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
spread.
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.
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
subject.
- Age > 18 years at date of ICF signature having the ability to comply with the
protocol.
- 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
cryoablation
- 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
complications.
- 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
