Pembrolizumab + Gemcitabine for Bladder Cancer

Not currently recruiting at 453 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antibiotics, Steroids, Immunosuppressants, others

Disqualifiers: Autoimmune diseases, Active infection, CNS metastases, 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: 16

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding pembrolizumab, an immunotherapy drug, to gemcitabine, a chemotherapy drug, can more effectively treat bladder cancer that hasn't responded to BCG treatment. The aim is to determine if this combination can prevent cancer recurrence longer than gemcitabine alone. Individuals with non-muscle invasive bladder cancer who have tried BCG but still have high-grade tumors might be suitable candidates, particularly if they cannot or choose not to have their bladder removed. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received certain treatments like systemic anti-cancer therapy or radiotherapy within specific timeframes before joining the trial. It's best to discuss your current medications with the trial team.

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

Research shows that patients usually tolerate the combination of pembrolizumab and gemcitabine well. In other studies, individuals with bladder cancer who received this combination reported manageable side effects. Some studies have shown encouraging results, with an 88% success rate in early tests. This indicates that most people can undergo the treatment without serious side effects. However, as with any treatment, side effects can occur, so discussing any concerns with the trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab and gemcitabine for bladder cancer because it offers a novel approach by integrating an immune checkpoint inhibitor with a chemotherapy agent. Pembrolizumab works by blocking the PD-1 pathway, boosting the body's immune response against cancer cells, a mechanism distinct from standard chemotherapy treatments. When paired with gemcitabine, which is typically administered directly into the bladder, this combination may enhance the overall effectiveness and potentially lead to better outcomes. This approach not only maximizes the immune system's ability to fight cancer but also maintains localized treatment focus, which might reduce systemic side effects compared to traditional treatments.

What evidence suggests that adding pembrolizumab to gemcitabine might be an effective treatment for bladder cancer?

This trial will evaluate the combination of pembrolizumab and gemcitabine for treating bladder cancer. Studies have shown that using pembrolizumab, a type of immunotherapy, with gemcitabine, a chemotherapy drug, holds promise for treating bladder cancer. Research indicates that pembrolizumab helps the body's immune system attack cancer cells, while gemcitabine stops cancer cells from growing and spreading. Together, these treatments have produced positive results in other studies involving bladder cancer. Specifically, early findings suggest this combination can delay cancer's return in patients who did not respond to previous treatments. ^{1 4 6 7 8}

Who Is on the Research Team?

Michael E Woods

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

This trial is for adults with high-grade non-muscle invasive bladder cancer that hasn't responded to BCG treatment. Candidates must have had all visible tumors removed, not be pregnant or breastfeeding, agree to birth control use, and have proper organ function. Those unfit for radical cystectomy or refusing it can join. People with certain infections, recent radiation therapy to the lungs, active autoimmune diseases, other cancers within three years, or previous treatments with similar drugs are excluded.

Inclusion Criteria

Your platelet count is at least 100,000 per cubic millimeter.

My recent scans show no signs of cancer spread in my abdomen or pelvis.

Your hemoglobin level is at least 9.0 grams per deciliter.

Exclusion Criteria

I have a history of hepatitis B or an active hepatitis C infection.

I have active brain metastases or cancer in the lining of my brain.

I haven't had any cancer treatment or experimental drugs in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive pembrolizumab IV and gemcitabine intravesically. Treatment repeats every 3 weeks for 4 cycles.

12 weeks

4 visits (in-person)

Maintenance

Patients with no evidence of disease after induction receive pembrolizumab IV and gemcitabine intravesically. Treatment repeats every 3 weeks for 12 cycles.

36 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up every 3 months for 2 years, then every 6 months for 3 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine Hydrochloride
• Pembrolizumab

Trial Overview The study is testing if adding pembrolizumab (an immunotherapy drug) to gemcitabine (a chemotherapy drug) improves outcomes in patients whose bladder cancer has not improved after BCG treatment. Pembrolizumab helps the immune system fight cancer while gemcitabine works by killing or stopping tumor cells from growing.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab, gemcitabine hydrochloride) Experimental Treatment 8 Interventions

INDUCTION: Patients receive pembrolizumab IV over 25-40 minutes on day 1 of cycles 1-4. Patients also receive gemcitabine hydrochloride intravesically on days 1, 8 and 15 of cycles 1 and 2. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Beginning cycle 5, patients with no evidence of disease after induction receive pembrolizumab IV over 25-40 minutes and gemcitabine intravesically on day 1 of each cycle. Treatment repeats every 3 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients with T1 tumors undergo a re-staging TURBT within 60 days of registration. Patients also undergo urine and blood sample collection, bladder biopsy, cystoscopy, CT and MRI throughout the study.

Gemcitabine Hydrochloride is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Non-small cell lung cancer
• Pancreatic cancer
• Breast cancer
• Ovarian cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Non-small cell lung cancer
• Breast cancer
• Ovarian cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Non-small cell lung cancer
• Breast cancer
• Ovarian cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Non-small cell lung cancer
• Breast cancer
• Ovarian cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Pembrolizumab significantly improves survival and quality of life for patients with advanced urothelial cancer who cannot tolerate cisplatin-based chemotherapy, offering an increase of approximately 2.11 to 2.16 years in overall survival and 1.71 to 1.75 quality-adjusted life years (QALYs) compared to standard treatments like carboplatin plus gemcitabine and gemcitabine monotherapy.

Despite being associated with higher costs (an increase of €90,520 compared to carboplatin plus gemcitabine), pembrolizumab is considered cost-effective at a threshold of €100,000/QALY, making it a viable first-line treatment option for this patient population in Sweden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. Patterson, K., Prabhu, V., Xu, R., et al.[2022]

In a study of 39 patients with muscle-invasive bladder cancer, the combination of gemcitabine, cisplatin, and the immune checkpoint inhibitor pembrolizumab was effective, achieving pathologic downstaging in 56% of patients and complete pathologic response in 36%.

The treatment was generally safe, with common side effects including thrombocytopenia, anemia, and neutropenia, but no severe immune-related adverse events were reported, indicating a manageable safety profile for this neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer. Rose, TL., Harrison, MR., Deal, AM., et al.[2022]

The current chemotherapy regimen for metastatic bladder cancer, which includes cisplatin, methotrexate, vinblastine, and doxorubicin, shows limited impact on survival and is associated with significant toxicity.

Gemcitabine, a novel nucleoside analogue, has demonstrated promising response rates of up to 33% in phase II studies and is well tolerated, suggesting it may be a safer and effective alternative for treating bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic bladder cancer: advances in treatment. Stadler, WM., Kuzel, TM., Raghavan, D., et al.[2022]

In a phase II trial involving 51 patients with muscle-invasive bladder cancer, the combination of nivolumab and gemcitabine/cisplatin (N+GC) was well tolerated and resulted in a clinical complete response in 59% of patients, indicating its potential effectiveness as a neoadjuvant treatment.

The treatment led to a pathologic complete response in 24% of patients overall and 35% among those who underwent radical cystectomy, suggesting that N+GC can achieve significant tumor reduction before surgery, regardless of the patients' PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder. Kim, H., Jeong, BC., Hong, J., 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]

In the Phase III KEYNOTE-045 trial, pembrolizumab significantly improved overall survival in patients with second-line metastatic urothelial carcinoma compared to standard treatments like docetaxel, paclitaxel, and vinflunine.

Early results from the Phase II KEYNOTE-052 trial suggest that pembrolizumab is effective for first-line treatment in patients with metastatic urothelial carcinoma who are not eligible for cisplatin, leading to its FDA approval for these indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the treatment of advanced urothelial cancer. Lundgren, KT., Farina, MS., Bellmunt, J.[2018]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.4509

Long-term outcomes of pembrolizumab (pembro) in ... TMT combined with pembro was well tolerated and continues to show promising early outcomes data. A large phase 3 trial is underway to further explore this ...

2. 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8560445/

Successful treatment of metastatic bladder cancer by ... We report a successful case in which gemcitabine‐cisplatin re‐challenge after pembrolizumab therapy was effective in metastatic bladder cancer.

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. nejm.org nejm.org/doi/full/10.1056/NEJMoa1613683

Pembrolizumab as Second-Line Therapy for Advanced ... Because the median overall survival with second-line therapy is only 6 to 7 months, effective options are needed in patients with previously ...

6. urotoday.com urotoday.com/conference-highlights/asco-2021/asco-2021-bladder-cancer/130057-asco-2021-pembrolizumab-in-combination-with-gemcitabine-and-concurrent-hypofractionated-radiation-therapy-as-bladder-sparing-treatment-for-muscle-invasive-bladder-cancer-a-multicenter-phase-2-trial.html

ASCO 2021: Pembrolizumab in Combination With ... Pembrolizumab added to hypofractionated radiotherapy and twice weekly gemcitabine was well-tolerated with promising efficacy in this early analysis: 88% rate of ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04241185

NCT04241185 | Efficacy and Safety of Pembrolizumab (MK ... Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Muscle-invasive Bladder Cancer (MIBC) (MK ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.4504

Pembrolizumab (pembro) in combination with gemcitabine ... Pembro has shown activity in MIBC in the neoadjuvant setting and may combine well with TMT to improve outcomes. This trial evaluated the safety ...