Clinical Trials /

Pembrolizumab And Cryoablation In Urothelial Carcinoma



This research study is examining the effectiveness of pembrolizumab plus cryoablation on people with urothelial carcinoma, including bladder cancer, that has spread.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Not yet recruiting


Phase 2

Trial Eligibility



  • Brief Title: Pembrolizumab And Cryoablation In Urothelial Carcinoma
  • Official Title: A Multicenter, Single-Arm Open Label Phase II Trial of Cryoablation in Combination With Pembrolizumab in Patients With Metastatic Urothelial Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 20-531
  • NCT ID: NCT04701918


  • Metastatic Urothelial Carcinoma
  • Bladder Cancer


PembrolizumabKeytrudaPembrolizumab + Cryoablation


This research study is examining the effectiveness of pembrolizumab plus cryoablation on people with urothelial carcinoma, including bladder cancer, that has spread.

Detailed Description

      This is an open label Phase 2, single-arm, multi-institutional clinical trial designed to
      study the combination of pembrolizumab and cryoablation on people with urothelial carcinoma,
      including bladder cancer, that has spread.

      The U.S. Food and Drug Administration (FDA) has approved both cryoablation and pembrolizumab
      as a treatment option for urothelial carcinoma, including bladder cancer, that has spread.
      However, the FDA has not yet approved the combination of the drug, pembrolizumab, and
      intervention, cryoablation, for urothelial carcinoma, including bladder cancer, that has

      Pembrolizumab is believed to work by binding to a chemical called PD-1 that is found on a
      special type of white blood cell in your body. This may help your body to be better at
      finding and destroying tumor cells. Cryoablation is an intervention which may kill cancer
      cells using extreme cold. It may help the immune system better recognize tumors and act
      against it.

      The research study procedures include screening for eligibility and study treatment,
      including evaluations and follow up visits.

      Participants will receive study treatment as long as their disease does not get worse or they
      do not have any unacceptable side effects for up to two years. Participants will be followed
      for up to 2 years after ending the study treatment.

      It is expected that about 30 people will take part in this research study.

      Biocompatibles UK Ltd, a device company under Boston Scientific, is supporting this research
      study by providing funding for the needles used in the study intervention.

Trial Arms

Pembrolizumab + CryoablationExperimentalParticipants will be given 200 mg pembrolizumab intravenously once every 3 weeks. This will continue for up to 2 years as per standard of care. Participants will receive cryoablation between the 1st and 2nd doses of pembrolizumab. Cryoablation consists of using a CT scan to guide one or more thin needles to the tumor through your skin, where extreme cold is applied.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  The subject has read, signed and dated the Informed Consent Form (ICF), having been
             advised of the risks and benefits of the trial in a language understood by the

          -  Age > 18 years at date of ICF signature having the ability to comply with the

          -  Proof of medical insurance coverage.

          -  Histologically or cytologically documented metastatic (M1, Stage IV) urothelial
             carcinoma (including renal pelvis, ureters, urinary bladder, urethra)

          -  Measurable metastatic disease with at least one site of metastatic disease > 2 cm in
             size and amenable to percutaneous image-guided cryoablation based on routine
             Interventional Radiology criteria. Metastasis sites amenable to cryoablation to
             include lymph node, peritoneum, liver, soft tissue, adrenal glands, kidney, lung, and
             bone. Must have measurable disease (by RECIST v1.1) independent of the lesion to be
             ablated (ie patient must have more than one metastasis)

          -  Life expectancy > 12 weeks.

          -  PS ECOG 0 or 1

          -  Laboratory requirements:

               -  ANC > 1 x 109/L

               -  Platelets > 75 x 109/L

               -  ALT / AST < 5 x ULN

               -  Total bilirubin <3 mg/dL

               -  INR <1.7

               -  CrCl >30 ml/min

        Exclusion Criteria:

          -  Lesion to undergo cryoablation cannot have had prior radiation therapy or other
             locoregional therapy

          -  Inability to lie flat for the cryoablation procedure.

          -  Known significant immunodeficiency due to underlying illness (e.g. HIV / AIDS) and/or
             blood CD4+ T cells <200/ul

          -  History of autoimmune disease, including but not limited to myasthenia gravis,
             myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
             inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid
             syndrome, granulomatosis with polyangiitis, Sjogren's syndrome, Guillain- Barre
             syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.

          -  Patients with a history of autoimmune-related hypothyroidism on a stable dose of
             thyroid replacement hormone are eligible for this trial.

          -  Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen
             are eligible for this trial.

          -  Patients with history of vitiligo and controlled psoriasis are eligible for the trial.

          -  Continued adverse events from a previously administered chemotherapeutic agents.

        Grade 1 adverse events and ongoing toxicities such as alopecia are exempt

          -  Treatment with systemic corticosteroids exceeding the equivalent of 10 mg/day of
             prednisone or other systemic immunosuppressive medications (including but not limited
             to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, and
             anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to Day 1, or
             anticipated requirement for systemic immunosuppressive medications during the trial

          -  Patients who receive acute, low-dose, systemic corticosteroid medications (e.g., a
             onetime dose of dexamethasone for nausea) or for prevention of hypersensitivity
             reactions to contrast agents may be enrolled in the trial.

          -  Anticoagulant or anti-platelet medication that cannot be interrupted prior to

          -  Pregnant or lactating

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicated the use of an investigational drug or that could affect the
             interpretation of the results or render the patient at high risk from treatment

          -  Prior treatment with immune checkpoint blockade therapies, including anti-CTLA-4,
             anti-PD-1, and anti-PD-L1 therapeutic antibodies

          -  Treatment with systemic immunostimulatory agents (including but not limited to IFNs,
             interleukin [IL]-2) within 6 weeks or five half- lives of the drug, whichever was
             shorter, prior to Day 1.

          -  Signs or symptoms clinically significant of infection within 2 weeks prior to Day 1.

          -  Any other systemic anti-cancer treatment (including investigational agents) within 4
             weeks prior to the first dose of study drug. Note: Participants must have recovered
             from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with
             ≤Grade 2 neuropathy may be eligible
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:up to 2 years
Safety Issue:
Description:Evaluate objective response rate of non-ablated lesion(s) for combination pembrolizumab and adjunctive cryoablation per RECIST v1.1 criteria

Secondary Outcome Measures

Measure:Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0
Time Frame:up to 2 years
Safety Issue:
Description:The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting.
Measure:Progression-Free Survival (PFS)
Time Frame:up to 2 years
Safety Issue:
Description:Defined using RECIST v1.1
Measure:Overall survival (OS)
Time Frame:up to 2 years
Safety Issue:
Description:Reported with Kaplan Meier estimates.
Measure:Duration of response (DOR)
Time Frame:up to 2 years
Safety Issue:
Description:Defined using RECIST v1.1


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Metastatic Urothelial Carcinoma
  • Bladder Cancer

Last Updated

January 8, 2021