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Metastatic Urothelial CarcinomaPhase 2NCT04701918

Cryoablation With Pembrolizumab Or Avelumab In Urothelial Carcinoma

A Phase 2 study testing Pembrolizumab, Cryoablation and Avelumab in people with Metastatic Urothelial Carcinoma and Bladder Cancer, run by Massachusetts General Hospital at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab, Cryoablation and Avelumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
2 sitesUnited States
Study dates
4 Jun 2021to 1 Dec 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Multicenter, Single-Arm Open Label Phase II Trial of Cryoablation in Combination With Pembrolizumab or Avelumab in Patients With Metastatic Urothelial Carcinoma

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

Read the detailed description

This is an open label Phase 2, single-arm, multi-institutional clinical trial designed to study the combination of pembrolizumab and cryoablation or avelumab 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, pembrolizumab, and avelumab as treatment options for urothelial carcinoma, including bladder cancer, that has spread. However, the FDA has not yet approved the combination of the drugs, pembrolizumab or avelumab, 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. Avelumab is believed to work by binding a similar molecule called PD-L1. 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.

Being tested
Pembrolizumab, Cryoablation, Avelumab
Keywords
Metastatic Urothelial Carcinoma, Bladder Cancer
Medical subject headings
Carcinoma, Transitional Cell, Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called Keytruda

    Intravenous injection through a vein (IV) every 3 weeks

  • CryoablationProcedure or surgery

    Needle inserted through the skin and into the tumor using CT guidance

  • AvelumabDrug

    Also called Bavencio

    Intravenous injection through a vein (IV) every 2 weeks

Study groups in NCT04701918
Study groupRoleWhat they receive
Pembrolizumab/Avelumab + CryoablationExperimentalIf patient is receiving pembrolizumab: Participants 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. If patient is receiving avelumab: Participants will be given 800 mg avelumab intravenously once every 2 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 avelumab. 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.
Receives: Drug: Pembrolizumab; Procedure: Cryoablation; Drug: Avelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate

    Evaluate objective response rate of non-ablated lesion(s) for combination pembrolizumab/avelumab and adjunctive cryoablation per RECIST v1.1 criteria

    Measured: up to 2 years

Secondary outcomes (4)

  1. Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0

    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.

    Measured: up to 2 years

  2. Progression-Free Survival (PFS)

    Defined using RECIST v1.1

    Measured: up to 2 years

  3. Overall survival (OS)

    Reported with Kaplan Meier estimates.

    Measured: up to 2 years

  4. Duration of response (DOR)

    Defined using RECIST v1.1

    Measured: up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jan 2021
  2. Study start4 Jun 2021
  3. Primary completion1 Dec 2025
  4. Study completion1 Dec 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04701918
Sponsor's protocol ID
20-531
Status last verified
Jan 2026
First submitted
14 Dec 2020
Last updated
22 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab, Cryoablation and Avelumab in people with Metastatic Urothelial Carcinoma and Bladder Cancer, run by Massachusetts General Hospital at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (time frame: up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04701918.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2026.

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