Pembrolizumab + Gemcitabine + Radiation for Bladder Cancer

Recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Prior chemotherapy, Autoimmune disease, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is to assess the efficacy of pembrolizumab (MK3475) added to concurrent radiation and gemcitabine in the management of patients with muscle-invasive urothelial cancer who are not candidates for or decline radical cystectomy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or any form of immunosuppressive therapy, you must stop these at least 7 days before starting the trial treatment.

What data supports the effectiveness of the treatment Pembrolizumab + Gemcitabine + Radiation for Bladder Cancer?

Research suggests that combining pembrolizumab (an immune therapy drug) with radiation can enhance the body's immune response against bladder cancer. Additionally, gemcitabine (a chemotherapy drug) with radiation has shown promise in treating bladder cancer, especially for patients who cannot undergo surgery. ^{1 2 3 4 5}

Is the combination of Pembrolizumab, Gemcitabine, and Radiation generally safe for humans?

The combination of pembrolizumab and radiation has been studied in various settings, showing it is generally well tolerated with no severe side effects reported in some trials. However, pembrolizumab can cause pneumonitis (lung inflammation) in a small percentage of patients, which is a potentially serious side effect. ^{1 2 4 6 7}

How is the treatment of pembrolizumab, gemcitabine, and radiation unique for bladder cancer?

This treatment is unique because it combines pembrolizumab, an immune therapy that helps the body's immune system attack cancer cells, with gemcitabine, a chemotherapy drug, and radiation therapy. This combination aims to enhance the immune response against the cancer, potentially leading to better outcomes than using these treatments separately. ^{1 2 5 8 9}

Research Team

Scot Niglio, MD

Principal Investigator

NYU Perlmutter Cancer Center

Eligibility Criteria

This trial is for adults with muscle-invasive urothelial bladder cancer who can't have or don't want a radical cystectomy. They must be in good health, not pregnant, agree to use contraception, and provide consent. People with certain allergies, recent investigational drug use, major surgery recovery, specific syndromes like Guillain-Barre or Stevens-Johnson Syndrome, active infections or conditions that could affect the trial's outcome are excluded.

Inclusion Criteria

I am using two birth control methods or am not able to have children, and will continue for 120 days after the study.

My bladder cancer is at a specific stage but hasn't spread to lymph nodes or other parts.

I have taken a pregnancy test within the last 72 hours and it was negative.

Exclusion Criteria

I have an active tuberculosis infection.

I am currently being treated for an infection.

I have a history of inflammatory bowel disease or scleroderma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Initial safety lead-in cohort of 3 to 6 patients is enrolled for assessing dose-limiting toxicities

3 weeks

Treatment

Participants receive Pembrolizumab, Gemcitabine, and concurrent hypofractionated radiation therapy

4 weeks

Multiple visits for IV administration and radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Long-term Follow-up

Monitoring for bladder-intact disease-free survival and metastasis-free survival

up to 5 years

Treatment Details

Interventions

• External Beam Radiation Therapy
• Gemcitabine
• Pembrolizumab
• Transurethral Resection of Bladder Tumor

Trial Overview The study tests if adding pembrolizumab (MK3475) to gemcitabine and radiation therapy improves outcomes for patients with bladder cancer who aren't undergoing surgery. Participants will receive these treatments concurrently to see how effective they are when combined.

Participant Groups

Group I: Pembrolizumab, Gemcitabine, and RT Experimental Treatment 4 Interventions

* Lead-in single dose Pembrolizumab 200 mg, intravenously (IV) * Transurethral Resection of Bladder Tumor (TURBT) at pre-RT (maximal) and completion of therapy (diagnostic) * External Beam Radiation Therapy (EBRT) - 52 Gy in 20 fractions over 4 weeks (1 fraction = 2.6 Gy) * Gemcitabine 27 mg/m\^2 IV twice weekly for 4 weeks concurrent with EBRT * Pembrolizumab 200 mg IV every 3 weeks for total 3 doses starting day 1 of EBRT

External Beam Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in United States as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in Canada as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in Japan as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in China as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in Switzerland as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

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]

In a study of 98 advanced urothelial cancer patients, those who received radiotherapy to the primary tumor showed a significantly higher objective response rate to pembrolizumab (65% vs 19%) compared to those who did not receive radiotherapy.

Patients who had prior radiotherapy also experienced better overall survival rates (77% vs 50% at 12 months), suggesting that radiotherapy may enhance the effectiveness of pembrolizumab in treating advanced urothelial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of radiotherapy to the primary tumor on the efficacy of pembrolizumab for patients with advanced urothelial cancer: A preliminary study. Fukushima, H., Kijima, T., Fukuda, S., et al.[2023]

In a phase I trial involving 44 patients with muscle-invasive bladder cancer who were ineligible for surgery, the maximum-tolerated dose of gemcitabine was determined to be 50 mg/m², with a recommended dose of 40 mg/m² for future studies, indicating a manageable safety profile.

The combination of gemcitabine and radiotherapy resulted in a 2-year locoregional failure rate of 32%, with 38% of patients maintaining an intact bladder and no recurrence, suggesting potential efficacy for this treatment approach in patients who cannot undergo surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined chemoradiotherapy with gemcitabine in patients with locally advanced inoperable transitional cell carcinoma of the urinary bladder and/or in patients ineligible for surgery: a phase I trial. De Santis, M., Bachner, M., Cerveny, M., et al.[2023]

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]

References

1. 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]

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

Impact of radiotherapy to the primary tumor on the efficacy of pembrolizumab for patients with advanced urothelial cancer: A preliminary study. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Combined chemoradiotherapy with gemcitabine in patients with locally advanced inoperable transitional cell carcinoma of the urinary bladder and/or in patients ineligible for surgery: a phase I trial. [2023]

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

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

5. England pubmed.ncbi.nlm.nih.gov

A phase I/II trial of fixed-dose stereotactic body radiotherapy with sequential or concurrent pembrolizumab in metastatic urothelial carcinoma: evaluation of safety and clinical and immunologic response. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Randomized Phase 1 Trial of Pembrolizumab with Sequential Versus Concomitant Stereotactic Body Radiotherapy in Metastatic Urothelial Carcinoma. [2019]

8. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of Combined Pembrolizumab and Pelvic Radiotherapy for Bladder Cancer With Rectal Metastases. [2023]

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

Combined-modality therapy with gemcitabine and radiation therapy as a bladder preservation strategy: long-term results of a phase I trial. [2022]