Atezolizumab + Chemotherapy for Bladder Cancer

Recruiting at 2 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for people with locally advanced bladder cancer. It examines the use of atezolizumab (Tecentriq), a type of immunotherapy, alongside chemotherapy drugs like platinum and etoposide to determine their effectiveness in treating cancer before surgery. The goal is to assess how well this combination eliminates cancer by the time patients undergo bladder removal surgery. People with small cell or high-grade neuroendocrine bladder cancer who are ready for surgery might be suitable for this trial. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

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.

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

Research shows that combining atezolizumab with platinum and etoposide has yielded promising results in treating small cell bladder cancer. In one instance, this treatment led to a long-term complete response in a patient with metastatic cancer, suggesting its potential effectiveness and tolerability for some patients.

However, debate continues about the safety of atezolizumab for treating urothelial carcinoma, a type of bladder cancer. Some studies suggest it can help the immune system fight cancer, but researchers are still learning about its overall safety. As this trial is in an early phase, researchers are gathering information on patient tolerance and potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Atezolizumab with chemotherapy for bladder cancer because it integrates immunotherapy with traditional chemotherapy. Atezolizumab is an immune checkpoint inhibitor, which helps the body's immune system recognize and attack cancer cells more effectively, unlike standard chemotherapy alone. This combination has the potential to enhance treatment effectiveness by not only directly attacking cancer cells with chemotherapy agents like Carboplatin, Cisplatin, and Etoposide but also by boosting the immune response against the cancer. This dual approach aims to improve outcomes, especially for those with small cell or neuroendocrine carcinoma of the bladder, by potentially increasing both the response rate and duration of response.

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

In this trial, participants will receive a combination of the drug atezolizumab with the chemotherapy drugs platinum and etoposide, followed by surgery. Research has shown that this combination may help treat small cell bladder cancer. Specifically, one case demonstrated that this treatment made the cancer undetectable for an extended period. A study using this drug combination followed by surgery showed promise for patients with localized small cell neuroendocrine bladder cancer. However, some experts still question the effectiveness and safety of atezolizumab for treating bladder cancer. Although data remains limited, these findings suggest potential benefits. ^{1 2 5 6 7}

Who Is on the Research Team?

Jean Hoffman-Censits, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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, 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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9637296/

Long-term complete response in small cell bladder ... We report the first case of metastatic SCBC where carboplatin, etoposide, and atezolizumab achieved long-term complete response.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.TPS599

Atezolizumab with platinum and etoposide chemotherapy ... Atezolizumab with platinum and etoposide chemotherapy followed by cystectomy for patients with localized small cell neuroendocrine bladder cancer.

3. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05312671?draw=2&rank=1

Atezolizumab Plus Etoposide and Platinum in Small Cell ... This is a single arm, Phase II trial involving the use of atezolizumab plus platinum and etoposide for patients with locally advanced urothelial cancer.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11983893/

Efficacy and safety of atezolizumab in the treatment ... There is still controversy regarding the safety and efficacy of atezolizumab for the treatment of urothelial carcinoma (UC).

5. urotoday.com urotoday.com/conference-highlights/astro-2024/astro-2024-bladder-cancer/155354-astro-2024-emerging-systemic-therapy-and-trials-for-small-cell-cancer-of-the-genitourinary-tract.html

Emerging Systemic Therapy and Trials for Small Cell ... Checkpoint inhibitors for small cell bladder cancer to date are limited to case reports and case series, with several treatment options and ...

6. ascopubs.org ascopubs.org/doi/10.1200/EDBK_430336

Emerging Insights in Small-Cell Carcinoma of the ... Emerging data suggest that small-cell bladder and prostate cancers transdifferentiate from a common progenitor of conventional urothelial ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03513952

Study Details | NCT03513952 | Atezolizumab and CYT107 ... Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor ...