Chemotherapy Combinations with Nivolumab for Bladder Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two different combinations of chemotherapy drugs with nivolumab, a type of immunotherapy, for people with advanced bladder cancer who can't use the standard cisplatin treatment. Researchers aim to determine how effectively these combinations shrink tumors or control the cancer. The trial seeks participants with advanced bladder cancer that is inoperable and untreated with chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that most people can handle the combination of nivolumab with chemotherapy drugs like gemcitabine and carboplatin. In a previous study, 74% of patients completed their treatment with this combination, indicating that side effects usually don't lead to early discontinuation.

The FDA has approved nivolumab for use with a similar chemotherapy drug, cisplatin, for certain cancer treatments, demonstrating strong evidence of its safety.

For the combination of gemcitabine, oxaliplatin, and nivolumab, less specific information is available. However, nivolumab is generally known to cause serious side effects, such as urinary tract infections and kidney issues, in a small number of patients (about 2-5%).

This study is a Phase 2 trial, meaning researchers have some early evidence of the treatments' safety, but they continue to monitor side effects and patient tolerance closely. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for bladder cancer because they combine chemotherapy with nivolumab, an immunotherapy drug that helps the body's immune system attack cancer cells more effectively. Unlike traditional treatments, which typically rely on single-agent chemotherapy, these combinations aim to enhance the overall response by adding nivolumab. In Arm A, gemcitabine and carboplatin are paired with nivolumab, potentially offering a more robust attack on cancer cells. Arm B swaps carboplatin for oxaliplatin, which might be more effective or better tolerated for some patients. By integrating nivolumab into these combinations, there's hope for improved outcomes compared to standard chemotherapy alone.

What evidence suggests that this trial's treatments could be effective for metastatic urothelial cancer?

This trial will compare two chemotherapy combinations with nivolumab for bladder cancer. Studies have shown that using nivolumab with gemcitabine and carboplatin, which participants in Arm A may receive, can lead to better outcomes for patients with advanced bladder cancer. Specifically, patients treated with this combination lived an average of 12.8 months, and research demonstrated it can significantly slow cancer growth.

Participants in Arm B will receive gemcitabine, oxaliplatin, and nivolumab. Although less information is available about this specific combination, nivolumab has shown promise in other studies when used with similar chemotherapy drugs, suggesting it could help slow the disease. Both combinations aim to improve treatment for those who cannot receive cisplatin, a common chemotherapy drug. ^{1 2 3 6 7}

Who Is on the Research Team?

Matthew Galsky, M.D.

Principal Investigator

Icahn School of Medicine at Mount Sinai; Tisch Cancer Institute

Are You a Good Fit for This Trial?

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

I do not have any serious or uncontrolled health issues.

Known left ventricular ejection fraction (LVEF) < 40%

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2309863

Nivolumab plus Gemcitabine–Cisplatin in Advanced ... Combination therapy with nivolumab plus gemcitabine–cisplatin resulted in significantly better outcomes in patients with previously untreated advanced ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11543197/

FDA approves nivolumab in combination with cisplatin and ... Median time to progression was found to be 8.3 months for Gemcitabine-cisplatin and 7.7 months for Gemcitabine-carboplatin. Median survival rate was 12.8 months ...

3. onclive.com onclive.com/view/enhanced-bladder-cancer-outcomes-stem-from-individualized-first-line-regimens

Enhanced Bladder Cancer Outcomes Stem From ... The data [in this population] look strong for cisplatin plus gemcitabine and nivolumab, as well as for carboplatin or cisplatin plus gemcitabine ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03451331?term=NCT00002854%20NCT00003597%20NCT00113438%20NCT00147225%20NCT00193583%20NCT00268905%20NCT00277069%20NCT00581971%20NCT00752011%20NCT00881166%20NCT00927589%20NCT01110603%20NCT01178112%20NCT01187199%20NCT01192165%20NCT01204996%20NCT01287520%20NCT01301716%20NCT01376310%20NCT01497470%20NCT01542047%20NCT01604863%20NCT01633970%20NCT01636622%20NCT01653470%20NCT01688791%20NCT02018861%20NCT02071537%20NCT02240017%20NCT02383212%20NCT02813135%20NCT02941523%20NCT03451331%20NCT03498521%20NCT03547973%20NCT05229497%20NCT05298592&rank=5

Study Details | NCT03451331 | Gemcitabine + Carboplatin ... This is a randomized phase 2 trial of gemcitabine + carboplatin + nivolumab or gemcitabine + oxaliplatin + nivolumab for the treatment of cisplatin-ineligible ...

5. opdivohcp.com opdivohcp.com/efficacy/uc/first-line

OPDIVO® (nivolumab) Efficacy Data for 1L Treatment of ... OPDIVO + chemotherapy has a finite duration of treatment, with up to 6 cycles of OPDIVO + chemotherapy followed by OPDIVO monotherapy for up to 2 years.

6. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-combination-cisplatin-and-gemcitabine-unresectable-or-metastatic-urothelial

FDA approves nivolumab in combination with cisplatin and ... Statistically significant benefits in both OS and PFS were demonstrated for nivolumab in combination with cisplatin and gemcitabine followed by ...

7. news.bms.com news.bms.com/news/details/2024/Bristol-Myers-Squibb-Receives-European-Commission-Approval-for-Opdivo-nivolumab-in-Combination-with-Cisplatin-and-Gemcitabine-for-the-First-Line-Treatment-of-Adult-Patients-with-Unresectable-or-Metastatic-Urothelial-Carcinoma/default.aspx

Approval based on results from CheckMate OS (overall survival; primary endpoint): Opdivo in combination with cisplatin and gemcitabine reduced the risk of death in patients by 22%, ...