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

Trial Summary

What is the purpose of this trial?

The primary objective of this Phase I study is to establish the safety of adjuvant concurrent immunotherapy and radiation therapy for urothelial bladder cancer.

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.

What data supports the effectiveness of combining immunotherapy and radiotherapy for bladder cancer?

Research shows that combining immunotherapy with radiotherapy can slow tumor growth and improve survival in bladder cancer. This combination not only helps the treated area but may also trigger a broader immune response that affects other tumors, potentially leading to better overall outcomes. ^{1 2 3 4 5}

Is the combination of immunotherapy and radiotherapy generally safe for humans?

Research suggests that combining immunotherapy with radiotherapy does not lead to excessive harmful effects, even when high doses of radiotherapy are used. Clinical trials have shown that this combination is generally well-tolerated, with no significant increase in toxicity. ^{1 3 6 7 8}

How is the treatment of combining immunotherapy and radiotherapy unique for bladder cancer?

This treatment is unique because it combines radiotherapy, which not only kills cancer cells locally but also stimulates the immune system, with immunotherapy, which helps the immune system attack cancer cells. This combination can lead to a stronger anti-cancer response both at the site of the tumor and in other parts of the body, potentially improving outcomes for patients with bladder cancer. ^{1 2 5 9 10}

Research Team

John Christodouleas, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

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

PD-1/PD-L1 Immune Checkpoint Inhibition with Radiation in Bladder Cancer: In Situ and Abscopal Effects. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Is There a Benefit of Combining Immunotherapy and Radiotherapy in Bladder Cancer? [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapy Combined With Radiation Therapy for Genitourinary Malignancies. [2021]

4. Netherlands 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). [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

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

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

Radiation Therapy and Immune Modulation. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Combining radiation and immunotherapy for synergistic antitumor therapy. [2021]

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

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. [2022]

9. France pubmed.ncbi.nlm.nih.gov

Combination of radiotherapy and immune treatment: First clinical data. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti-tumor immune response. [2021]