A Phase II Randomized Trial of Immunotherapy Plus Radiotherapy in Metastatic Genitourinary Cancers
Condition: Metastatic Renal Cell Carcinoma; Metastatic Urothelial Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Nivolumab; Atezolizumab; Radiation & immunotherapy; Pembrolizumab
Intervention description: Nivolumab will be given to patients with renal cell carcinoma on days 1,15, 29, 43 and 57.; Atezolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.; Radiation is given to one lesion, 30 Gray (Gy) in 3 fractions of 10 Gy each. over a one week interval (with a minimum of 36hrs between each fraction). On the day of radiation (Day 1) immunotherapy is administered and repeated on the scheduled days. Patients will receive radiation on Day 1 and immunotherapy will be given ± 24hr from Day 1.; Pembrolizumab will be given to patients with urothelial carcinoma on days 1,22,43,64.
Intervention MeSH terms: Pembrolizumab; Nivolumab; Atezolizumab; Immunomodulating Agents; Immunologic Factors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 19 Years
Maximum age: 90 Years
Healthy volunteers: No

Summary:

      The trial is open to patients who have metastatic renal cell carcinoma/urothelial (bladder)
      carcinoma with at least 2 measurable sites of disease. All eligible patients will be randomly
      assigned to immunotherapy(nivolumab/atezolizumab/pembrolizumab) versus immunotherapy
      (nivolumab/atezolizumab/pembrolizumab) plus radiotherapy, 10 Gy x3 (conformally or by
      intensity modulation radiation therapy/Image-guided radiation therapy (IMRT/IGRT) to
      maximally spare normal tissue), to one of their measurable lesions.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Ability to understand and the willingness to sign a written informed consent document;

          2. Any prior therapy is permitted except prior therapy with PD1/PDL1 inhibitor.

          3. Histologic diagnosis of metastatic renal cell carcinoma or urothelial cancer;

          4. Patients must have at least 2 distinct measurable metastatic sites at least 1 cm or
             larger in their largest diameter per RECIST 1.1

          5. Patients must have adequate organ and marrow function as defined by initial laboratory
             tests.

          6. At least 2 weeks since last chemotherapy and 4 weeks since last immunotherapy
             treatment.

          7. Performance status Eastern cooperative oncology group (ECOG) 0-1

          8. Men and women, ages > 18 years of age.

          9. Life expectancy > 3 months

         10. Stable brain metastases for at least 4 weeks and not steroid dependent

         11. Women of childbearing potential (WOCBP) must be using an adequate method of
             contraception to avoid pregnancy throughout the study and for up to 8 weeks after the
             study in such a manner that the risk of pregnancy is minimized. Should a woman become
             pregnant or suspect she is pregnant while she is enrolled in this study, she should
             inform her treating physician immediately.

        Exclusion Criteria:

          1. Patients having no lesions outside the field of radiation thus nullifying the ability
             to measure an abscopal effect;

          2. Any other malignancy from which the patient has been disease-free for less than 5
             years, with the exception of adequately treated and cured basal or squamous cell skin
             cancer, superficial bladder cancer or carcinoma in situ of the cervix;

          3. Autoimmune/auto inflammatory disease: Patients with a history of inflammatory bowel
             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 [e.g., Wegener's Granulomatosis];

          4. Any underlying medical or psychiatric condition, which in the opinion of the
             Investigator, will make the administration of study drug hazardous or obscure the
             interpretation of adverse events (AEs), such as a condition associated with frequent
             diarrhea;

          5. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to
             one month prior to or after any dose of PD-1/PDL-1 blocking antibody).

          6. A history of prior treatment with PD-1/PDL-1blocking antibody;

          7. Patients who have had immunotherapy within 4 weeks prior to entering the study.

          8. Concomitant therapy with any of the following: interleukin -2 (IL-2), interferon or
             other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive
             agents; other investigation therapies; or chronic use of systemic corticosteroids;

          9. Patients undergoing therapy with other investigational agents or other chemotherapy
             agents;

         10. Women who:

               1. are unwilling or unable to use an acceptable method to avoid pregnancy for the
                  entire study period and for at least 8 weeks after cessation of study drug, or

               2. have a positive pregnancy test at baseline, or

               3. are pregnant or breastfeeding

         11. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
             treatment of either a psychiatric or physical (e.g., infectious) illness