Immunotherapy + Radiotherapy for Bladder Cancer

Overseen By Project Manager

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Abramson Cancer Center at Penn Medicine

Must be taking: Checkpoint inhibitors

Must not be taking: Chemotherapy, Investigational drugs

Disqualifiers: Inflammatory bowel disease, Neobladder, 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)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of combining immunotherapy and radiation therapy to treat bladder cancer. It targets individuals with urothelial bladder cancer who have undergone major surgery to remove the bladder and lymph nodes. The trial includes those showing no signs of disease recurrence but receiving immunotherapy post-surgery. Participants must not have had prior radiation in the pelvic region and must be eligible for radiation therapy. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative combination therapy.

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

You can continue taking your current non-investigational medications while participating in this trial.

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

Research shows that combining immunotherapy and radiation therapy for bladder cancer might be safe for many patients. Some studies have examined the safety of using these treatments simultaneously. The primary concern is whether patients will experience severe side effects, known as serious pelvic radiation-related issues.

Although detailed information on these side effects is not yet available, the research aims to determine if patients can tolerate this treatment combination. This approach is under investigation because earlier studies suggest that these treatments might work well together to combat cancer.

As this is an early-stage study, complete safety data might not yet be available. However, these treatments might already be safe when used individually, offering hope for their combined use. Patients should always discuss potential risks and benefits with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about combining immunotherapy and radiation therapy for bladder cancer because it offers a new approach compared to traditional treatments like surgery, chemotherapy, or radiation therapy alone. Unlike standard treatments that usually target the cancer directly, immunotherapy boosts the body's immune system to recognize and attack cancer cells. This concurrent treatment might enhance the effectiveness of radiation therapy by making cancer cells more susceptible to immune attack, potentially leading to better outcomes. By using both therapies at the same time, there's hope for a more powerful response against the cancer, with possibly fewer side effects than traditional chemotherapy.

What evidence suggests that concurrent immunotherapy and radiation therapy might be an effective treatment for bladder cancer?

Research has shown that combining immunotherapy and radiation therapy for bladder cancer, as studied in this trial, may improve treatment outcomes. Studies have found that this combination helps the immune system better locate and destroy cancer cells. Evidence suggests these treatments work more effectively together than separately. For patients with muscle-invasive bladder cancer, this approach might reduce tumor size and possibly avoid bladder removal. While these findings are encouraging, further research is needed to confirm these benefits. ^{1 2 4 6 7}

Who Is on the Research Team?

John Christodouleas, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for individuals with urothelial bladder cancer. Specific eligibility details are not provided, but typically participants would need to meet certain health standards and have a confirmed diagnosis of the condition being studied.

Inclusion Criteria

My bladder cancer is a specific type called urothelial carcinoma.

I have shown no signs of cancer returning in the last 3 months.

My cancer is at least stage T3 but has not spread to distant organs.

Exclusion Criteria

I have a history of inflammatory bowel disease.

I have or had another type of cancer besides the one being treated.

I had surgery for my condition but some of the disease remains.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive concurrent adjuvant immunotherapy and radiation therapy

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Concurrent Immunotherapy
• Concurrent Immunotherapy and Radiation Therapy

Trial Overview The study is testing the safety of combining immunotherapy with radiation therapy as an additional treatment (adjuvant therapy) after primary treatment for bladder cancer.

How Is the Trial Designed?

Group I: Concurrent Immunotherapy and Radiation Therapy Experimental Treatment 1 Intervention

Subjects will receive the standard of care procedures and follow-up for immunotherapy and radiation therapy. The part of this study that is research is receiving both of these treatments at the same time.

Concurrent Immunotherapy and Radiation Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Concurrent Immunotherapy and Radiation Therapy for:

• Urothelial bladder cancer

Approved in European Union as Concurrent Immunotherapy and Radiation Therapy for:

• Muscle-invasive bladder cancer

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Published Research Related to This Trial

Immunotherapy drugs have been recently approved for treating genitourinary cancers like bladder, renal, and prostate cancer, showing promise in enhancing treatment outcomes.

Combining immunotherapy with radiation therapy may improve tumor cell killing both at the targeted site and potentially at distant sites, known as the abscopal effect, making this combination a focus of ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy Combined With Radiation Therapy for Genitourinary Malignancies. Ukleja, J., Kusaka, E., Miyamoto, DT.[2021]

Immune checkpoint inhibitors have significantly improved treatment outcomes for metastatic urothelial cancer, but only about 20% of patients respond to anti-PD-1 therapy alone.

Combining radiotherapy with checkpoint inhibitors may enhance the immune response against tumors, potentially increasing the effectiveness of treatment, as suggested by early clinical trials and preclinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is There a Benefit of Combining Immunotherapy and Radiotherapy in Bladder Cancer? Wilkins, A., Ost, P., Sundahl, N.[2022]

The combination of pembrolizumab with chemoradiation for muscle-invasive bladder cancer (MIBC) was found to be feasible, with manageable toxicity, as only six patients experienced grade 3 or worse nonurinary adverse events out of 28 participants in the study.

The treatment showed promising efficacy, with an 88% complete response rate at 24 weeks post-chemoradiation, and favorable survival rates, including a 2-year distant metastasis-free survival rate of 78% and locoregional progression-free survival rate of 87%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with Chemoradiation as Treatment for Muscle-invasive Bladder Cancer: Analysis of Safety and Efficacy of the PCR-MIB Phase 2 Clinical Trial (ANZUP 1502). Weickhardt, A., Foroudi, F., Lawrentschuk, N., et al.[2023]

Combining radiotherapy with immunotherapies appears to be safe, as it does not lead to increased toxicity, even at definitive doses of radiotherapy.

Recent clinical trials, like the PACIFIC trial, have shown promising results regarding the safety and efficacy of these combinations, suggesting potential benefits such as abscopal effects, where treatment at one site affects distant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Therapy and Immune Modulation. Leeman, JE., Schoenfeld, JD.[2020]

Combining radiation therapy with immunotherapy shows great potential for enhancing cancer treatment, as preclinical studies suggest that radiation can make tumor cells more vulnerable to immune attacks.

Clinical trials have begun to support the idea that this combination can effectively boost antitumor immune responses, with ongoing studies exploring various therapeutic vaccines alongside radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining radiation and immunotherapy for synergistic antitumor therapy. Ferrara, TA., Hodge, JW., Gulley, JL.[2021]

The combination of radiation therapy and the immune checkpoint inhibitor anti-PD-L1 significantly slowed tumor growth in both treated and untreated bladder tumors in mice, indicating a strong therapeutic synergy (P < 0.001).

This combined treatment not only improved survival rates compared to either therapy alone (P = 0.02) but also altered the tumor microenvironment by increasing cytotoxic T cell activity and decreasing immunosuppressive factors, suggesting a potential abscopal effect in bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 Immune Checkpoint Inhibition with Radiation in Bladder Cancer: In Situ and Abscopal Effects. Rompré-Brodeur, A., Shinde-Jadhav, S., Ayoub, M., et al.[2020]

Combining radiotherapy with immune treatment shows strong potential for enhancing the immune response against cancer, as radiation can increase the expression of key molecules that help the immune system recognize and attack tumors.

Preliminary clinical studies suggest that this combination therapy can effectively control local tumors and even lead to regression of distant metastases without significantly increasing side effects compared to using each treatment alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of radiotherapy and immune treatment: First clinical data. De Ruysscher, D.[2018]

Combining radiotherapy (RT) with immunotherapy in muscle-invasive bladder cancer (MIBC) can enhance tumor control by inducing immunogenic cell death and increasing immune markers, suggesting a promising synergy between these treatments.

In localized MIBC, safety concerns exist with concurrent immunotherapy during hypofractionated RT, leading to a preference for neoadjuvant or adjuvant immunotherapy, while in metastatic cases, higher doses of RT combined with immunotherapy show the most efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti-tumor immune response. Daro-Faye, M., Kassouf, W., Souhami, L., et al.[2021]

In a study of 60 patients receiving combined immunotherapy and thoracic radiation therapy (iRT), no patients experienced severe grade ≥4 toxicities, indicating a favorable safety profile for this treatment approach.

While some patients did experience grade 3 toxicities, particularly pulmonary and hematologic issues, the overall short-term safety of iRT suggests it can be administered without significant risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. Verma, V., Cushman, TR., Selek, U., et al.[2022]

Immunotherapy combined with radiotherapy can enhance cancer treatment effectiveness, as radiation not only kills tumor cells but can also stimulate the immune system, potentially leading to systemic tumor control, known as the abscopal effect.

Clinical trials are exploring these combination therapies in both locally advanced and metastatic cancers to improve survival rates, indicating a promising approach for both curative and palliative treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Multimodal treatment concepts of local radiation therapy with immunotherapy : Rationale for combination therapy and possible clinical treatment strategies]. Eckert, F.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12088031/

Advancements in bladder cancer treatment: The synergy of ... New discoveries have shown that combining immunotherapy and radiation treatment may improve patient outcomes.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S187985002500147X

Combining Radiation Therapy With Immune Checkpoint ... New evidence indicates that combining RT and immunotherapy could have a synergistic effect in patients with urothelial cancer.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07061964

NCT07061964 | Combining Immunotherapy and Radiation ... Combining Immunotherapy and Radiation Therapy to Help Patients Avoid Bladder Removal After Treatment Shrinks Muscle Invasive Bladder Cancer, BRIGHT Trial.

4. practicalradonc.org practicalradonc.org/article/S1879-8500(25)00147-X/abstract

Combining Radiation Therapy With Immune Checkpoint ... This review aims to evaluate the efficacy and safety of combining immune checkpoint inhibitors (ICI) with RT in the treatment of non-metastatic MIBC.

5. oncotarget.com oncotarget.com/news/pr/combining-radiation-and-immunotherapy-shows-promise-for-bladder-cancer/

Combining Radiation and Immunotherapy Shows Promise ... The review explores how combining radiation and immunotherapy could improve outcomes by helping the immune system detect and destroy cancer cells more ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06586255

Adjuvant Concurrent Immunotherapy and Radiotherapy for ... Safety of concurrent adjuvant immunotherapy and radiation therapy. The primary study endpoint is acute grade 3 or higher pelvic radiation related toxicity.

7. ascopost.com ascopost.com/issues/november-10-2025/safety-and-benefit-of-radiation-therapy-for-high-risk-muscle-invasive-bladder-cancer/

Safety and Benefit of Radiation Therapy for High-Risk ... The rate of bladder cancer–specific survival at 2 years was 79.6% with radiation vs 65.0% with observation (HR = 0.59; 95% CI = 0.33–1.10; P = .