Pembrolizumab + Chemotherapy for Bladder Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Immunosuppressants, Steroids, Monoclonal antibodies, others

Disqualifiers: Immunodeficiency, Active TB, Autoimmune, 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: 1

Duration: 12 weeks

39 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate whether adding pembrolizumab (Keytruda) to the combination of gemcitabine and cisplatin will improve shrinkage of the tumor before having a cystectomy, for people with muscle-invasive bladder cancer (MIBC).

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

The trial does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial treatment, except for certain exceptions like inhaled or topical steroids.

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

Research shows that Pembrolizumab, when used with chemotherapy drugs like Cisplatin and Gemcitabine, can be effective for bladder cancer. In particular, Pembrolizumab has been shown to improve survival and quality of life in patients with advanced urothelial cancer, and it is approved for certain types of bladder cancer that do not respond to other treatments. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and chemotherapy safe for bladder cancer treatment?

The combination of Pembrolizumab with chemotherapy, including drugs like cisplatin and gemcitabine, has been studied for bladder cancer and is generally considered safe, though it can cause side effects like fatigue, low blood cell counts, and nausea. Pembrolizumab, an immune therapy, is well-tolerated and offers an alternative for patients who cannot use standard chemotherapy. However, patients should discuss potential side effects with their healthcare provider. ^{1 2 3 4 6}

What makes the drug combination of Pembrolizumab, Cisplatin, and Gemcitabine unique for bladder cancer treatment?

This drug combination is unique because it includes pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, alongside traditional chemotherapy drugs cisplatin and gemcitabine, offering a new option for patients who may not tolerate standard cisplatin-based therapies. ^{1 2 3 4 7}

Research Team

Matthew Milowsky, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with muscle-invasive bladder cancer who haven't had systemic chemotherapy for it. They must be fit enough for surgery, have a life expectancy over 3 months, and their cancer should not have spread beyond the bladder. Pregnant or breastfeeding women can't join, nor can those with certain other cancers, active infections, autoimmune diseases treated within the last 2 years, or recent use of immunosuppressants.

Inclusion Criteria

I've had recent scans of my chest and abdomen.

I am a suitable candidate for bladder removal surgery as determined by my urologist.

Consents to whole blood collection prior to initiating therapy and at cystectomy for support of correlative research studies

Exclusion Criteria

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I have an autoimmune disease treated with medication in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pembrolizumab, gemcitabine, and cisplatin for 4 cycles over 12 weeks

12 weeks

Pembrolizumab on day 1, cisplatin and gemcitabine on days 1 and 8 every 3 weeks

Cystectomy

Participants undergo cystectomy within 70 days after treatment

Up to 10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Cisplatin
• Gemcitabine
• Pembrolizumab

Trial Overview The study tests if adding pembrolizumab (Keytruda) to gemcitabine and cisplatin before surgery improves tumor shrinkage in bladder cancer patients. It's a phase 2 trial where all participants receive this combination as neoadjuvant therapy prior to having their bladders surgically removed.

Participant Groups

Group I: pembrolizumab, gemcitabine and cisplatin Experimental Treatment 1 Intervention

There is one arm in this study. Subjects will receive Pembrolizumab 200mg IV on day 1 in combination with cisplatin 35mg/m2 and gemcitabine 1000mg/m2 on day 1 and day 8 every 3 weeks for 4 cycles over 12 weeks.

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

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

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 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 phase 2 study involving 370 patients with advanced urothelial cancer who were ineligible for cisplatin-based chemotherapy, first-line treatment with pembrolizumab resulted in a 24% objective response rate, with 83% of these responses ongoing at a median follow-up of 5 months.

Pembrolizumab demonstrated acceptable safety, with only 10% of patients experiencing serious treatment-related adverse events, making it a viable treatment option for patients with significant comorbidities or poor prognostic factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Balar, AV., Castellano, D., O'Donnell, PH., 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 KEYNOTE-045 study involving 542 patients with advanced urothelial cancer, pembrolizumab significantly prolonged overall survival compared to standard chemotherapy, demonstrating its efficacy as a treatment option.

Patients receiving pembrolizumab experienced a longer time to deterioration in health-related quality of life (3.5 months) compared to those on chemotherapy (2.3 months), indicating that pembrolizumab not only improves survival but also maintains or enhances quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality-of-Life Analysis From KEYNOTE-045: A Phase III Study of Pembrolizumab Versus Chemotherapy for Previously Treated Advanced Urothelial Cancer. Vaughn, DJ., Bellmunt, J., Fradet, Y., et al.[2021]

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

Atezolizumab, an anti-PD-L1 monoclonal antibody, has shown durable responses in treating locally advanced and metastatic urothelial cancer, especially in patients who have failed platinum-based chemotherapy or are ineligible for cisplatin.

The treatment with atezolizumab has a more favorable toxicity profile compared to traditional cytotoxic chemotherapy, making it a promising option for patients with advanced bladder cancer, although further research is needed to identify additional predictive markers for response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. Crist, M., Balar, A.[2019]

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. 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]

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

First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. [2022]

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

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

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

Health-Related Quality-of-Life Analysis From KEYNOTE-045: A Phase III Study of Pembrolizumab Versus Chemotherapy for Previously Treated Advanced Urothelial Cancer. [2021]

6. Czech Republic pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. [2019]

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

Atezolizumab in invasive and metastatic urothelial carcinoma. [2019]