Chemotherapy Combinations with Nivolumab for Bladder Cancer

Recruiting at 5 trial locations

Overseen By Matthew Galsky, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Matthew Galsky

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Active infection, Autoimmune disease, Cardiovascular 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: 18 weeks

49 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you must stop them at least 14 days before starting the study drugs.

What data supports the effectiveness of the drug combination including Nivolumab for bladder cancer?

Nivolumab, a type of immunotherapy, has shown promise in treating bladder cancer, especially for patients who cannot tolerate traditional chemotherapy. Studies have found that drugs like Nivolumab can improve survival rates in patients with advanced bladder cancer, particularly when other treatments are not suitable. ^{1 2 3 4 5}

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

Nivolumab and other similar immunotherapy drugs are generally well tolerated in bladder cancer patients, with common side effects including tiredness, low blood cell counts, muscle pain, reduced appetite, and nausea. Carboplatin, used in combination with other treatments, is also well tolerated, with a small percentage of patients experiencing severe bladder-related side effects. ^{1 6 7 8 9}

How is the drug combination of Carboplatin, Nivolumab, and Oxaliplatin unique for treating bladder cancer?

This drug combination is unique because it integrates immunotherapy with chemotherapy, using Nivolumab, a checkpoint inhibitor that enhances the immune system's ability to fight cancer, alongside Carboplatin and Oxaliplatin, which are chemotherapy drugs. This approach is particularly beneficial for patients who cannot tolerate cisplatin, the standard chemotherapy, and offers a novel option for those with advanced bladder cancer. ^{1 2 7 10 11}

What is the purpose of this trial?

This trial is testing two combinations of drugs for patients with advanced bladder cancer who can't use a common chemotherapy drug. The treatment includes drugs to kill cancer cells and another to help the immune system fight the cancer.

Research Team

Matthew Galsky, M.D.

Principal Investigator

Icahn School of Medicine at Mount Sinai; Tisch Cancer Institute

Eligibility Criteria

Adults with advanced bladder cancer that can't be treated with cisplatin and haven't had chemotherapy for it. They must have a certain level of kidney, liver, and blood cell function, not be pregnant or breastfeeding, use contraception if needed, and have no serious health issues or recent other cancers. People who've had immune system treatments or suffer from autoimmune diseases (except mild forms), severe heart problems, transplants, active infections requiring treatment, HIV/AIDS or hepatitis are excluded.

Inclusion Criteria

I have not had chemotherapy for my advanced urinary cancer.

My cancer is advanced bladder cancer confirmed by a biopsy.

Able to comply with the study protocol, in the investigator's judgment

Exclusion Criteria

Known positive result for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus

Known left ventricular ejection fraction (LVEF) < 40%

I do not have any serious or uncontrolled health issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 6 cycles of combination therapy with gemcitabine, carboplatin or oxaliplatin, and nivolumab

18 weeks

Maintenance

Participants with stable disease may continue with single-agent nivolumab for up to 12 cycles

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Carboplatin
• Nivolumab
• Oxaliplatin

Trial Overview This phase 2 trial is testing two combinations: Gemcitabine + Carboplatin + Nivolumab versus Gemcitabine + Oxaliplatin + Nivolumab in patients who cannot receive cisplatin for their metastatic urothelial cancer. Participants will be randomly assigned to one of these treatment groups considering their lymph node status.

Participant Groups

Group I: Arm B Experimental Treatment 3 Interventions

Gemcitabine plus oxaliplatin plus nivolumab

Group II: Arm A Experimental Treatment 3 Interventions

Gemcitabine plus carboplatin plus nivolumab

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Matthew Galsky

Lead Sponsor

Trials

12

Recruited

470+

Bristol-Myers Squibb

Industry 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

Hoosier Cancer Research Network

Collaborator

Trials

69

Recruited

3,800+

Findings from Research

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]

In a study of 107 patients with locally advanced urothelial carcinoma, combination immune checkpoint inhibition (cICI) showed superior progression-free and overall survival compared to neoadjuvant platinum-based chemotherapy (NAIC).

Patients receiving cICI had a higher rate of complete pathological response (46%) compared to those treated with NAIC (22%), suggesting that cICI may be a more effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival after neoadjuvant/induction combination immunotherapy vs combination platinum-based chemotherapy for locally advanced (Stage III) urothelial cancer. Einerhand, SMH., van Dijk, N., van Dorp, J., 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]

In a review of 8 studies involving 1,666 patients with platinum-resistant urothelial cancer, anti-PD-1 therapy showed a higher objective response rate (22%) compared to anti-PD-L1 therapy (15%), indicating better antitumor activity for anti-PD-1.

Both anti-PD-1 and anti-PD-L1 therapies had comparable safety profiles and survival outcomes, with similar rates of treatment-related adverse events and overall survival at 12 months (43% for anti-PD-1 vs. 42% for anti-PD-L1).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Activity of Programmed Cell Death 1 Versus Programmed Cell Death Ligand 1 Inhibitors for Platinum-Resistant Urothelial Cancer: A Meta-Analysis of Published Clinical Trials. Li, Z., Li, X., Lam, W., et al.[2022]

Nivolumab, a PD-1 blocking monoclonal antibody, shows effectiveness in treating metastatic urothelial carcinoma, potentially offering better survival rates compared to traditional cisplatin-based chemotherapy, which typically extends survival by only a few months.

While nivolumab has manageable toxicity, its response rate after first-line chemotherapy is under 30%, and further research is needed to identify which patients will benefit most from this treatment, especially given the high costs involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for the treatment of bladder cancer. Hakenberg, OW.[2021]

References

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

[Immunotherapy for Bladder Cancer]. [2019]

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

Integration of Immunotherapy Into the Treatment of Advanced Urothelial Carcinoma. [2021]

3. Hungary pubmed.ncbi.nlm.nih.gov

[Immunotherapy in advanced urothelial cancer]. [2021]

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

Survival after neoadjuvant/induction combination immunotherapy vs combination platinum-based chemotherapy for locally advanced (Stage III) urothelial cancer. [2022]

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

Perioperative Immunotherapy in Muscle-Invasive Bladder Cancer and Upper Tract Urothelial Carcinoma. [2018]

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

An Effective and Well Tolerated Strategy of Bladder Preservation Therapy in Cisplatin-Ineligible Patients With Muscle-Invasive Bladder Cancer. [2022]

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

Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. [2022]

8. Australia pubmed.ncbi.nlm.nih.gov

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Activity of Programmed Cell Death 1 Versus Programmed Cell Death Ligand 1 Inhibitors for Platinum-Resistant Urothelial Cancer: A Meta-Analysis of Published Clinical Trials. [2022]

10. Hungary pubmed.ncbi.nlm.nih.gov

[New aspects of chemotherapy and indications for maintenance immunotherapy in urothelial cancers]. [2021]

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

Nivolumab for the treatment of bladder cancer. [2021]