Pembrolizumab + Gemcitabine for Bladder Cancer

Recruiting at 245 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

161 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effect of adding pembrolizumab to gemcitabine in treating patients with non-muscle invasive bladder cancer whose cancer does not respond to Bacillus Calmette-Guerin (BCG) treatment. Chemotherapy drugs, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the patient's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding pembrolizumab to gemcitabine may delay the return of BCG-unresponsive bladder cancer for longer period compared to gemcitabine alone.

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.

What data supports the effectiveness of the drug combination Pembrolizumab and Gemcitabine for bladder cancer?

Pembrolizumab has been shown to improve survival in patients with advanced urothelial cancer and is approved for use in certain types of bladder cancer. Gemcitabine is commonly used in combination with other drugs for bladder cancer treatment, suggesting potential effectiveness when combined with Pembrolizumab. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Gemcitabine safe for humans?

Pembrolizumab and Gemcitabine have been studied for safety in various conditions, including bladder cancer. Gemcitabine was well tolerated in studies with few side effects, and Pembrolizumab has been approved by the FDA for certain types of bladder cancer, indicating a recognized safety profile. ^{1 2 3 4 6}

How is the drug Pembrolizumab + Gemcitabine unique for bladder cancer treatment?

Pembrolizumab + Gemcitabine is unique because it combines an immune checkpoint inhibitor (Pembrolizumab) with chemotherapy (Gemcitabine), offering a novel approach for patients who cannot tolerate traditional cisplatin-based treatments. This combination leverages the immune system to fight cancer while also using chemotherapy to target cancer cells directly. ^{1 2 3 4 5}

Research Team

Michael E Woods

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

References

1. United States 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. [2022]

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

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

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

Pembrolizumab in the treatment of advanced urothelial cancer. [2018]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. [2022]

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

Metastatic bladder cancer: advances in treatment. [2022]