Chemoradiotherapy + Atezolizumab for Bladder Cancer

Not currently recruiting at 445 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Small cell carcinoma, Prior chemotherapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 3

Duration: 7-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding atezolizumab, an immunotherapy drug, to the standard chemotherapy and radiation regimen is more effective for treating muscle-invasive bladder cancer than chemotherapy and radiation alone. Chemotherapy and radiation aim to kill cancer cells, while atezolizumab may enhance the immune system's ability to fight cancer. The trial includes two groups: one receiving only chemotherapy and radiation, and the other receiving chemotherapy, radiation, plus atezolizumab. Individuals diagnosed with muscle-invasive bladder cancer who have not previously received chemotherapy for this cancer might be suitable candidates for this study. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications like systemic chemotherapy, immunotherapy not specified in the protocol, and some vaccines are not allowed during the trial. 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 has shown that atezolizumab, when combined with chemotherapy and radiation, offers promising safety results. Studies have found that atezolizumab can significantly improve survival rates in patients with certain cancers, such as bladder cancer. Importantly, when paired with standard treatments, atezolizumab was well-tolerated by most patients, with no unexpected safety issues and generally manageable side effects.

The chemotherapy drugs in this trial, including cisplatin, gemcitabine, fluorouracil, and mitomycin, are well-known and have been used for many years. They are generally considered safe, though they can cause side effects like nausea, tiredness, or low blood counts. These side effects are common but usually manageable with proper medical care.

Overall, treatments in this study have a strong safety record based on previous research. However, as with any medical treatment, risks may still exist, and discussing personal concerns with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they are exploring the potential of adding atezolizumab, an immunotherapy drug, to the standard chemoradiotherapy for bladder cancer. Atezolizumab works by targeting and blocking the PD-L1 protein, which can help activate the immune system to attack cancer cells more effectively. Unlike traditional treatments that primarily rely on chemotherapy and radiation, incorporating atezolizumab could enhance the body's natural defenses against cancer. This combination approach aims to improve outcomes by potentially increasing the effectiveness of treatment and reducing the chance of disease progression.

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

Research shows that adding atezolizumab to chemoradiotherapy could be promising for treating bladder cancer. In this trial, some participants will receive chemoradiotherapy alone, using drugs like cisplatin and gemcitabine, which effectively kill bladder cancer cells. Other participants will receive chemoradiotherapy combined with atezolizumab. Studies have found that atezolizumab helps patients with urothelial cancer, a type of bladder cancer, live longer and delay disease progression. Specifically, in patients who maintained a negative status for ctDNA (a marker indicating disease activity), 95% were disease-free after one year, and 88% were disease-free after two years when treated with atezolizumab. Atezolizumab boosts the body's immune system to attack cancer cells, potentially leading to better outcomes. Combining these treatments aims to improve results for those with muscle-invasive bladder cancer. ^{3 4 6 7 8}

Who Is on the Research Team?

Parminder Singh

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

Adults with localized muscle invasive bladder cancer who've had a recent tumor removal and imaging, can participate. They must not have small cell carcinoma or certain other cancers in the last 24 months, no prior pelvic radiation or systemic chemotherapy for bladder cancer, and no severe liver disease or active infections. HIV-positive patients on stable treatment are eligible.

Inclusion Criteria

Patients must be offered the opportunity to participate in specimen banking for future studies

I may or may not be a candidate for bladder removal surgery.

I am HIV positive, on stable HIV treatment, with no current infections, a CD4 count over 250, and an undetectable viral load.

Exclusion Criteria

I have not had major surgery in the last 28 days.

I have not had a live vaccine in the last 4 weeks and won't need one during or up to 5 months after treatment.

I haven't needed treatment for an autoimmune disease in the last two years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo radiation therapy and receive chemotherapy with or without atezolizumab

7-8 weeks

Daily visits Monday-Friday for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Cisplatin
• Fluorouracil
• Gemcitabine
• Mitomycin
• Radiation Therapy

Trial Overview

The trial is testing if adding Atezolizumab (an immunotherapy drug) to standard chemoradiotherapy (using drugs like gemcitabine, cisplatin) improves outcomes in bladder cancer treatment. Patients will be randomly assigned to receive either the combination of treatments or just chemoradiotherapy.

How Is the Trial Designed?

Group I: Arm II (RT, chemotherapy, atezolizumab) Experimental Treatment 13 Interventions

Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5.

Group II: Arm I (RT, chemotherapy) Active Control 12 Interventions

Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Combination chemotherapy for metastatic bladder cancer, particularly the MVAC regimen, shows the highest effectiveness with complete response rates of 30-40%.

Chemotherapy is primarily used for palliative care in metastatic cases, but it can also serve as neoadjuvant treatment to shrink tumors before surgery, potentially preserving the bladder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Why use chemotherapy in cancer of the bladder? What are the initial limitations]. Maraninchi, D., Viens, P.[2013]

Neoadjuvant chemotherapy has been shown to improve overall survival in patients with locally advanced muscle-invasive bladder cancer, but its use in clinical practice remains low due to ongoing controversies regarding adjuvant chemotherapy.

Recent advancements include the approval of atezolizumab, a checkpoint inhibitor, for metastatic bladder cancer, alongside other promising therapies targeting mutational signatures, such as VEGF and HER2-directed agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises. Aragon-Ching, JB., Trump, DL.[2017]

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 Phase II study involving patients with invasive bladder cancer, a combined treatment of cisplatin and radiotherapy resulted in a 66% complete remission rate, indicating its effectiveness in tumor clearance.

The treatment was generally well-tolerated, with only two patients unable to complete the therapy due to acute toxicity, suggesting a favorable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined modality program with possible organ preservation for invasive bladder carcinoma: results of RTOG protocol 85-12. Tester, W., Porter, A., Asbell, S., et al.[2019]

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]

In a phase 2 study involving 45 patients with invasive bladder cancer, the combination of radiation therapy and atezolizumab resulted in a high pathologic complete response (pCR) rate of 84.4%, particularly in older patients and those with high PD-L1 expression.

The treatment was associated with acceptable toxicity, with 93.3% of patients experiencing adverse events, mostly mild to moderate, and only 13.3% experiencing grade 3 adverse events, indicating that this approach could be a viable bladder-preserving option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. Kimura, T., Ishikawa, H., Nagumo, Y., et al.[2023]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37537512/

Outcomes with atezolizumab in metastatic urothelial cancer

In this retrospective study, atezolizumab was an effective and tolerable treatment option for patients with mUC after progression to platinum-based ...

2.

pmc.ncbi.nlm.nih.gov

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

Efficacy and safety of atezolizumab in the treatment ...

Atezolizumab has demonstrated significant improvements in OS and PFS among patients with UC, offering crucial insights for decision-making in UC immunotherapy.

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S2405456920302698

Atezolizumab in Patients with Metastatic Urothelial ...

Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy.

4.

esmoopen.com

esmoopen.com/article/S2059-7029(24)01742-3/fulltext

final analysis from the phase II IMvigor210 trial

These final long-term data show that atezolizumab provides durable clinical benefit to a subset of patients with mUC. Abstract. Background. The ...

5.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2511885?query=featured_home

ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive ...

Among 357 patients with persistent ctDNA-negative status, disease-free survival was 95% at the end of the 1-year monitoring period and 88% at 2 ...

6.

roche.com

roche.com/media/releases/med-cor-2025-10-20b

Roche's Tecentriq showed significant overall and disease- ...

Tecentriq reduced the risk of death by 41% and the risk of disease recurrence or death by 36% compared with placebo1; IMvigor011 is the ...

7.

gene.com

gene.com/media/press-releases/15084/2025-10-19/genentechs-tecentriq-showed-significant-

Genentech: Press Releases | Sunday, Oct 19, 2025

Tecentriq reduced the risk of death by 41% and the risk of disease recurrence or death by 36% compared with placebo.

8.

onclive.com

onclive.com/view/ctdna-guided-adjuvant-atezolizumab-boosts-dfs-os-in-muscle-invasive-bladder-cancer

ctDNA-Guided Adjuvant Atezolizumab Boosts DFS, OS in ...

Additionally, ctDNA-positive patients in the atezolizumab arm experienced a median OS of 32.8 months (95% CI, 27.7-not evaluable [NE]) compared ...