Atezolizumab + Chemotherapy for Bladder Cancer

Recruiting at 1 trial location

Overseen By Deborah Schwartz, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Antibiotics, Immunosuppressants, Immunostimulants, others

Disqualifiers: Metastatic disease, Active tuberculosis, 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

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

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

63 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, certain medications like systemic immunosuppressive drugs and some antibiotics should not be taken close to the start of the study treatment. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug Atezolizumab for bladder cancer?

Atezolizumab has shown effectiveness in treating advanced bladder cancer, especially in patients who cannot receive cisplatin chemotherapy. Studies have reported that it leads to durable tumor responses, with a 15% response rate in patients whose cancer progressed after platinum-based chemotherapy and a 24% response rate in those who were chemotherapy-naïve and cisplatin ineligible. Additionally, it has a favorable safety profile compared to traditional chemotherapy. ^{1 2 3 4 5}

Is the combination of Atezolizumab and chemotherapy safe for treating bladder cancer?

Atezolizumab, when used for advanced bladder cancer, has shown a favorable safety profile with manageable side effects in clinical trials. Most treatment-related side effects were mild, with a small percentage of patients experiencing more severe reactions. ^{1 2 3 4 6}

What makes the drug Atezolizumab unique for bladder cancer treatment?

Atezolizumab is unique because it is a monoclonal antibody that blocks PD-L1, enhancing the immune system's ability to attack bladder cancer cells. It is particularly beneficial for patients who cannot tolerate cisplatin chemotherapy, offering a more effective alternative with a favorable safety profile. ^{1 2 3 4 7}

What is the purpose of this trial?

This is a single arm, Phase II trial involving the use of atezolizumab plus platinum and etoposide for patients with locally advanced urothelial cancer. The primary goal of this trial is to assess the pathologic complete response rate at cystectomy in patients after being treated with a combination therapy of atezolizumab, platinum, and etoposide.

Research Team

Jean Hoffman-Censits, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults with small cell bladder cancer who haven't had prior systemic treatment for it. They must be fit enough for chemo, immunotherapy, and surgery, have a performance status of 0 or 1, and agree to use birth control. A tumor sample is needed before joining. People with recent other cancers, severe allergies to drugs in the study, active infections like HIV or hepatitis B, or certain heart conditions can't join.

Inclusion Criteria

Patients who give a written informed consent obtained according to local guidelines

My bladder cancer is confirmed and aggressive, with or without urothelial cancer.

You must have a negative HIV test, unless there are specific reasons why this doesn't apply to you.

Exclusion Criteria

I have received treatment for small-cell bladder cancer before.

I have had a previous transplant of stem cells or an organ.

I am currently on medication for hepatitis B.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Atezolizumab with Platinum and Etoposide chemotherapy for 4 cycles, each cycle lasting 21 days

12 weeks

4 visits (in-person)

Surgery

Participants undergo cystectomy to surgically resect their cancer

1 week

1 visit (in-person)

Maintenance

Atezolizumab maintenance therapy every 21 days until unacceptable toxicity or loss of clinical benefit, up to 1 year

up to 1 year

Follow-up

Participants are monitored for safety, effectiveness, and disease recurrence after treatment

up to 5 years

Treatment Details

Interventions

• Atezolizumab
• Carboplatin
• Cisplatin
• Cystectomy
• Etoposide

Trial Overview The trial tests atezolizumab combined with platinum (carboplatin or cisplatin) and etoposide chemotherapy in patients undergoing cystectomy (bladder removal surgery). It's a Phase II study focusing on how many patients achieve no sign of cancer after this combination therapy.

Participant Groups

Group I: Atezolizumab with Platinum and Etoposide, followed by cystectomy. Experimental Treatment 5 Interventions

The study population will include male and female patients over the age of 18 with invasive (cT1-cT4) small cell / neuroendocrine carcinoma of the bladder (MIBC), with or without urothelial cancer component, who are eligible for platinum based chemotherapy and immunotherapy. All patients will be fit to undergo surgical resection of their cancer by cystectomy. Patients with resectable N1 disease within the true pelvis are eligible. Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg Day 1 of every 21 day cycle with chemotherapy x 4 cycles. Following cystectomy, Atezolizumab maintenance Q 21 days will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status (e.g., symptomatic deterioration such as pain secondary to disease), or up to 1 year (e.g., 16 cycles).

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

Atezolizumab, an anti-PD-L1 monoclonal antibody, has shown durable responses in treating locally advanced and metastatic urothelial cancer, especially in patients who have failed platinum-based chemotherapy or are ineligible for cisplatin.

The treatment with atezolizumab has a more favorable toxicity profile compared to traditional cytotoxic chemotherapy, making it a promising option for patients with advanced bladder cancer, although further research is needed to identify additional predictive markers for response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. Crist, M., Balar, A.[2019]

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]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab, a monoclonal antibody targeting PD-L1, showed a 23% response rate and a median overall survival of 15.9 months in 119 patients with metastatic urothelial cancer who were unfit for cisplatin, indicating its efficacy as a front-line treatment.

In patients whose tumors progressed after first-line chemotherapy, atezolizumab had a 15% response rate and a median overall survival of 7.9 months, with better outcomes (26% response rate) in those with high PD-L1 expression, demonstrating its potential effectiveness based on biomarker status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. Bernard-Tessier, A., Bonnet, C., Lavaud, P., et al.[2019]

Atezolizumab, a PD-L1 inhibitor, has shown effectiveness as a first-line treatment for advanced bladder cancer in patients who cannot receive standard cisplatin chemotherapy, according to a phase II study.

Nearly 25% of the patients in the study experienced durable responses to atezolizumab, highlighting its potential as a viable treatment option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Atezolizumab Effective in Bladder Cancer. [2019]

In a study of 115 patients with metastatic urothelial carcinoma treated with atezolizumab (ATZ) after failing first-line chemotherapy, the objective response rate was 28.7%, indicating that ATZ is effective in this patient population.

The treatment was well tolerated, with 98% of patients experiencing adverse events, but only 21.2% had severe (grade 3-4) treatment-related adverse events, suggesting a manageable safety profile similar to previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. Tural, D., Ölmez, ÖF., Sümbül, AT., et al.[2022]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. [2019]

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

Nod for Atezolizumab in Advanced Bladder Cancer. [2018]

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019]

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

First-Line Atezolizumab Effective in Bladder Cancer. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]