Anti-PD(L)1 and SBRT in the Treatment of Advanced, Platinum-Refractory Urothelial Carcinoma
Condition: Urothelial Carcinoma
MeSH terms: Carcinoma; Carcinoma, Transitional Cell
Intervention: Pembrolizumab; SBRT
Intervention description: 200 mg IV q 21 days; Stereotactic body radiation therapy (SBRT) that will commence not later than the initiation of the second cycle of pembrolizumab. SBRT dose and fractionation will be at the discretion of the treating radiation oncologist, and will be selected to respect the normal tissue tolerance of adjacent organs at risk.
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a feasibility trial of anti-PDL1/PD1 (pembrolizumab) and stereotactic body radiation
      therapy (SBRT) in patients with advanced, platinum-refractory urothelial carcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must have a histologic diagnosis of urothelial carcinoma

          -  Subjects must have radiologic evidence of metastatic disease with measurable disease
             by RECIST 1.1 criteria other than the target lesion(s) for SBRT

          -  Subjects must have at least 1 metastatic lesion previously not radiated that is
             amenable to SBRT per treating radiation oncologist.

          -  Subjects must have had progression of disease within 12 months of platinum-containing
             chemotherapy (chemotherapy could have been given in the neoadjuvant, adjuvant or
             metastatic setting) for urothelial cancer

          -  ECOG performance status of 0 to 2 (Eastern Cooperative Oncology Group Performance
             Status: an attempt to quantify cancer patients' general well-being and activities of
             daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.)

          -  Absolute neutrophil count of ≥ 1000/mm3, platelet count ≥ 100,000/mm3, hemoglobin ≥
             8.0 g/dl; total bilirubin/ALT/AST < 2.5 x upper limit of normal (patients with known
             gilbert disease who have serum bilirubin ≤3x ULN may be enrolled); serum creatinine
             <3.0mg/dl or if elevated, a calculated estimated glomerular filtration rate (eGFR) of
             ≥30 mL/min/1.73 m2

          -  Subjects must have recovered to baseline or ≤ grade 1 CTCAE v 4.03 from toxicities
             related to any prior treatments unless AE(s) are clinically non-significant and/or
             stable on supportive therapy

          -  Subjects must be ≥ 2 weeks from most recent systemic therapy or most recent radiation
             therapy

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             within 28 days prior to registration.

          -  Age ≥ 18 years

        Exclusion Criteria:

          -  Prior treatment with anti-PD-1/PD-L1 and anti-CTLA-4 is NOT allowed. Prior
             intravesical BCG (Bacillus Calmette-Guerin) therapy is allowed

          -  Treatment with any investigational agent or on an interventional clinical trial within
             30 days prior to registration.

          -  No prior or concurrent malignancy is allowed except for: adequately treated basal cell
             or squamous cell skin cancer, in situ cervical cancer, localized or locally advanced
             prostate cancer definitively treated without recurrence or with biochemical recurrence
             only, or any other cancer fully treated or from which the subject has been
             disease-free for at least 2 years.

          -  Autoimmune diseases such as rheumatoid arthritis are NOT allowed. Vitiligo, mild
             psoriasis (topical therapy only) or hypothyroidism are allowed

          -  Need for systemic corticosteroids >10mg prednisone daily or equivalent alternative
             steroid

          -  Any history of organ allografts

          -  Any history of HIV or hepatitis B infection

          -  Known brain metastases