Phase III Randomized Trial of Concurrent Chemoradiotherapy With or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer

Plain English Summary

Chemoradiotherapy With or Without Atezolizumab in Treating Patients With Localized Muscle Invasive Bladder Cancer is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Bladder Urothelial Carcinoma, Muscle Invasive Bladder Carcinoma, Stage II Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8. Tests if adding Atezolizumab to radiation and chemotherapy improves outcomes for localized muscle invasive bladder cancer. For patients with bladder cancer who haven't had previous treatment for this type of cancer. Participation involves multiple visits for scans, biopsies, and treatments over several months. Alternatives include standard radiation and chemotherapy without Atezolizumab. The trial aims to enroll 475 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if diagnosed with localized muscle invasive bladder cancer within 120 days, no prior systemic chemotherapy, and no prior pelvic radiation. Not eligible if had urothelial carcinoma at another site within 24 months, received prior systemic therapy for bladder cancer, or had T4b disease. Age: 18+ years, generally in good health, no other serious health conditions. This trial is studying Bladder Urothelial Carcinoma, Muscle Invasive Bladder Carcinoma, Stage II Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures survival, helping patients understand how well the treatment works to keep the bladder intact and alive. The specific primary outcome measures are: Bladder intact event-free survival (BI-EFS) (From the date of randomization to the first documentation of a BI-EFS event, assessed up to 5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill a gap in treatment options for localized muscle invasive bladder cancer by potentially improving survival and quality of life. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Bladder Urothelial Carcinoma, Muscle Invasive Bladder Carcinoma, Stage II Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8, where improved treatment options are needed.

Investor Insight

The market for bladder cancer treatments is large, with few approved options, making this trial significant for investors. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you have any other health conditions or are taking other medications. You will have multiple visits for scans, biopsies, and treatments over several months. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 475 participants

Interventions

• DRUG: Atezolizumab — Given IV
• PROCEDURE: Biopsy of Bladder — Undergo a bladder biopsy
• DRUG: Cisplatin — Given IV
• PROCEDURE: Computed Tomography — Undergo CT or MRI
• PROCEDURE: Cystoscopy — Undergo a cystoscopy

Primary Outcomes

• Bladder intact event-free survival (BI-EFS) (From the date of randomization to the first documentation of a BI-EFS event, assessed up to 5 years)

Secondary Outcomes

• Overall survival (OS) (From date of randomization to death from any cause, assessed up to 5 years)
• Modified bladder intact event-free survival (mBI-EFS) (From date of randomization to the first documentation of a mBI-EFS event, assessed within 90 days)
• Biopsy response (At 18 weeks)
• Complete response duration (From the date of the biopsy documenting the complete response to the time of muscle invasive recurrence, local progression, evidence of metastatic disease or death due to any cause, assessed at 18 weeks)
• Progression-free survival (From date of randomization to first radiologic or histologic evidence of local progression, nodal or distant metastasis, or death due to any cause, assessed up to 5 years)

Full Eligibility Criteria

Inclusion Criteria:

* STEP 1 REGISTRATION: If this will be the first patient from a registering site to receive a given RT modality (3DCRT vs. IMRT), the site must first submit pre-RT planning documents within 3 days of Step 1 registration and receive approval from Imaging and Radiation Oncology Core (IROC) before randomizing the patient to Step 2. If this will not be the first patient to receive a specific RT modality, the patient should be immediately randomized to Step 2 on the same day.
* STEP 2 RANDOMIZATION: If patient required review of pre-RT planning, randomization must occur within 14 days of initial registration.
* Patients must have histologically proven, T2-T4a N0M0 urothelial carcinoma of the bladder within 120 days prior to randomization and no intervening treatment between the histologic proof and randomization. Patients with mixed urothelial carcinoma will be eligible for the trial, but the presence of small cell carcinoma will make a patient ineligible. Patients with lymph nodes \>= 1.0 cm in shortest cross-sectional diameter on imaging (computed tomography \[CT\]/magnetic resonance imaging \[MRI\] of abdomen and pelvis) must have a biopsy of the enlarged lymph node showing no tumor involvement within 70 days prior to randomization. These patients may be suitable for neoadjuvant chemotherapy and radical cystectomy and are eligible for this trial if they seek out a bladder sparing treatment strategy, however patients who have received prior systemic chemotherapy for bladder cancer are not eligible for the trial.
* Patients must undergo a transurethral resection of bladder tumor (TURBT) within 70 days prior to randomization. In a situation where a patient is referred from outside to the enrolling institution, patient must have a repeat office cystoscopy by the urologist who will be following the patient on the clinical trial to assess the adequacy of the prior TURBT. This cystoscopy can be performed in urologist office without general anesthesia. Patient may then undergo repeat TURBT if deemed necessary as standard of care by the treating urologist. Patients may have either completely or partially resected tumors as long as the treating urologist attempted maximal resection. Patient must not have T4b disease
* Patients must undergo radiological staging within 70 days prior to randomization. Imaging of chest, abdomen, and pelvis must be performed using CT or MRI. Patients must not have evidence of T4bN1-3 disease. Eligibility is based on the local radiology report.
* Patients with hydronephrosis are eligible if they have unilateral hydronephrosis and kidney function meets criteria specified.
* Patients must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder within the previous 24 months except Ta/T1/carcinoma in situ (CIS) of the upper urinary tract including renal pelvis and ureter if the patient had undergone complete nephroureterectomy.
* Patients must not have diffuse CIS based on cystoscopy and biopsy.
* Patient must be planning to receive one of the protocol specified chemotherapy regimens.
* All adverse events associated with any prior surgery and intravesical therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade =\< 2 prior to randomization.
* Patient must not have received any systemic chemotherapy for their bladder cancer.
* Patient must not have had prior pelvic radiation.
* Patients must not have received prior treatment for muscle invasive bladder cancer including neoadjuvant chemotherapy for the current tumor.
* Patients must not have received any systemic therapy (including, but not limited to, interferon alfa-2b, high dose IL-2, pegylated interferon \[PEG-IFN\], anti-PD-1, anti-PD-L1), for non-muscle invasive bladder cancer. Prior intravesical bacillus Calmette-Guerin (BCG), interferon, and intravesical chemotherapy are allowed.
* Patients must not have received any of the following prohibited therapies within 28 days prior to randomization or be planning to receive any of the following prohibited therapies during protocol treatment:

  * Anti-cancer systemic chemotherapy or biological therapy not specified in the protocol.
  * Immunotherapy not specified in this protocol.
  * Systemic or intravesical use of any non-study anti-cancer agent (investigational or non-investigational).
  * Investigational agents other than atezolizumab.
  * Live vaccines: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines, and are not allowed. Prior administration of intravesical BCG is allowed.
  * Glucocorticoids for any purpose other than to modulate symptoms from an event of suspected immunologic etiology. T

Trial Locations

• Mayo Clinic Hospital in Arizona, Phoenix, Arizona, United States
• Mayo Clinic in Arizona, Scottsdale, Arizona, United States
• Banner University Medical Center - Tucson, Tucson, Arizona, United States
• University of Arizona Cancer Center-North Campus, Tucson, Arizona, United States
• Sutter Auburn Faith Hospital, Auburn, California, United States
• Sutter Cancer Centers Radiation Oncology Services-Auburn, Auburn, California, United States
• Alta Bates Summit Medical Center-Herrick Campus, Berkeley, California, United States
• Mercy Cancer Center - Carmichael, Carmichael, California, United States
• Mercy San Juan Medical Center, Carmichael, California, United States
• Mercy Cancer Center - Elk Grove, Elk Grove, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Bladder Urothelial Carcinoma
• Muscle Invasive Bladder Carcinoma
• Stage II Bladder Cancer AJCC v8
• Stage IIIA Bladder Cancer AJCC v8
• Stage IV Bladder Cancer AJCC v8
• Renal Cell Carcinoma
• Prostate Cancer
• Kidney Cancer
• Cancer of the Ureter
• Cancer of the Urethra

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