Romidepsin + Durvalumab for Bladder Cancer

Overseen By Robin Neubauer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immune checkpoint inhibitors, CYP3A modulators

Disqualifiers: Autoimmune disease, Cardiac diseases, others

Stay on Your Current Meds You can continue your current medications while participating

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, romidepsin and durvalumab, to determine their safety and effectiveness in treating muscle invasive bladder cancer. It targets patients unable to receive standard cisplatin chemotherapy due to health reasons. Suitable candidates include those with muscle invasive bladder cancer who cannot take cisplatin because of conditions like kidney problems or hearing impairment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking medications that are strong inhibitors or inducers of CYP3A, or if you are on concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment.

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

Research has shown that the combination of romidepsin and durvalumab might be safe and manageable for patients with muscle invasive bladder cancer. Durvalumab has been used in patients with various cancers, including bladder cancer. Some patients have experienced side effects such as loss of appetite and diarrhea.

Other studies have found this combination potentially safe for treating localized bladder cancer. The trials assessed patient tolerance using standard safety checks. While these results are encouraging, the trial remains in an early stage, and researchers continue to gather information on patient tolerance for these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Romidepsin and Durvalumab for bladder cancer because they introduce a unique combination approach. Unlike standard treatments like chemotherapy and immunotherapy, Romidepsin is a histone deacetylase inhibitor, which can modify the expression of genes involved in cancer growth, potentially making cancer cells more susceptible to the immune system. Durvalumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This combo could offer a two-pronged attack against cancer, enhancing the body's ability to fight the disease while potentially overcoming resistance to existing therapies.

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

Research has shown that durvalumab effectively treats patients with metastatic urothelial carcinoma, a type of bladder cancer. In earlier studies, some patients responded to durvalumab in about six weeks. This trial explores the combination of durvalumab with romidepsin at different dose levels to determine its safety and effectiveness for localized muscle invasive bladder cancer (MIBC). While durvalumab is more familiar, researchers are testing romidepsin to see if it can enhance the treatment's effects. This combination aims to attack cancer cells in a new way, offering hope for better results. ^{1 2 3 4 6}

Who Is on the Research Team?

Jingsong Zhang, MD, PhD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with muscle invasive bladder cancer who cannot receive cisplatin. Participants should not have had prior treatments for their condition and must be fit enough to undergo the procedures involved in the study.

Inclusion Criteria

Willing to provide tumor tissue, blood, and urine samples for research.

Participants must have adequate organ and marrow function as defined below: Hemoglobin ≥ 9.0 g/dL; Absolute neutrophil count (ANC) ≥ 1500/mcL; Platelet count ≥100,000/mcL; Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN); total bilirubin must be < 3 x ULN for patients with Gilberts syndrome; AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal; Measured creatinine CL >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.

Patient must have a life expectancy of at least 12 weeks.

Exclusion Criteria

Patients unwilling or unable to comply with the protocol.

Patients who have known diagnosis of human immunodeficiency virus (HIV) infection. Testing is not required in absence of clinical suspicion.

Patients with a known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravesical romidepsin and durvalumab. Romidepsin is administered at varying dose levels on C1D1, and durvalumab is given at a fixed dose every 4 weeks on C1D1 and C2D1.

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of pathologic response and relapse-free survival.

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Romidepsin

Trial Overview The study tests a combination of two drugs, romidepsin (administered directly into the bladder) and durvalumab (given intravenously), to see if they are safe and effective when given before surgery to remove bladder tumors.

How Is the Trial Designed?

Group I: Dose Level 3 Experimental Treatment 2 Interventions

Romidepsin Level 3: 2.0 ng/m on C1D1. Durvalumab: The recommended fixed dose of durvalumab is 1500 mg every 4 weeks and will be given on C1D1 and C2D1.

Group II: Dose Level 2 Experimental Treatment 2 Interventions

Romidepsin Level 2: 0.4 ng/ml on C1D1. Durvalumab: The recommended fixed dose of durvalumab is 1500 mg every 4 weeks and will be given on C1D1 and C2D1.

Group III: Dose Level 1 Experimental Treatment 2 Interventions

Romidepsin Level 1: 0.2 ng/ml on C1D1. Durvalumab: The recommended fixed dose of durvalumab is 1500 mg every 4 weeks and will be given on C1D1 and C2D1.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a study of patients with metastatic urothelial carcinoma, treatment with durvalumab led to significant improvements in health-related quality of life (HRQOL) and disease-related symptoms, as measured by the FACT-Bl and EORTC QLQ-C30 questionnaires.

The improvements in patient-reported outcomes were correlated with better tumor shrinkage and reductions in inflammatory biomarkers, suggesting that durvalumab not only helps manage cancer symptoms but may also positively influence systemic inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and inflammatory biomarkers in patients with locally advanced/metastatic urothelial carcinoma treated with durvalumab in phase 1/2 dose-escalation study 1108. O'Donnell, PH., Arkenau, HT., Sridhar, SS., et al.[2021]

In a phase I trial involving Japanese patients with advanced cancer, tremelimumab was found to be safe and well-tolerated, with no dose-limiting toxicities observed in the initial dosing phase, although 75% of patients reported treatment-related adverse events.

When combined with durvalumab, tremelimumab showed a manageable safety profile, with only two instances of serious adverse events (Grade 4 myasthenia gravis and hyperglycemia), indicating that the combination therapy can be administered with careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Tremelimumab Monotherapy or in Combination With Durvalumab in Japanese Patients With Advanced Solid Tumors or Malignant Mesothelioma. Fujiwara, Y., Takahashi, Y., Okada, M., et al.[2022]

The SUBDUE-1 trial is a phase I study evaluating the safety and immunological efficacy of sub-urothelial injections of durvalumab in adults with muscle-invasive or high-risk non-muscle-invasive bladder cancer, involving three dose levels (25, 75, 150 mg) to determine the optimal dose for future trials.

If successful, this local administration method may reduce tumor recurrence and progression while minimizing immunological side effects and costs compared to traditional systemic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I open label dose-escalation study to evaluate the tolerability, safety and immunological efficacy of sub-urothelial durvalumab injection in adults with muscle-invasive or high-risk non-muscle-invasive bladder cancer (SUBDUE-1, SUB-urothelial DUrvalumab injection-1 study): clinical trial protocol. Moe, A., Liow, E., Redfern, A., et al.[2021]

Durvalumab, a monoclonal antibody targeting PD-L1, showed a manageable safety profile in patients with advanced urothelial bladder cancer, with common side effects including fatigue and diarrhea, but no severe (grade 4 or 5) adverse events reported.

The treatment demonstrated a 31% overall response rate, with a significantly higher response of 46.4% in patients with PD-L1-positive tumors, indicating that PD-L1 expression may play a crucial role in the efficacy of durvalumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer. Massard, C., Gordon, MS., Sharma, S., et al.[2022]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

Thirteen clinical trials are currently investigating the use of immune checkpoint inhibitors as a treatment for high-risk non-muscle-invasive bladder cancer, particularly in patients who have not responded to Bacillus Calmette-Guérin (BCG) therapy.

Preliminary results from trials like SWOG S1605 and Keynote-057 indicate that checkpoint inhibitors, such as Pembrolizumab, show promising antitumor activity and are generally well-tolerated, suggesting they could be a viable alternative for patients with BCG-unresponsive bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoints inhibitors in the management of high-risk non-muscle-invasive bladder cancer. A scoping review. García-Perdomo, HA., Sánchez, AL., Spiess, PE.[2022]

Citations

1. withpower.com withpower.com/trial/phase-1-urinary-bladder-neoplasms-3-2025-661a3

Romidepsin + Durvalumab for Bladder Cancer Durvalumab has shown meaningful clinical activity in patients with metastatic urothelial carcinoma, a type of bladder cancer, as seen in Study 1108.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-03473

Intravesical Romidepsin in Combination with Durvalumab ... Giving intravesical romidepsin in combination with durvalumab may be safe, tolerable, and/or effective in treating patients with localized MIBC. Eligibility ...

3. moffitt.org moffitt.org/clinical-trials-and-studies/clinical-trial-22623/

Clinical Trial 22623 Primary Objective: To evaluate the safety of combination therapy using intravesical romidepsin and durvalumab according to Common Terminology Criteria for ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6452813/

Durvalumab for the management of urothelial carcinoma The median time to response was 6.3 weeks (95% CI, 5.6–12.1 weeks) in the 13 responding patients, and median duration of response has not been reached (range, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03161223

Study Details | NCT03161223 | Durvalumab in Different ... This study focuses on exploring rational combinations of these T-cell active agents in an effort to develop novel treatment platforms. Official Title. Phase 1/ ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12065394/

A Phase 2 Study of Durvalumab for Bacillus Calmette ... Durvalumab monotherapy conferred minimal efficacy in treating BCG-unresponsive CIS of the bladder, with 6mo complete response of 12%. Complement activation is a ...