Pembrolizumab + Cryoablation for Bladder Cancer

Recruiting at 1 trial location

Overseen By Eric Wehrenberg-Klee, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Corticosteroids, Anticoagulants

Disqualifiers: Autoimmune diseases, Immunodeficiency, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: up to 2 years

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of pembrolizumab (KEYTRUDA) and avelumab combined with cryoablation against advanced bladder cancer that has spread. Cryoablation uses extreme cold to target and destroy cancer cells. Participants will receive one of these medications through an IV, along with cryoablation, to determine if this combination can better manage the cancer. The trial seeks individuals with bladder cancer that has metastasized and have at least one sizable tumor treatable with cryoablation. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take certain medications like high-dose corticosteroids or anticoagulants that can't be paused before the procedure. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pembrolizumab, also known as Keytruda, is generally safe and has treated various types of cancer. Some people might experience side effects like fatigue, rash, or nausea.

Studies have found that cryoablation, which uses extreme cold to target tumors, is safe for bladder tumors and helps reduce the risk of cancer returning or worsening. When combined with pembrolizumab, it remains well-tolerated by patients.

For avelumab, evidence suggests it is also safely used in cancer treatments, though it may cause side effects like fatigue or infusion-related reactions.

Overall, both pembrolizumab and avelumab, when combined with cryoablation, have shown good tolerance. However, as with any treatment, some side effects may occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the use of pembrolizumab combined with cryoablation for bladder cancer because it offers a novel approach that enhances the body's immune response while directly targeting the tumor. Unlike traditional treatments like chemotherapy, pembrolizumab is an immunotherapy that boosts the immune system to attack cancer cells. The addition of cryoablation, a technique that uses extreme cold to destroy tumors, helps to further shrink the cancer and may enhance the immune response triggered by pembrolizumab. This combination could potentially improve outcomes by targeting the cancer from multiple angles.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that pembrolizumab, a treatment that aids the immune system, is effective against bladder cancer. It targets a protein called PD-1, enabling the immune system to attack cancer cells. Studies have found that pembrolizumab can reduce the risk of cancer recurrence or death by 31% compared to disease monitoring alone. In this trial, some participants will receive pembrolizumab combined with cryoablation, a procedure that freezes and destroys cancer cells, to evaluate if the treatment might be more effective. Previous patients treated with pembrolizumab experienced significant benefits, and it has been shown to be safe. This combination is being studied to determine if it can better manage urothelial carcinoma. ^{1 5 6 7 8}

Who Is on the Research Team?

Eric Wehrenberg-Klee, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Your blood cell counts, liver function, and kidney function must be within certain limits.

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

I am over 18 and can follow the study's requirements.

Exclusion Criteria

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

You can participate in the trial if you have vitiligo or psoriasis that is under control.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab or avelumab in combination with cryoablation. Pembrolizumab is administered every 3 weeks and avelumab every 2 weeks, with cryoablation occurring between the 1st and 2nd doses.

up to 2 years

Bi-weekly or tri-weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits for up to 2 years.

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cryoablation
• Pembrolizumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Pembrolizumab/Avelumab + Cryoablation Experimental Treatment 3 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.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Biocompatibles UK Ltd

Industry Sponsor

Trials

25

Recruited

3,300+

Published Research Related to This Trial

In the Phase III KEYNOTE-045 trial, pembrolizumab significantly improved overall survival in patients with second-line metastatic urothelial carcinoma compared to standard treatments like docetaxel, paclitaxel, and vinflunine.

Early results from the Phase II KEYNOTE-052 trial suggest that pembrolizumab is effective for first-line treatment in patients with metastatic urothelial carcinoma who are not eligible for cisplatin, leading to its FDA approval for these indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of advanced urothelial cancer. Lundgren, KT., Farina, MS., Bellmunt, J.[2018]

In a study comparing 121 patients treated with pembrolizumab to 67 patients receiving conventional chemotherapy for advanced urothelial carcinoma, pembrolizumab showed a significant improvement in overall survival with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death compared to chemotherapy.

Despite the older age and poorer health status of patients receiving pembrolizumab, the treatment demonstrated a clinical benefit over traditional chemotherapy, suggesting its effectiveness as a second-line therapy in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of pembrolizumab with conventional chemotherapy after first-line platinum-based chemotherapy for advanced urothelial carcinoma in real-world practice: A multicenter retrospective study. Narita, T., Hatakeyama, S., Numakura, K., et al.[2021]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, showed a strong antitumor effect in a 70-year-old female patient with unresectable bladder cancer, but it also led to a grade 3 asthma attack as an immune-related adverse event.

The patient's asthma was linked to changes in immune cell markers, specifically increased CTLA-4 and TIM-3 in CD4+ T cells and a rise in Th17 cells, suggesting that these immune responses could be indicators of both adverse effects and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of bronchial asthma as an immune-related adverse event of pembrolizumab treatment for bladder cancer: A case report. Hamada, K., Yoshimura, K., Oshinomi, K., et al.[2022]

In a study of 69 patients with advanced urothelial carcinoma who received pembrolizumab after failing platinum-based chemotherapy, the overall response rate (ORR) was 23.2%, indicating some efficacy of the treatment.

The organ-specific response rates varied, with the highest response observed in lung metastases (31.3%) and the lowest in primary tumor sites (7.1%), suggesting that different tumor locations may respond differently to pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Organ-Specific Tumor Response to Pembrolizumab in Advanced Urothelial Carcinoma After Platinum-Based Chemotherapy. Furubayashi, N., Negishi, T., Sakamoto, N., et al.[2022]

In a phase 2 study involving 370 patients with advanced urothelial cancer who were ineligible for cisplatin-based chemotherapy, first-line treatment with pembrolizumab resulted in a 24% objective response rate, with 83% of these responses ongoing at a median follow-up of 5 months.

Pembrolizumab demonstrated acceptable safety, with only 10% of patients experiencing serious treatment-related adverse events, making it a viable treatment option for patients with significant comorbidities or poor prognostic factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Balar, AV., Castellano, D., O'Donnell, PH., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a study of 78 patients with advanced urothelial carcinoma treated with pembrolizumab, the median overall survival was 7.3 months, and the estimated survival rate at 6 months was 61.5%, indicating its efficacy in a real-life setting.

The treatment was generally well-tolerated, with the most common side effects being fatigue and gastrointestinal issues, but no severe adverse events occurred in more than 5% of patients, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Benefit of Pembrolizumab in Advanced Urothelial Cancer Patients in Real-Life Setting: An Efficacy and Safety Monocentric Study. Dang, E., Vallée, A., Lepage-Seydoux, C., et al.[2022]

In the PURE-01 study involving 50 patients with muscle-invasive bladder carcinoma, neoadjuvant treatment with pembrolizumab resulted in a pathologic complete response (pT0) in 42% of patients, demonstrating its efficacy as a pre-surgery immunotherapy.

The study found that patients with high PD-L1 expression (CPS ≥ 10%) had a significantly higher rate of pT0 (54.3%) compared to those with lower expression (13.3%), suggesting that pembrolizumab may be particularly effective in patients with PD-L1-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. Necchi, A., Anichini, A., Raggi, D., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor used for treating metastatic bladder cancer, can lead to significant immune-related adverse events (IRAEs), such as lichenoid skin eruptions.

In this case, an elderly woman experienced a cutaneous IRAE that effectively responded to high-dose intravenous glucocorticoids, highlighting the need for monitoring and managing side effects in patients undergoing immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor lichenoid eruption due to pembrolizumab. McCormick, BJ., Zieman, D., West-Santos, C., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04701918

Cryoablation With Pembrolizumab Or Avelumab In ... This research study is examining the effectiveness of pembrolizumab plus cryoablation or aveluma plus cryoablation on people with urothelial carcinoma, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6452591/

Pembrolizumab in the treatment of locally advanced or ... Pembrolizumab, a highly specific, monoclonal antibody directed against PD-1, has demonstrated clinical efficacy as well as a favorable toxicity profile.

3. withpower.com withpower.com/trial/phase-3-urinary-bladder-neoplasms-5-2021-95573

Pembrolizumab + Cryoablation for Bladder Cancer What data supports the effectiveness of the treatment Pembrolizumab + Cryoablation for Bladder Cancer? Pembrolizumab (Keytruda) has been approved by the FDA ...

4. merck.com merck.com/news/mercks-keytruda-pembrolizumab-significantly-improved-disease-free-survival-dfs-as-adjuvant-therapy-versus-observation-in-high-risk-patients-with-localized-muscle-invasive-and-locall/

Merck's KEYTRUDA® (pembrolizumab) Significantly ... “In this trial, adjuvant pembrolizumab [KEYTRUDA] reduced the risk of disease recurrence or death from any cause by 31% versus observation, demonstrating the ...

5. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/265581

Cryoablation With Pembrolizumab Or Avelumab In ... This research study is examining the effectiveness of pembrolizumab plus cryoablation or aveluma plus cryoablation on people with urothelial ...

6. bcan.org bcan.org/clinicaltrials/pembrolizumab-and-cryoablation-in-urothelial-carcinoma/

Pembrolizumab And Cryoablation In Urothelial Carcinoma This research study is examining the effectiveness of pembrolizumab plus cryoablation or aveluma plus cryoablation on people with urothelial carcinoma, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10167412/

Cryoablation inhibits the recurrence and progression of ... This study revealed endoscopic cryoablation is an efficient and safe therapy for bladder tumour treatment.

8. dana-farber.org dana-farber.org/clinical-trials/20-531

A Multicenter, Single-Arm Open Label Phase II Trial of ... This research study is examining the effectiveness of pembrolizumab plus cryoablation or aveluma plus cryoablation on people with urothelial carcinoma, ...