What side effects are associated with this type of intervention?

Common treatments for bladder cancer, such as PD-1 inhibitors (e.g., pembrolizumab) and PD-L1 inhibitors (e.g., avelumab), often have side effects including fatigue, rash, diarrhea, and immune-related adverse events like pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Cryoablation, a procedure that uses extreme cold to destroy cancer cells, can cause side effects such as pain, swelling, bleeding, and infection at the treatment site. Combining these therapies may increase the risk of these side effects, and patients should be closely monitored.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been approved by the FDA for the treatment of bladder cancer, specifically for patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy or have disease progression during or following platinum-containing chemotherapy. Avelumab, a PD-L1 inhibitor, has also received FDA approval for the treatment of locally advanced or metastatic urothelial carcinoma that has progressed during or following platinum-based chemotherapy. These approvals are based on their ability to target the PD-1/PD-L1 pathway, which is crucial in the immune response against cancer cells. The combination of these immunotherapies with cryoablation is currently being studied to potentially enhance their efficacy.

What other types of research exist?

Promising novel alternatives for bladder cancer treatment in 2024 include Enfortumab Vedotin, which has shown efficacy in patients previously treated with platinum and PD-1/PD-L1 inhibitors, and Sacituzumab Govitecan, which is being studied in patients progressing after platinum-based chemotherapy and checkpoint inhibitors. Additionally, combination therapies involving Cabozantinib and Nivolumab, as well as experimental approaches like CAR-T cell therapies, are also emerging as potential options.

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Checkpoint Inhibitor

Pembrolizumab + Cryoablation for Bladder Cancer

Phase 2

Recruiting

Led By Eric Wehrenberg-Klee, MD

Research Sponsored by Massachusetts General Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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)

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

Must not have

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

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two treatment combinations for advanced bladder cancer. It targets patients whose cancer has spread. The drugs help the immune system attack cancer cells, and the freezing procedure kills cancer cells directly.

Who is the study for?

Adults over 18 with metastatic urothelial carcinoma, including bladder cancer, who have measurable disease and are in good enough health for the treatment. They must not have had certain autoimmune diseases or recent immunosuppressive treatments, no prior immune checkpoint therapies, and should be able to lie flat for cryoablation.

What is being tested?

The trial is testing the combination of pembrolizumab (an immunotherapy drug) with cryoablation (a procedure that freezes cancer cells) on patients whose bladder cancer has spread to see if it's effective.

What are the potential side effects?

Pembrolizumab may cause immune system-related side effects like inflammation in organs, skin reactions, hormone gland problems (like thyroid), and infusion reactions. Cryoablation can cause pain at the site of treatment, bleeding, infection risk increase.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a tumor larger than 2 cm that can be treated with cryoablation, and I have more than one metastasis.

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My cancer, found in parts of my urinary system, has spread to other areas.

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I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I cannot stop my blood thinner medication before undergoing a freezing procedure.

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I have not had significant infection symptoms in the last 2 weeks.

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I haven't taken any immune-boosting drugs in the last 6 weeks.

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I haven't taken high doses of steroids or immunosuppressants recently.

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I have a history of autoimmune disease.

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I have previously been treated with immune therapy drugs.

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I cannot lie flat for a medical procedure.

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My lesion for cryoablation has not received prior radiation or local treatments.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective Response Rate

Secondary study objectives

Duration of response (DOR)

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

Overall survival (OS)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Pembrolizumab/Avelumab + CryoablationExperimental Treatment3 Interventions

If 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

Avelumab

2017

Completed Phase 2

~2440

Cryoablation

2017

Completed Phase 2

~1030

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Pembrolizumab and Avelumab are immunotherapy drugs that target the PD-1 and PD-L1 pathways, respectively. These pathways are involved in the immune system's ability to recognize and attack cancer cells. By inhibiting PD-1 or PD-L1, these drugs enhance the immune response against cancer cells, making it easier for the body to fight the tumor. Cryoablation, on the other hand, is a localized treatment that involves freezing cancer cells to kill them directly. Combining these therapies can be particularly effective for bladder cancer patients because cryoablation can reduce tumor burden locally, while immunotherapy can help the immune system target any remaining cancer cells throughout the body. This dual approach can potentially improve treatment outcomes by addressing both local and systemic disease.

[Immunological biomarker research in uro-oncology-using the example of urothelial cancer].