Chemoradiotherapy + Atezolizumab for Bladder Cancer

Recruiting at 426 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

475 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab in treating patients with localized muscle invasive bladder cancer. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. 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 cells to grow and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab.

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 the combination of chemoradiotherapy and atezolizumab safe for bladder cancer treatment?

The combination of chemoradiotherapy and atezolizumab for bladder cancer has been studied for safety. Atezolizumab is generally well-tolerated, even in patients with kidney issues, and is expected to work well with radiation therapy. Cisplatin, a component of chemoradiotherapy, can cause side effects like nausea and bone marrow suppression, but these are usually manageable. ^{1 2 3 4 5}

What makes the treatment of chemoradiotherapy plus atezolizumab unique for bladder cancer?

This treatment combines chemoradiotherapy with atezolizumab, an immune therapy that helps the body's immune system attack cancer cells, offering a bladder-preserving option for patients who cannot undergo surgery. Atezolizumab is unique because it targets PD-L1, a protein that helps cancer cells evade the immune system, and is particularly beneficial for patients who are not eligible for traditional cisplatin chemotherapy. ^{4 6 7 8 9}

What data supports the effectiveness of the drug Atezolizumab when used with chemoradiotherapy for bladder cancer?

Research shows that combining platinum-based chemotherapy with radiation therapy can be effective for locally advanced bladder cancer, with a high rate of complete response and survival benefits. Neoadjuvant cisplatin-based chemotherapy has also been shown to improve survival in patients with metastatic bladder cancer, suggesting potential benefits when combined with other treatments like Atezolizumab. ^{10 11 12 13 14}

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]

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]

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]

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]

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]

Citations

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

Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. [2022]

2. France pubmed.ncbi.nlm.nih.gov

[Radiotherapy and chemotherapy in infiltrating bladder tumors]. [2006]

3. Japan pubmed.ncbi.nlm.nih.gov

[Concurrent platinum-based chemotherapy and radiotherapy for locally advanced bladder cancer]. [2021]

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

[Why use chemotherapy in cancer of the bladder? What are the initial limitations]. [2013]

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

Neoadjuvant chemotherapy for bladder cancer. [2022]

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

Combined modality program with possible organ preservation for invasive bladder carcinoma: results of RTOG protocol 85-12. [2019]

7. Ireland pubmed.ncbi.nlm.nih.gov

A concomitant tumour boost in bladder irradiation: patient suitability and the potential of intensity-modulated radiotherapy. [2018]

8. Pakistan pubmed.ncbi.nlm.nih.gov

Impact of Gemcitabine and Cisplatin with radiotherapy in locally advanced or metastatic transitional cell carcinoma of urinary bladder. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Bladder preservation therapy in combination with atezolizumab and radiation therapy for invasive bladder cancer (BPT-ART) - A study protocol for an open-label, phase II, multicenter study. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Phase II study of cis-diammine(glycolato)platinum, 254-S, in patients with advanced germ-cell testicular cancer, prostatic cancer, and transitional-cell carcinoma of the urinary tract. 254-S Urological Cancer Study Group. [2019]

11. United States 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. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. [2019]

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

Nod for Atezolizumab in Advanced Bladder Cancer. [2018]

14. England pubmed.ncbi.nlm.nih.gov

Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises. [2017]