Atezolizumab + Chemotherapy for Bladder Cancer

Not currently recruiting at 9 trial locations

Overseen By Samuel Funt, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anticancer therapy, Immunosuppressants

Disqualifiers: Liver disease, CNS malignancy, Autoimmune, 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: Unknown

Duration: 15-24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well the drug atezolizumab (an immunotherapy) works with standard chemotherapy in treating bladder cancer. Researchers seek to determine if administering chemotherapy before or after atezolizumab affects cancer treatment outcomes. Participants must have bladder cancer that is locally advanced or has metastasized. This trial may suit those who have not yet received chemotherapy for their metastatic cancer and can undergo a biopsy. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 treatments like chemotherapy, immunotherapy, and some herbal therapies must be stopped before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research shows that combining atezolizumab with the chemotherapy drugs gemcitabine and cisplatin is generally well-tolerated by patients. One study found that many patients with bladder cancer responded positively to this treatment.

Previous studies have examined the safety of this combination and found that while some side effects occur, they are similar to those typically seen with these medications. Common side effects might include fatigue, nausea, or changes in blood counts, but these are often manageable.

Atezolizumab, a type of immunotherapy, has been used to treat other cancers, so its safety in humans is already known. It's important to remember that every treatment can have side effects, which can vary from person to person. However, past research provides a positive view of the safety of using atezolizumab with gemcitabine and cisplatin for bladder cancer patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments combining atezolizumab with chemotherapy for bladder cancer because they offer a fresh approach compared to standard options like surgery, radiation, and traditional chemotherapy alone. Atezolizumab is an immunotherapy drug that works by blocking the PD-L1 protein, which can help the immune system attack cancer cells more effectively. This is different from the usual chemotherapy, which directly targets and kills cancer cells but can also harm healthy cells. The combination of atezolizumab with chemotherapy might enhance the overall effectiveness by using the body's immune system alongside traditional cancer-killing methods. Additionally, this approach has the potential to optimize treatment duration and reduce side effects, making it a promising alternative for bladder cancer patients.

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

Research has shown that atezolizumab holds promise for treating urothelial cancer, including bladder cancer. It extends survival in patients with advanced cases and slows disease progression. In this trial, participants will receive different combinations of atezolizumab with the standard chemotherapy drugs gemcitabine and cisplatin. Some participants will initially receive atezolizumab alone, followed by the combination with gemcitabine and cisplatin, while others will start with gemcitabine and cisplatin before adding atezolizumab. Studies indicate that these combinations can be more effective than some other chemotherapy treatments. Early findings suggest that adding atezolizumab to gemcitabine and cisplatin offers a promising approach for treating muscle-invasive bladder cancer. ^{4 6 7 8 9}

Who Is on the Research Team?

Samuel Funt, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced bladder cancer that can't be surgically removed or has spread, who haven't had chemotherapy or immunotherapy for metastatic disease. They must have a life expectancy of at least 12 weeks, measurable disease amenable to biopsy, and agree to use effective contraception post-treatment. Excluded are those with prior transplants, heart disease class III/IV, certain recent treatments including investigational drugs and systemic steroids, known liver diseases or bone marrow disorders, active infections like HIV/Hepatitis B/C/TB, severe allergies to specific antibodies or proteins.

Inclusion Criteria

I am fully active or can carry out light work.

Estimated glomerular filtration rate (eGFR) ≥ 50 ml/min/1.73m^2

Life expectancy ≥ 12 weeks

Exclusion Criteria

I haven't had cancer treatment in the last 3 weeks.

I have not had any other cancers in the last 5 years.

I have been treated with drugs targeting PD-1 or PD-L1.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab alone or in combination with gemcitabine and cisplatin in different dosing schedules

15-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Cisplatin
• Gemcitabine

Trial Overview The trial is testing the effectiveness of Atezolizumab (an immune therapy drug) combined with Gemcitabine and Cisplatin (chemotherapy drugs) in two different sequences: one where chemotherapy is given before Atezolizumab and another where it's given after. The goal is to see which sequence works better against metastatic bladder cancer.

How Is the Trial Designed?

Group I: Atezolizumab with Gemcitabine and Cisplatin Experimental Treatment 3 Interventions

Gemcitabine and Cisplatin for 2 cycles. One treatment cycle equals 21 days. After 2 cycles of Gemcitabine and Cisplatin patient will receive combined atezolizumab and Gemcitabine and Cisplatin for 4 cycles. All 6 treatment cycles will take approximately 18 weeks. If carboplatin is substituted for cisplatin, eGFR for dosing may be calculated by institutional standard formulas, at the discretion of the treating investigator.

Group II: Atezolizumab alone with Gemcitabine and Cisplatin Experimental Treatment 3 Interventions

Atezolizumab alone for 2 cycles. One treatment cycle equals 21 days. Then patient will receive combined atezolizumab and Gemcitabine and Cisplatin for 6 cycles. All 8 treatment cycles will take approximately 24 weeks. If carboplatin is substituted for cisplatin, eGFR for dosing may be calculated by institutional standard formulas, at the discretion of the treating investigator. This cohort is NO LONGER ACCRUING patients since 5/22/2018.

Group III: Atezolizumab alone for 1 cycle prior to gemcitabine, cisplatin Experimental Treatment 3 Interventions

Atezolizumab alone for 1 cycle. One treatment cycle equals 21 days. After 1 cycle of atezolizumab the patients will receive combined atezolizumab and gemcitabine, cisplatin for 4 cycles. All 5 treatment cycles will take approximately 15 weeks. Cisplatin dose can be given on day 1 or split over days 1 and 8 at the investigator"s discretion. Once the split-dose cisplatin is used, it should be used for the remainder of the chemotherapy treatment course.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Ohio State University

Collaborator

Trials

891

Recruited

2,659,000+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

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

Targos

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

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 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]

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 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]

In a long-term follow-up of patients with metastatic urothelial carcinoma (mUC) who had previously undergone platinum-based chemotherapy, atezolizumab showed a 24-month overall survival (OS) rate of 23%, compared to 13% for those receiving chemotherapy, indicating a potential for durable remission.

Patients treated with atezolizumab experienced fewer severe treatment-related adverse events (43% for chemotherapy vs. 22% for atezolizumab), suggesting a better safety profile, although atezolizumab was associated with more mild adverse events of special interest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab Versus Chemotherapy in Patients with Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: A Long-term Overall Survival and Safety Update from the Phase 3 IMvigor211 Clinical Trial. van der Heijden, MS., Loriot, Y., Durán, I., et al.[2022]

Citations

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A Phase II Study of Atezolizumab in Combination With ... The purpose of this study is to test the safety of the study drug, atezolizumab, when combined with the standard chemotherapy drugs, gemcitabine and cisplatin ( ...

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versus carboplatin-based chemotherapy plus atezolizumab ... The IMvigor130 trial reveals more favorable effects with atezolizumab combined with gemcitabine and cisplatin (GemCis) versus gemcitabine and carboplatin ( ...