Immune Checkpoint Inhibitors + Propranolol for Bladder Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Bassel Nazha, MD, MPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Emory University

Must be taking: Immune checkpoint inhibitors

Must not be taking: Beta blockers

Disqualifiers: Cardiovascular disease, Uncontrolled illness, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This research study is an open label study designed to evaluate the safety and translational correlative changes of the combination of propranolol hydrochloride and immune checkpoint inhibitors (ICI) in subjects with urothelial carcinoma.

Will I have to stop taking my current medications?

If you are currently taking a beta blocker (a type of heart medication), you will need to stop it at least 14 days before starting the trial and switch to a different type of medication. For other medications, the trial protocol does not specify if you need to stop them.

What data supports the effectiveness of the drug combination of immune checkpoint inhibitors and propranolol for bladder cancer?

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating certain types of bladder cancer that do not respond to BCG therapy, showing its effectiveness in this area. Additionally, studies have shown pembrolizumab to be effective as a treatment for muscle-invasive bladder cancer, both alone and in combination with other drugs. ^{1 2 3 4 5}

Is the combination of immune checkpoint inhibitors and propranolol safe for humans?

Pembrolizumab, an immune checkpoint inhibitor, has been studied for safety in bladder cancer and is generally considered safe, though it can cause immune-related side effects. Propranolol, a beta-blocker, is widely used for heart conditions and is generally safe, but combining it with pembrolizumab specifically for bladder cancer needs more research to fully understand the safety profile. ^{1 2 6 7 8}

How is the drug pembrolizumab combined with propranolol unique for bladder cancer treatment?

This treatment is unique because it combines pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with propranolol, a beta-blocker typically used for heart conditions, potentially enhancing the immune response against bladder cancer. ^{1 2 3 5 6}

Eligibility Criteria

Adults with urothelial carcinoma eligible for Pembrolizumab, Avelumab, or Nivolumab treatment can join. They should be relatively healthy (ECOG ≤2), have a life expectancy over 12 weeks, and proper organ/marrow function. Women must test negative for pregnancy and use birth control. Participants need to have finished previous cancer treatments at least 4 weeks prior and not have severe heart issues or other illnesses that could interfere with the trial.

Inclusion Criteria

I am either male or female.

I am 18 years old or older.

I am a woman who can have children, not pregnant, and agree to use birth control.

Exclusion Criteria

You have had allergic reactions to similar medications in the past.

I cannot take beta blocker medications due to health reasons.

I am currently taking a beta blocker and cannot safely switch to another medication.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immune checkpoint inhibitors with or without propranolol hydrochloride. Treatment continues until disease progression or unacceptable toxicity.

Up to 2 years

Every 2-4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

2 years

30 days post-treatment, then every 12 weeks

Treatment Details

Interventions

• Pembrolizumab (Checkpoint Inhibitor)
• Propranolol Hydrochloride (Beta Blocker)

Trial Overview The study is testing if adding Propranolol Hydrochloride to immune checkpoint inhibitors like Pembrolizumab, Avelumab, or Nivolumab improves outcomes in urothelial carcinoma patients. It's an open-label trial where everyone knows what treatment they're getting.

Participant Groups

Group I: Treatment (propranolol hydrochloride, immune checkpoint inhibitor) Experimental Treatment 4 Interventions

The specific ICI that the subject would receive will be dependent on the clinical need and associated FDA approval.

Group II: Treatment (immune checkpoint inhibitor) Experimental Treatment 3 Interventions

The specific ICI that the subject would receive will be dependent on the clinical need and associated FDA approval.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Emory University Hospital/Winship Cancer Institute Atlanta, GA

Who Is Running the Clinical Trial?

Emory University Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021] The FDA approved pembrolizumab (Keytruda) for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or chose to not undergo cystectomy.

2. United States pubmed.ncbi.nlm.nih.gov

Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer. [2022] To evaluate the safety and efficacy of gemcitabine and cisplatin in combination with the immune checkpoint inhibitor pembrolizumab as neoadjuvant therapy before radical cystectomy (RC) in muscle-invasive bladder cancer.

3. United States pubmed.ncbi.nlm.nih.gov

Effectiveness and safety profile of pembrolizumab for metastatic urothelial cancer: A retrospective single-center analysis in Japan. [2022] The paradigm of medical treatment for metastatic urothelial carcinoma is dramatically changing through the introduction of pembrolizumab.

4. United States 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. [2021] To determine the activity of pembrolizumab as neoadjuvant immunotherapy before radical cystectomy (RC) for muscle-invasive bladder carcinoma (MIBC) for which standard cisplatin-based chemotherapy is poorly used.

5. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Molecular Subtyping and Immune Infiltration on Pathological Response and Outcome Following Neoadjuvant Pembrolizumab in Muscle-invasive Bladder Cancer. [2021] The PURE-01 study (NCT02736266) evaluated the use of pembrolizumab before radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC).

6. United States pubmed.ncbi.nlm.nih.gov

PemBla: A Phase 1 study of intravesical pembrolizumab in recurrent non-muscle-invasive bladder cancer. [2023] This study aimed to investigate the anti-PD-1 inhibitor pembrolizumab as a potential agent for use in non-muscle-invasive bladder cancer (NMIBC) by conducting a Phase 1 safety run-in study to assess the safety and tolerability of intravesical pembrolizumab after transurethral resection of the bladder tumour (TURBT).

7. Switzerland pubmed.ncbi.nlm.nih.gov

Association of Immune-Related Adverse Events with Pembrolizumab Efficacy in the Treatment of Advanced Urothelial Carcinoma. [2020] Immune-related adverse events (irAEs) have been associated with the efficacy of programmed cell death protein 1 (PD-1) inhibitors in patients with urothelial cancer. We therefore evaluated the relationship between irAEs and pembrolizumab efficacy in urothelial cancer patients.

8. New Zealand pubmed.ncbi.nlm.nih.gov

Association Between Immune-Related Adverse Events and Efficacy and Changes in the Relative Eosinophil Count Among Patients with Advanced Urothelial Carcinoma Treated by Pembrolizumab. [2022] To evaluate the association between immune-related adverse events (irAEs) and the clinical outcomes and also between irAEs and the post-treatment changes in the relative eosinophil count (REC) in advanced urothelial carcinoma (UC) patients treated with pembrolizumab.