Combination Therapy for Bladder Cancer

(NeoSTOP-IT Trial)

Overseen By Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Columbia University

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Upper tract carcinoma, Autoimmune, Transplant, 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: 21

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like systemic steroids or investigational agents within 4 weeks of starting the trial.

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

Research shows that combining gemcitabine with cisplatin is effective for treating advanced bladder cancer, with response rates up to 66% and good tolerability. Additionally, cisplatin-based regimens have been a standard treatment, improving survival rates compared to using cisplatin alone. ^{1 2 3 4 5}

What safety data exists for the combination therapy involving Cemiplimab, Cisplatin, Fianlimab, and Gemcitabine?

Studies have shown that gemcitabine and cisplatin, when used together, have been evaluated for their safety in treating bladder cancer, with a focus on managing toxicity (side effects). These treatments have been used in various combinations and have been generally considered safe, though they can cause side effects that need to be monitored. ^{6 7 8 9 10}

What makes the combination therapy for bladder cancer unique?

This combination therapy for bladder cancer is unique because it includes cemiplimab and fianlimab, which are newer immunotherapy drugs that help the immune system fight cancer, alongside the more traditional chemotherapy drugs cisplatin and gemcitabine. This approach aims to enhance the effectiveness of treatment by combining immune system activation with direct cancer cell killing. ^{2 5 11 12 13}

What is the purpose of this trial?

The goal of this clinical trial is to learn if gemcitabine/cisplatin plus cemiplimab with or without fianlimab works to treat bladder cancer in adults. The main question it aims to answer is: Can gemcitabine, cisplatin, and cemiplimab with or without fianlimab treat bladder cancer? Participants will be randomly selected (like the loss of a coin) to treatment with gemcitabine, cisplatin, cemiplimab, and fianlimab or gemcitabine, cisplatin, and cemiplimab. Participants will: * Undergo transurethral resection of bladder tumor (TURBT) followed by the start of treatment, receive 4 cycles of treatment (21 day cycles) * After 4 cycles of treatment, patients will undergo repeat maximal TURBT with imaging * Participants with a complete response will continue maintenance cemiplimab or cemiplimab/fianlimab for 13 more cycles with imaging every 3 months * Participants without a complete clinical response will undergo cystectomy (bladder surgery).

Research Team

Alexander Z Wei, MD

Principal Investigator

Columbia University

Eligibility Criteria

Adults with localized muscle-invasive bladder cancer who can undergo tumor removal and chemotherapy. Participants must be able to receive cisplatin, have no prior treatments for their condition, and not have any autoimmune diseases or conditions that could interfere with the study.

Inclusion Criteria

I am eligible to receive cisplatin treatment.

Life expectancy > 12 months

My bladder cancer is invasive but hasn't spread beyond my bladder.

Exclusion Criteria

I have had radiation therapy for bladder cancer before.

I am currently being treated for an infection.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive 4 cycles of gemcitabine, cisplatin, and cemiplimab with or without fianlimab, followed by TURBT and imaging

12 weeks

8 visits (in-person)

Recovery

Participants have a recovery period between neoadjuvant treatment and cystoscopy/TURBT

4 weeks

Adjuvant Treatment

Participants with a complete response continue maintenance cemiplimab or cemiplimab/fianlimab for 13 more cycles with imaging every 3 months

39 weeks

13 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cemiplimab
• Cisplatin
• Fianlimab
• Gemcitabine

Trial Overview The trial is testing if adding cemiplimab (an immune therapy) to standard chemo (gemcitabine/cisplatin) improves treatment outcomes in bladder cancer, with some patients also receiving fianlimab. It's a randomized study where participants are chosen by chance for different treatment combinations.

Participant Groups

Group I: Group 2: Gemcitabine/Cisplatin/Cemiplimab/Fianlimab Experimental Treatment 4 Interventions

* Gemcitabine 1000 mg/m2 IV (days 1 and 8 of 21 day cycle for 4 cycles) * Cisplatin 70 mg/m2 IV (day 1 of 21 day cycle for 4 cycles) or renally-dosed split-dose cisplatin 35 m/m2 IV (day 1 and 8 of 21 day cycle for 4 cycles ) * Cemiplimab (REGN 2810) 350mg IV every 3 weeks (4 cycles) * Fianlimab (REGN3767) 1600mg IV every 3 weeks (4 cycles)

Group II: Group 1: Gemcitabine/Cisplatin/Cemiplimab Experimental Treatment 3 Interventions

* Gemcitabine 1000 mg/m\^2 IV (days 1 and 8 of 21 day for 4 cycles) * Cisplatin 70 mg/m\^2 IV (day 1 of 21 day cycle for 4 cycles) or renally-dosed split-dose -cisplatin 35 m/m\^2 IV (day 1 and 8 of 21 day cycle for 4 cycles) * Cemiplimab (REGN 2810) 350 mg IV every 3 weeks (17 cycles)

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

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

Cisplatin-based regimens, particularly the M-VAC combination therapy, significantly improve complete response rates and overall survival in patients with advanced and metastatic bladder cancer compared to single-agent cisplatin.

For patients ineligible for cisplatin due to health issues, alternative therapies like paclitaxel, gemcitabine, and carboplatin have shown benefits, while new targeted therapies require further research to establish their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapeutic and targeted biological agents for metastatic bladder cancer: a comprehensive review. Sio, TT., Ko, J., Gudena, VK., et al.[2014]

The gemcitabine and cisplatin (CG) combination has emerged as the new standard of care for metastatic bladder carcinoma, showing similar effectiveness to the previous standard M-VAC regimen but with less toxicity.

Novel treatments like pemetrexed and vinflunine are showing promise in clinical trials, with pemetrexed demonstrating a 28% response rate and vinflunine providing an 18% response rate in pretreated patients, indicating potential for improved outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of metastatic bladder carcinoma. Iaffaioli, RV., Milano, A., Caponigro, F.[2020]

The combination of gemcitabine and carboplatin shows a promising overall response rate of 60% in treating transitional cell carcinoma of the bladder, making it a potential alternative for patients who cannot tolerate cisplatin due to renal impairment or other comorbidities.

Given the high chemosensitivity of transitional cell carcinoma, this new treatment combination warrants further investigation in future phase III trials to confirm its efficacy and safety in a broader patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine/carboplatin in advanced urothelial cancer. Carles, J., Nogué, M.[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]

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]

Atezolizumab has been approved by the FDA as a treatment for advanced bladder cancer, specifically for patients who cannot receive cisplatin chemotherapy.

This approval provides a potentially more effective treatment option compared to carboplatin-based chemotherapy, particularly for frail and elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nod for Atezolizumab in Advanced Bladder Cancer. [2018]

The combination of paclitaxel, cisplatin, and gemcitabine demonstrated a high overall response rate of 77.6% in 61 patients with advanced transitional-cell carcinoma, indicating strong antitumor activity.

The recommended doses for further studies were established as 80 mg/m² of paclitaxel and 1,000 mg/m² of gemcitabine, with manageable toxicity, although significant side effects like grade 3 neutropenia were observed in 55% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I-II study of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma of the urothelium. Spanish Oncology Genitourinary Group. Bellmunt, J., Guillem, V., Paz-Ares, L., et al.[2022]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Chemotherapeutic and targeted biological agents for metastatic bladder cancer: a comprehensive review. [2014]

2. England pubmed.ncbi.nlm.nih.gov

Therapy of metastatic bladder carcinoma. [2020]

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

Gemcitabine in bladder cancer. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

New drugs and new approaches for the treatment of metastatic urothelial cancer. [2022]

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

Gemcitabine/carboplatin in advanced urothelial cancer. [2022]

6. 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]

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

Phase Ib/II trial of gemcitabine, cisplatin, and lenalidomide as first-line therapy in patients with metastatic urothelial carcinoma. [2022]

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

Neoadjuvant Gemcitabine-Cisplatin Plus Radical Cystectomy-Pelvic Lymph Node Dissection for Muscle-invasive Bladder Cancer: A 12-year Experience. [2022]

9. 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]

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

Nod for Atezolizumab in Advanced Bladder Cancer. [2018]

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

Phase I-II study of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma of the urothelium. Spanish Oncology Genitourinary Group. [2022]

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

A Single-arm Phase II Trial of Neoadjuvant Cabazitaxel and Cisplatin Chemotherapy for Muscle-Invasive Transitional Cell Carcinoma of the Urinary Bladder. [2021]

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

Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC Intergroup Study 30987. [2022]