Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma
Condition: Merkel Cell Carcinoma; Skin Cancer
MeSH terms: Carcinoma, Merkel Cell; Carcinoma; Skin Neoplasms
Intervention: Nivolumab; Ipilimumab; Stereotactic Body Radiation Therapy (SBRT)
Intervention description: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks.; Ipilimumab 1 mg/kg/dose IV q6 weeks.; Stereotactic Body Radiation Therapy 24Gy in 3 fractions.
Intervention MeSH terms: Nivolumab; Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants are randomly assigned in a 1:1 ratio to Arm A (nivolumab + ipilimumab), or Arm B (nivolumab + ipilimumab + SBRT).
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Merkel cell carcinoma (MCC); Metastatic; Metastasis; Stereotactic body radiation therapy (SBRT); Immunology; Antibody; Nivolumab; Ipilimumab; Metastatic skin cancer; Cutaneous

Summary:

      The purpose of this study is to test the effectiveness, safety, and tolerability of the drugs
      nivolumab plus ipilimumab with or without the addition of stereotactic body radiation therapy
      (SBRT). Nivolumab is an antibody (a type of human protein) that is being tested to see if it
      will stimulate the body's immune system to work against tumor cells. This study will test an
      investigational use of nivolumab.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least 18 years of age

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status less than 2

          -  Active disease measurable by CT, MRI or clinical exam.

          -  Prior chemotherapy or immunotherapy will be allowed if new or persistent measurable
             site(s) of disease are present.

          -  Prior radiation therapy will be allowed if there is active measurable disease burden.

          -  Must be either recurrent, unresectable or Stage IV American Joint Committee on Cancer
             (AJCC) (7th edition) and have histologically confirmed Merkel cell carcinoma with at
             least 2 distinct lesions in order to be eligible.

          -  Must have at least 2 distinct lesions as documented by a complete physical examination
             or imaging studies within 4 weeks prior to randomization. Imaging studies must include
             a diagnostic CT scan of the involved disease sites and all known sites of resected
             disease and brain magnetic resonance (MRI) or CT (brain CT allowable if MRI is
             contraindicated or if there is no known history of resected brain lesions).

          -  Tumor tissue from the core biopsy or resected site of disease must be provided for
             biomarker analyses.

        Exclusion Criteria:

          -  History of Grade 3 toxicity or use of infliximab with prior immunotherapy

          -  Patients with active brain metastasis.

          -  Active, known, or suspected autoimmune disease. Potential participants with type I
             diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only
             requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or
             alopecia) not requiring systemic treatment are permitted to enroll.

          -  Patients with prior history of non-Merkel cell carcinoma malignancies are excluded
             except adequately treated basal cell, squamous cell skin cancer, chronic lymphocytic
             leukemia or other indolent diseases not requiring therapy; adequately treated, with
             curative intent, cancer from which the patient is currently in complete remission per
             investigator's judgment; or patients with history of breast cancer and no evidence of
             disease on hormonal therapy to prevent recurrence and patients with prostate cancer on
             adjuvant hormonal therapy with undetectable PSA are eligible.

          -  A condition requiring systemic treatment with either corticosteroids (> 10 mg daily
             prednisone equivalent) or other immunosuppressive medications within 14 days of
             randomization. Inhaled or topical steroids are permitted in the absence of active
             autoimmune disease.