Testing the Addition of Radiation Therapy to Immunotherapy for Merkel Cell Carcinoma
Condition: Advanced Merkel Cell Carcinoma; Clinical Stage III Merkel Cell Carcinoma AJCC v8; Clinical Stage IV Merkel Cell Carcinoma AJCC v8; Metastatic Merkel Cell Carcinoma; Pathologic Stage III Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8; Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8; Pathologic Stage IV Merkel Cell Carcinoma AJCC v8
MeSH terms: Carcinoma, Merkel Cell; Carcinoma
Intervention: Pembrolizumab; Stereotactic Body Radiation Therapy
Intervention description: Given IV; Undergo SBRT
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well pembrolizumab with or without stereotactic
      body radiation therapy works in treating patients with Merkel cell cancer that has spread to
      other places in the body (advanced). Immunotherapy with monoclonal antibodies, such as
      pembrolizumab, may help the body's immune system attack the cancer, and may interfere with
      the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses
      special equipment to position a patient and deliver radiation to tumors with high precision.
      This method can kill tumor cells with fewer doses over a shorter period and cause less damage
      to normal tissue. Giving pembrolizumab with stereotactic body radiation therapy may work
      better in treating patients with Merkel cell cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have pathologically (histologically or cytologically) proven diagnosis
             of MCC by local pathology review

          -  Have measurable disease based on RECIST 1.1 including at least two cancerous deposits;
             at least one deposit must be RECIST measurable while at least one deposit must meet
             criteria for SBRT; non-radiated tumor will be identified prior to randomization on the
             protocol

          -  Patients must have advanced or metastatic MCC defined as evidence of distant
             metastasis(es) on imaging

               -  Patients with locoregionally confined disease are not eligible

          -  No prior immunotherapy for advanced/metastatic MCC

          -  Patients with known or suspected central nervous system (CNS) metastases, untreated
             CNS metastases, or with the CNS as the only site of disease are excluded; however,
             subjects with controlled brain metastases will be allowed to enroll; controlled brain
             metastases are defined as no radiographic progression for at least 4 weeks following
             radiation and/or surgical treatment (or 4 weeks of observation if no intervention is
             clinically indicated), and off of steroids for at least 2 weeks, and no new or
             progressive neurological signs and symptoms

          -  Patients having received palliative radiotherapy for extracranial metastasis(es) are
             eligible as long as there are 2 cancerous deposits that have not received prior
             radiation therapy (RT) and they meet the following criteria

               -  No prior radiation therapy (> 5 Gy) to the metastasis intended to be treated with
                  SBRT

          -  No history of the following:

               -  Autoimmunity requiring systemic immunosuppression within 2 years

               -  Patients known to be human immunodeficiency virus (HIV) positive are eligible if
                  they meet the following:

                    -  CD4 counts >= 350 mm^3

                    -  Serum HIV viral load of < 25,000 IU/ml

          -  No other active malignancy that the investigator determines would interfere with the
             treatment and safety analysis

          -  Not pregnant and not nursing, because this study involves an investigational agent
             whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
             are unknown; therefore, for women of childbearing potential only, a negative (if your
             test schedule specifically indicates a urine or serum pregnancy test, add that
             information at this point) pregnancy test done =< 28 days prior to registration is
             required

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin >= 9.0 g/dl

          -  Total bilirubin =< 2.0 mg/dl

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limit
             of normal (ULN)

          -  Systolic blood pressure (BP) =< 150 mg HG

          -  Diastolic BP =< 90 mg HG

          -  Albumin > 3 mg/dl

          -  Blood urea nitrogen (BUN) =< 30 mg/dl

          -  Creatinine =< 1.7 mg/dl

          -  The following imaging workup to document metastases within 45 days prior to study
             registration are required: CT scans of the chest, abdomen and pelvis with radionuclide
             bone scan OR whole body (at least skull base to midthigh) positron emission tomography
             (PET)/CT