Immunochemotherapy for Bladder Cancer

Recruiting at 3 trial locations

Overseen By Daniel Geynisman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Must not be taking: Antiretrovirals, Corticosteroids, Immunosuppressants, others

Disqualifiers: Small cell histology, Recent chemotherapy, Active malignancy, 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)

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

81 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of chemotherapy and immune therapy for patients with muscle invasive bladder cancer. It aims to help these patients keep their bladders and improve their quality of life by effectively targeting and killing cancer cells while boosting the immune system.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug AMVAC + Nivolumab for bladder cancer?

Nivolumab, a part of the AMVAC + Nivolumab treatment, has been approved by the FDA for advanced bladder cancer after showing effectiveness in patients whose disease progressed on platinum chemotherapy. This approval is based on its ability to target and block a protein that helps cancer cells evade the immune system, thereby promoting antitumor activity. ^{1 2 3 4 5}

Is the combination of AMVAC + Nivolumab generally safe for humans?

Nivolumab, used in combination with other treatments for bladder cancer, is generally well tolerated, but some common side effects include fatigue, low blood cell counts, muscle pain, decreased appetite, and nausea. It has been approved for use in bladder cancer after other treatments have failed, indicating a recognized safety profile. ^{1 3 6 7 8}

How is the drug AMVAC + Nivolumab different from other bladder cancer treatments?

AMVAC + Nivolumab combines a dose-intense chemotherapy regimen (AMVAC) with an immunotherapy drug (Nivolumab) that targets the PD-1 pathway, potentially enhancing the immune system's ability to fight cancer. This combination aims to provide a more effective treatment by leveraging both chemotherapy and immunotherapy, which is different from traditional treatments that typically use only one approach. ^{1 7 9 10 11}

Research Team

Pooja Ghatalia, MD

Principal Investigator

Fox Chase Cancer Center

Eligibility Criteria

This trial is for adults with muscle invasive bladder cancer (MIBC) without prior chemotherapy or radiation for urothelial carcinoma, no autoimmune diseases, and not on significant immunosuppressive medications. Participants must have normal organ function, no evidence of metastasis or lymph node positive disease unless biopsy-proven negative, and a good performance status.

Inclusion Criteria

There is evidence that the cancer has invaded the muscle layer of the organ.

Your cancer is at a specific stage called T2 or T3 and has not spread to nearby lymph nodes or other parts of the body.

Male or female patients ≥18 years

Exclusion Criteria

You have had chemotherapy or radiation for urothelial carcinoma within the past year, or you have had immunotherapy for non-muscle invasive bladder cancer.

You have a type of cancer called small cell histology.

You have a history of certain autoimmune diseases like rheumatoid arthritis or lupus.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant nivolumab with AMVAC for muscle invasive bladder cancer

12 weeks

3 cycles of treatment

Active Surveillance

Patients with complete clinical response undergo active surveillance to preserve their bladders

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• AMVAC + Nivolumab

Trial Overview The study tests neoadjuvant accelerated methotrexate/vinblastine/adriamycin/cisplatin (AMVAC) combined with nivolumab in MIBC patients. Those responding well may preserve their bladders and enter active surveillance instead of undergoing radical surgery.

Participant Groups

Group I: AMVAC + nivolumab Experimental Treatment 1 Intervention

This will be a single-arm, open-label, multicenter phase 2 study of neoadjuvant nivolumab with AMVAC. Approximately 70 evaluable patients will be enrolled into this study. Eligible patients will be those with diagnosis of muscle invasive urothelial carcinoma of the bladder who are cT2 or cT3 but not clinical N1 at diagnosis. Clinical stage is confirmed by transurethral resection of bladder tumor (TURBT#1).

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

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]

Nivolumab has received accelerated approval from the FDA for treating patients with locally advanced or metastatic urothelial carcinoma who have experienced disease progression after platinum chemotherapy.

This approval marks the second PD-1-targeting therapy approved for bladder cancer within a year, highlighting the growing options for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Gets FDA Nod for Bladder Cancer. [2018]

Recent advancements in the treatment of advanced-stage urothelial carcinoma, a common type of bladder cancer, include the FDA approval of several immune checkpoint inhibitors such as nivolumab, pembrolizumab, and atezolizumab.

Despite these promising new therapies, clinicians face challenges in selecting the most effective treatment options for patients, particularly in determining the best first-line or second-line therapies to improve overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Changing Treatment Landscape for Metastatic Urothelial Carcinoma. Flaig, TW.[2019]

In a phase II trial involving 51 patients with muscle-invasive bladder cancer, the combination of nivolumab and gemcitabine/cisplatin (N+GC) was well tolerated and resulted in a clinical complete response in 59% of patients, indicating its potential effectiveness as a neoadjuvant treatment.

The treatment led to a pathologic complete response in 24% of patients overall and 35% among those who underwent radical cystectomy, suggesting that N+GC can achieve significant tumor reduction before surgery, regardless of the patients' PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder. Kim, H., Jeong, BC., Hong, J., et al.[2023]

In a study of 1,747 patients with advanced urothelial cancer, those who responded to anti-PD-1/L1 antibody treatment were more likely to experience adverse events of special interest (AESIs) and immune-mediated adverse events (imAEs), with 64% of responders reporting related AESIs compared to 34% of non-responders.

Patients with related AESIs had significantly improved overall survival, with a hazard ratio of 0.45, indicating that experiencing these adverse events may be associated with better treatment outcomes, regardless of the duration of exposure to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the Association Between Adverse Events and Outcome in Patients Receiving a Programmed Death Protein 1 or Programmed Death Ligand 1 Antibody. Maher, VE., Fernandes, LL., Weinstock, C., et al.[2020]

References

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

[Immunotherapy for Bladder Cancer]. [2019]

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

Evolving Treatment of Advanced Urothelial Cancer. [2018]

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

Nivolumab Gets FDA Nod for Bladder Cancer. [2018]

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

The Changing Treatment Landscape for Metastatic Urothelial Carcinoma. [2019]

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

Immunotherapy in urothelial cancer, part 1: T-cell checkpoint inhibition in advanced or metastatic disease. [2020]

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

Preexisting Autoantibodies and Immune Related Adverse Events in Metastatic Urothelial Carcinoma Patients Treated by Pembrolizumab. [2022]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder. [2023]

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

Analysis of the Association Between Adverse Events and Outcome in Patients Receiving a Programmed Death Protein 1 or Programmed Death Ligand 1 Antibody. [2020]

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

Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Accelerated MVAC chemotherapy in patients with advanced bladder cancer previously treated with a platinum-gemcitabine regimen. [2022]

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

Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle-invasive transitional cell carcinoma of the bladder. [2022]