Immunochemotherapy for Bladder Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for muscle invasive bladder cancer (MIBC) to determine if patients can retain their bladders and transition to active monitoring after a positive response. The treatment combines chemotherapy drugs (AMVAC) with nivolumab, an immune therapy, before surgery to shrink tumors. Suitable candidates have bladder cancer that invades the muscle layer but has not spread to lymph nodes or other parts of the body. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that AMVAC + nivolumab is likely to be safe for humans?

Research has shown that combining AMVAC and nivolumab may effectively treat bladder cancer. AMVAC, a mix of chemotherapy drugs, often works well and usually causes fewer side effects than older treatments. Some side effects, such as fatigue and low blood counts, can occur but are generally manageable.

Nivolumab, a type of immunotherapy, is already approved for use after chemotherapy in bladder cancer. Most people tolerate it well, though some may experience fatigue or low blood pressure. Overall, studies suggest these treatments are safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Researchers are excited about the combination of AMVAC and nivolumab for bladder cancer because it uniquely combines chemotherapy with immunotherapy. Unlike standard treatments like surgery or chemotherapy alone, this approach uses nivolumab, an immune checkpoint inhibitor, to boost the body's immune response against cancer cells. Additionally, AMVAC is a chemotherapy regimen designed to be more effective against muscle-invasive bladder cancer. This combination has the potential to enhance the overall treatment effectiveness by attacking the cancer on multiple fronts, offering new hope for patients with advanced stages of the disease.

What evidence suggests that AMVAC + Nivolumab might be an effective treatment for muscle invasive bladder cancer?

Research has shown that combining AMVAC (a mix of chemotherapy drugs) with nivolumab (a type of immune therapy) may help treat muscle-invasive bladder cancer (MIBC). In earlier studies, nivolumab helped patients with high-risk MIBC live longer without cancer returning, improving the duration of cancer-free survival. The FDA has already approved nivolumab for treating advanced bladder cancer, indicating its effectiveness in similar cases. This trial will evaluate the combination of AMVAC and nivolumab, with early results suggesting that this combination could enhance these benefits, possibly helping some patients avoid bladder removal. This treatment boosts the immune system to fight cancer cells more effectively. ^{1 2 3 5 6}

Who Is on the Research Team?

Pooja Ghatalia, MD

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

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.

Negative pregnancy test in women of child bearing potential within 24 hours of study registration. If the pregnancy test is positive, the patient must not receive protocol treatment and must not be enrolled in the study

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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With extended 3 year median follow-up, continued improvements in disease free survival were seen with nivolumab versus placebo in the primary ...

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Immunochemotherapy 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 ...

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Neoadjuvant accelerated MVAC (AMVAC) in patients with ...

Compared with standard MVAC, AMVAC yielded higher response rates with less toxicity in the metastatic setting. Methods: Pts with MIBC, cT2-T4a, ...