients with detectable circulating T cells with specificities against tumor associated
      antigens (TAA) from zero percent (0%) of patients prior to therapy to 20% of patients after
      neoadjuvant chemotherapy plus ipilimumab.

      This is an open label Phase 2 trial. Patients with clinical stage 1B (>4 cm), 2, (N0-2) or 3
      non-small cell lung cancer (NSCLC) and no prior therapy for the current diagnosis of lung
      cancer will be eligible for the study. Subjects will receive 3 cycles of neoadjuvant
      chemotherapy (paclitaxel + cisplatin/carboplatin). Ipilimumab will be administered during
      Cycles 2 and 3 of standard chemotherapy and for up to 4 cycles alone after surgery. Subjects
      will undergo standard clinically indicated surgical resection of their lung cancer as deemed
      appropriate by their surgeon.

      Standard diagnostic and staging work up will be performed including: pathologic/histologic
      diagnosis of NSCLC, Positron Emission Tomography (PET)/Computed Tomography (CT) scan, brain
      imaging, and mediastinoscopy. Three cycles of neoadjuvant chemotherapy will be given.
      Ipilimumab will be added to neoadjuvant chemotherapy for cycles 2 and 3. Standard surgical
      evaluation and therapy will be performed following completion of neoadjuvant therapy. Two
      cycles of single agent ipilimumab will be given after surgery (adjuvantly), followed by 2
      cycles of maintenance therapy.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients are eligible to be in the study if they meet all of the following criteria:

          -  Histologically or cytologically documented non-small cell lung cancer (NSCLC)

          -  Clinical stage 1B (≥4cm per CT), Stage 2A/2B, or Stage 3 (N0-2) amenable to surgical
             resection

          -  Patients must be deemed a surgical candidate

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  No prior chemotherapy for current diagnosis of lung cancer

          -  Age is ≥ (greater than or equal to) 18 years

          -  No active invasive malignancy in the past 2 years other than non-melanoma skin cancer.
             Cancers that are in-situ are not considered invasive

          -  Signed written informed consent including Health Insurance Portability and
             Accountability Act (HIPAA) authorization according to institutional guidelines

          -  Adequate Organ Function:

               -  Absolute neutrophil count (ANC) or absolute granulocyte count (AGC) ≥1500 per
                  microliter (uL)

               -  Platelets ≥ 100,000 per uL

               -  Total bilirubin ≤(less than or equal to)1.5 milligram per deciliter (mg/dL)

               -  Creatinine clearance ≥ 45 milliliter per minute (mL / min); (Creatinine < 2mg /
                  dL to receive cisplatin)

               -  Serum glutamic-oxaloacetic transaminase / Serum glutamic pyruvic transaminase
                  (SGOT/SGPT) ≤ 2.5x institutional upper limit normal (ULN)

          -  Females of child-bearing potential (not surgically sterilized and between menarche and
             1 year post menopause) must test negative for pregnancy within 48 hours prior to any
             initial study procedure based on a serum pregnancy test. Both sexually active males
             and females of reproductive potential must agree to use a reliable method of birth
             control, as determined by the patient and their health care team, during the study and
             for 3 months following the last dose of study drug. If subject uses appropriate
             contraceptive methods (the use of two forms at the same time) from the time of the
             initial serum pregnancy test, then the subsequent pregnancy test can be done within 72
             hours of receiving study drug administration. If appropriate contraceptive measures
             are not begun immediately with the first serum pregnancy test, then subsequent serum
             pregnancy tests must be done within 48 hours prior to the study drug administration

          -  Patients must agree to research blood sampling to participate in study

        Exclusion Criteria:

        Patients will be excluded from the study if they meet any of the following criteria:

          -  Have had treatment within the last 30 days with a drug that has not received
             regulatory (Food and Drug Administration (FDA)) approval for any indication at the
             time of study entry

          -  Concurrent administration of any other anti-tumor therapy

          -  Inability to comply with protocol or study procedures

          -  Active infection requiring intravenous (IV) antibiotics, antifungal or antiviral
             agents, that in the opinion of the investigator would compromise the patient's ability
             to tolerate therapy

          -  Major surgery (other than definitive lung cancer surgery) within two weeks of study or
             other serious concomitant systemic disorders that, in the opinion of the investigator,
             would compromise the safety of the patient or compromise the patient's ability to
             complete the study

          -  Myocardial infarction (MI) having occurred less than 6 months before inclusion, any
             known uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia, or
             cardiac failure not controlled by medications

          -  Contraindication to corticosteroids

          -  Unwillingness to stop taking herbal supplements while on study

          -  Female patients who are pregnant or breast-feeding

          -  Autoimmune disease. Patients with a history of inflammatory bowel disease, including
             ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients
             with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic
             progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
             vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune
             origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis)

          -  Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to
             1 month before or after any dose of ipilimumab)

          -  A history of prior treatment with ipilimumab or prior CD137 agonist or cytotoxic
             T-lymphocyte-associated protein (CTLA 4) inhibitor or agonist

          -  Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for
             treatment of either a psychiatric or physical (e.g., infectious) illness