SBRT (Stereotactic Body Radiation Therapy) in Combination With Nivolumab/Ipilimumab in Renal Cell Carcinoma (RCC) / Kidney Cancer Patients
Condition: Kidney Cancer Metastatic; Kidney Cancer; Kidney Cancer, Stage IV
MeSH terms: Kidney Neoplasms; Carcinoma, Renal Cell
Intervention: Nivolumab/Ipilimumab; SBRT
Intervention description: IV immunotherapy; SBRT will be delivered in conjunction with immunotherapy
Intervention MeSH terms: Nivolumab; Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Healthy volunteers: No

Summary:

      This is a multi-institution, single-arm phase II study to determine the safety and efficacy
      of SBRT (up to 2 metastatic sites preferentially lung, mediastinum or bone in combination of
      nivolumab and ipilimumab in patients with metastatic renal cell carcinoma(with a clear-cell
      component and at least 1 measurable metastatic lesion that is not being irradiated).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological confirmation of RCC with a clear-cell component

          -  Metastatic (AJCC Stage IV) RCC

          -  Prior adjuvant or neoadjuvant therapy for localized or locally advanced RCC is allowed
             provided recurrence occurred = or > 6 months after the last dose of the adjuvant or
             neoadjuvant therapy

          -  Any number of prior systemic treatment regimen in the advanced/metastatic setting is
             allowed (cytokine, anti-angiogenic, mammalian target of rapamycin (mTOR) inhibitor or
             clinical trial) including previously untreated patients

          -  Karnofsky Performance Status (KPS) of at least 70%

          -  Life expectancy of at least 3 months

          -  At least 2 metastatic sites of which at least 1 must be measurable as per RECIST 1.1

          -  Archival Formalin-fixed paraffin-embedded (FFPE) tumor tissue must be available for
             correlative studies (Note: Fine Needle Aspiration (FNA) and bone metastases samples
             are not acceptable for submission)

          -  Patients with favorable, intermediate and poor risk categories will be eligible for
             the study. Patients must be categorized according to favorable versus
             intermediate/poor risk status at registration. International Metastatic RCC Database
             Consortium (IMDC) must be used to determine prognostic factors

        Exclusion Criteria:

          -  Subjects with previously treated brain or CNS (Central nervous system) metastases are
             eligible provided that the subject has recovered from any acute effects of
             radiotherapy and is not requiring steroids, and any whole brain radiation therapy was
             completed at least 4 weeks prior to study drug administration, or any stereotactic
             radiosurgery was completed at least 2 weeks prior to study drug administration. Liver
             metastases will not be included as part of the radiated lesions to be treated.

        Medical History and Concurrent Diseases:

          -  Prior treatment with an anti-Programmed cell death(PD) -1, anti-PD-L1, anti-PD-L2,
             anti-CD137(cluster of differentiation), or anti-CTLA-4 (cytotoxic
             T-lymphocyte-associated protein ) antibody, or any other antibody or drug specifically
             targeting T-cell co-stimulation or checkpoint pathways. Prior treatment with high dose
             interleukin (HD IL)-2 is allowed.

          -  Any active or recent history of a known or suspected autoimmune disease or recent
             history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone
             equivalent) or immunosuppressive medications except for syndromes which would not be
             expected to recur in the absence of an external trigger. Subjects with vitiligo or
             type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only
             requiring hormone replacement are permitted to enroll. Patients with psoriasis not
             requiring active, systemic treatment are allowed.

          -  Any condition requiring systemic treatment with corticosteroids (> 10 mg daily
             prednisone equivalents) or other immunosuppressive medications within 14 days prior to
             first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to
             10 mg daily prednisone equivalents are permitted in the absence of active autoimmune
             disease

          -  Uncontrolled adrenal insufficiency

          -  Requirement for anti-coagulation with Coumadin, low molecular weight heparin and
             anti-thrombin inhibitors will be accepted if anticoagulation has been stable for at
             least 4 weeks and no recent history of prior bleeding complications.

          -  Prior malignancy active within the previous 3 years except for locally curable cancers
             that have been apparently cured such as basal or squamous cell skin cancer,
             superficial bladder cancer, or carcinoma in situ of the cervix, breast or low risk
             Gleason 6 prostate cancer

          -  Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS)

          -  Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic
             infection

          -  Known medical condition (eg, a condition associated with diarrhea or acute
             diverticulitis) that, in the investigator's opinion, would increase the risk
             associated with study participation or study drug administration or interfere with the
             interpretation of safety results

          -  Major surgery (eg, nephrectomy) less than 28 days prior to the first dose of study
             drug

          -  Anti-cancer therapy less than 14 days prior to the first dose of study drug or
             palliative, focal radiation therapy less than 14 days prior to the first dose of study
             drug

          -  Presence of any toxicities attributed to prior anti-cancer therapy, other than
             alopecia, that have not resolved to Grade 1 (NCI CTCAE v4) or baseline before
             administration of study drug

        Physical and Laboratory Test Findings:

          -  Any of the following laboratory test findings:

               -  White blood cell (WBC) < 2,000/mm3

               -  Neutrophils < 1,500/mm3

               -  Platelets < 100,000/mm3

               -  aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x ULN (> 5
                  x ULN if liver metastases are present)

               -  Total Bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome, who can have
                  total bilirubin < 3.0 mg/dL)

               -  Serum creatinine > 1.5 x upper limit of normal (ULN) or creatinine clearance < 40
                  mL/min (measured or calculated by Cockroft-Gault formula)

        Allergies and Adverse Drug Reaction:

          -  History of severe hypersensitivity reaction to any monoclonal antibody or study drug
             components

        Other Exclusion Criteria:

          -  Prisoners or subject who are involuntarily incarcerated

          -  Not suitable for SBRT treatment

          -  Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical illness