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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments—pembrolizumab (an immunotherapy drug), gemcitabine (a chemotherapy drug), and radiation therapy—to evaluate their effectiveness for bladder cancer that has invaded the muscle. It targets individuals with muscle-invasive urothelial cancer who cannot or choose not to have their bladder removed. Participants must have a confirmed diagnosis of this bladder cancer type and be willing to provide tissue samples for study. The trial aims to find a more effective treatment option for those meeting these criteria. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that combining pembrolizumab with gemcitabine and radiation therapy is generally safe. Past patients have tolerated this combination well for treating bladder cancer. Some studies mention side effects such as tiredness, nausea, or skin reactions, but these are usually manageable. Pembrolizumab, already approved for other types of cancer, has a strong safety record. Combining it with gemcitabine and radiation may enhance effectiveness without major safety concerns. Prospective participants should consult their doctor to understand what to expect and determine if joining a trial is suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab, gemcitabine, and radiation therapy for bladder cancer because it brings a novel approach to treatment. Unlike traditional methods that often rely solely on surgery or chemotherapy, this combination leverages pembrolizumab, an immunotherapy drug that helps the immune system recognize and attack cancer cells more effectively. The addition of gemcitabine, a chemotherapy agent, and radiation therapy is designed to enhance the overall effectiveness, potentially leading to better outcomes. This multi-front attack not only targets cancer cells directly but also supports the body's natural defenses, offering a promising alternative to existing treatment options.

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

This trial will evaluate the combination of pembrolizumab, gemcitabine, and radiation therapy for treating muscle-invasive bladder cancer. Research has shown that combining pembrolizumab with gemcitabine and radiation therapy may be effective. In earlier studies, pembrolizumab reduced the risk of cancer recurrence or death by 31% compared to monitoring alone. Over time, this combination has helped preserve the bladder, potentially avoiding the need for bladder removal. The combination of immunotherapy, such as pembrolizumab, and radiation appears to improve patient outcomes. These findings suggest that this treatment could be a viable option for those who cannot or do not want to undergo major surgery. ^{1 2 3 4 5}

Who Is on the Research Team?

Minas Economides, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02621151

Study Details | NCT02621151 | Pembrolizumab (MK3475), ... This trial is to assess the efficacy of pembrolizumab (MK3475) added to concurrent radiation and gemcitabine in the management of patients with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04241185

NCT04241185 | Efficacy and Safety of Pembrolizumab (MK ... Participants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by ...

3. merck.com merck.com/news/mercks-keytruda-pembrolizumab-significantly-improved-disease-free-survival-dfs-as-adjuvant-therapy-versus-observation-in-high-risk-patients-with-localized-muscle-invasive-and-locall/

Merck's KEYTRUDA® (pembrolizumab) Significantly ... “In this trial, adjuvant pembrolizumab [KEYTRUDA] reduced the risk of disease recurrence or death from any cause by 31% versus observation, demonstrating the ...

4. urotoday.com urotoday.com/conference-highlights/asco-2023/asco-2023-bladder-cancer/144881-asco-2023-long-term-outcomes-of-pembrolizumab-in-combination-with-gemcitabine-and-concurrent-hypofractionated-radiation-therapy-as-bladder-sparing-treatment-for-muscle-invasive-urothelial-cancer-of-the-bladder-a-multicenter-phase-2-trial.html

ASCO 2023: Long-Term Outcomes of Pembrolizumab in ... A phase 2 trial assessing long-term outcomes of pembrolizumab in combination with gemcitabine and concurrent hypofractionated radiation therapy as bladder ...

5. 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.