Chemotherapy + Nivolumab for Bladder Cancer

Recruiting at 342 trial locations

Overseen By BMS Study Connect Contact Center http://www.bmsstudyconnect.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Disqualifiers: Metastatic bladder cancer, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

861 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare nivolumab plus neoadjuvant gemcitabine/cisplatin (GC) chemotherapy, followed by post-surgery continuation of immuno-oncology (IO) therapy, with neoadjuvant GC chemotherapy alone in adult participants with previously untreated muscle-invasive bladder cancer (MIBC).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination of Chemotherapy + Nivolumab for Bladder Cancer?

Research shows that the combination of gemcitabine and cisplatin is effective for treating bladder cancer, with a better balance of effectiveness and side effects compared to older treatments. Additionally, immune checkpoint inhibitors like Nivolumab have shown promise in treating bladder cancer, especially for patients who cannot use cisplatin. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs like Cisplatin and Gemcitabine safe for treating bladder cancer?

Cisplatin (also known as CDDP) can cause side effects like severe leukopenia (low white blood cell count), thrombocytopenia (low platelet count), nausea, vomiting, and nephrotoxicity (kidney damage), with some cases leading to renal failure. Gemcitabine, when used in combination with other drugs, has been generally well tolerated, though some patients experienced severe fatigue and hand-foot reactions. Overall, these treatments have shown some safety concerns, but they are often considered manageable. ^{6 7 8 9 10}

How does the drug combination of Chemotherapy + Nivolumab for Bladder Cancer differ from other treatments?

This treatment combines chemotherapy drugs cisplatin and gemcitabine, which are known for their effectiveness and better safety profile compared to older regimens, with nivolumab, an immunotherapy drug that helps the immune system attack cancer cells, offering a potentially more effective approach for advanced bladder cancer. ^{2 11 12 13 14}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults with muscle-invasive bladder cancer who haven't had previous systemic therapy, radiation, or surgery (except certain biopsies and tumor resections). They must be fit enough for surgery as assessed by their doctors and have a performance status showing they can handle daily activities with ease or minor limitations.

Inclusion Criteria

I am approved for and agree to have bladder removal surgery after initial treatment.

I am fully active or can carry out light work.

Exclusion Criteria

My cancer has spread to my lymph nodes or is metastatic bladder cancer.

I have only had TURBT or biopsies for my bladder cancer, no other treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant gemcitabine/cisplatin (GC) chemotherapy, with or without nivolumab

12 weeks

Surgery

Participants undergo surgery for muscle-invasive bladder cancer

1 week

Post-Surgery Therapy

Participants receive continued immuno-oncology therapy with nivolumab or nivolumab and BMS-986205

43 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

Treatment Details

Interventions

• Cisplatin
• Gemcitabine
• Nivolumab

Trial Overview The study compares two approaches: one group receives chemotherapy drugs gemcitabine/cisplatin alone, while the other gets these chemo drugs plus Nivolumab. After surgery to remove the bladder, some participants will continue treatment with Nivolumab or Nivolumab combined with BMS-986205.

Participant Groups

Group I: Arm B: Nivolumab + GC Chemotherapy Experimental Treatment 3 Interventions

Group II: Arm A: Gemcitabine/Cisplatin (GC) Chemotherapy Active Control 2 Interventions

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?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Ono Pharmaceutical Co. Ltd

Industry Sponsor

Trials

182

Recruited

97,100+

Shinji Takai

Ono Pharmaceutical Co. Ltd

Chief Medical Officer since 2023

MD from an unspecified institution

Gyo Sagara

Ono Pharmaceutical Co. Ltd

Chief Executive Officer since 2024

PhD in Pharmaceutical Sciences from Kyoto University

Findings from Research

The gemcitabine and cisplatin doublet regimen has shown a better efficacy-toxicity profile compared to the traditional MVAC chemotherapy for bladder cancer, making it a more suitable option for elderly patients with metastatic disease.

Ongoing phase II studies of triplet regimens combining gemcitabine, paclitaxel, and either cisplatin or carboplatin have demonstrated promising activity and improved median survival, particularly in patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of gemcitabine triplets in metastatic bladder cancer. de Wit, R., Bellmunt, J.[2022]

In a study of 11 patients with untreated metastatic bladder cancer, cis-diamminedichloroplatinum (CDDP) showed a partial response in 37.5% of patients, indicating some efficacy in this difficult-to-treat population.

While CDDP was generally tolerated, it caused moderate nausea and vomiting in some patients, and nephrotoxicity was a significant concern, leading to renal failure in 2 patients with ureteral obstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. De Lena, M., Lorusso, V., Iacobellis, U., et al.[2022]

The sequential treatment of gemcitabine and cisplatin followed by docetaxel showed a promising objective response rate of 55.2% in 38 patients with advanced urothelial carcinoma, indicating its efficacy as a first-line therapy.

The treatment was generally well tolerated, with manageable side effects; although 27% experienced severe neutropenia during the GP regimen, there were no toxic deaths reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential gemcitabine and cisplatin followed by docetaxel as first-line treatment of advanced urothelial carcinoma: a multicenter phase II study of the Hellenic Oncology Research Group. Boukovinas, I., Androulakis, N., Vamvakas, L., et al.[2022]

In a phase II study involving 27 patients with advanced transitional cell carcinoma, the sequential treatment of gemcitabine and carboplatin followed by paclitaxel resulted in an objective response rate of 40.7%, with one complete response and ten partial responses.

The treatment was generally safe, with hematologic toxicities being the most common, but the study concluded that while this sequential approach appears safer than triplet therapy, it did not significantly improve patient outcomes, indicating a need for further research with larger groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential therapy with gemcitabine and Carboplatin followed by Paclitaxel as first line treatment for advanced urothelial cancer. Kattan, JG., Boutros, CY., Farhat, FS., et al.[2021]

Gemcitabine, a newer chemotherapy agent, has shown promising activity against bladder cancer, both as a single agent and in combination with cisplatin, offering a favorable toxicity profile compared to traditional treatments.

The standard treatment for advanced bladder cancer in the US remains the M-VAC regimen, but ongoing trials are exploring the effectiveness of gemcitabine combined with other agents, which may lead to improved treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of bladder cancer. Ryan, CW., Vogelzang, NJ.[2022]

In a phase III trial with 405 patients, the gemcitabine/cisplatin (GC) regimen showed comparable effectiveness to the standard MVAC regimen for advanced bladder cancer, with similar response rates and overall survival.

The GC regimen demonstrated significantly better safety and tolerability, with much lower rates of severe side effects like mucositis and neutropenic fever, suggesting it should be preferred as the standard treatment for advanced bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in advanced bladder cancer. von der Maase, H.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Overview of gemcitabine triplets in metastatic bladder cancer. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

State-of-the-art management of metastatic disease at initial presentation or recurrence. [2022]

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

Evolving Treatment of Advanced Urothelial Cancer. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Weekly gemcitabine and cisplatin combination therapy in patients with transitional cell carcinoma of the urothelium: a phase II clinical trial. [2022]

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

Salvage therapy for recurrence of bladder cancer: do we need a uniform approach? [2014]

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

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. [2022]

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

Safety and efficacy of combination therapy with low-dose gemcitabine, paclitaxel, and sorafenib in patients with cisplatin-resistant urothelial cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Biweekly paclitaxel and gemcitabine for patients with advanced urothelial cancer ineligible for cisplatin-based regimen. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Sequential gemcitabine and cisplatin followed by docetaxel as first-line treatment of advanced urothelial carcinoma: a multicenter phase II study of the Hellenic Oncology Research Group. [2022]

10. Australia pubmed.ncbi.nlm.nih.gov

Sequential therapy with gemcitabine and Carboplatin followed by Paclitaxel as first line treatment for advanced urothelial cancer. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of bladder cancer. [2022]

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

Gemcitabine in advanced bladder cancer. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Phase II study of gemcitabine and cisplatin in patients with advanced or metastatic bladder cancer: long-term follow-up of a 3-week regimen. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Retrospective analysis of the efficacy and safety of neoadjuvant gemcitabine and cisplatin in muscle-invasive bladder cancer. [2022]