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Clinical Trial 20353

Cancer Type: Genitourinary
Study Type: Treatment
NCT#: NCT03775265

Phase: Phase III
Principal Investigator: Grass, George (Daniel)

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study Title

S1806, Phase III Randomized Trial of Concurrent Chemoradiotherapy with or without Atezolizumab in Localized Muscle Invasive Bladder Cancer

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.

Objective

Primary Objective: To compare bladder intact event-free survival (BI-EFS) for concurrent chemoradiation therapy (CRT) with and without atezolizumab in localized muscle invasive bladder cancer (MIBC). Secondary Objectives: - To compare overall survival between the two arms. - To compare modified bladder intact event-free survival (mBI-EFS see Section 10) including cancer related death between arms. - To compare complete and partial pathologic response between arms at 3 months after completing chemoradiation therapy. - To estimate metastases-free survival by arm. - To compare the qualitative and quantitative adverse events from each arm. - To estimate the rate of non-muscle invasive bladder cancer recurrence by arm. - To estimate the rate of salvage cystectomy and reasons for cystectomy by arm. - To compare mean patient-reported global quality of life (QOL) at week 54 using the EORTC QLQ-C30 Global Health Status (GHS) subscale score between patients with localized muscle-invasive bladder cancer randomized to chemoradiation with vs. without atezolizumab.

Treatments

Therapies

Chemotherapy (NOS); Immunotherapy; Radiotherapy

Medications

5-fluorouracil (); Atezolizumab (Tecentriq); Gemzar (gemcitabine); cisplatin (); gemcitabine (); mitomycin c ()

Inclusion Criteria

Inclusion Criteria:

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.

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 => Patients must be 18 years of age or older

Patient may or may not be radical cystectomy candidates.

Adequate organ function as defined in protocol

Patients who can complete Patient-Reported Outcome instruments in English or Spanish must agree to complete the EORTC QLQ-C30, the EORTC QLQ-BLM30, the EPIC Bowel Assessment, and the EQ-5D-5L per protocol schedule of assessment.

As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

Exclusion Criteria

Exclusion Criteria:

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 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 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: (a) Anti-cancer systemic chemotherapy or biological therapy not specified in the protocol. (b) Immunotherapy not specified in this protocol. (c) Systemic or intravesical use of any non-study anti-cancer agent (investigational or non-investigational). (d) Investigational agents other than atezolizumab. (e) Live vaccines: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, bacillus Calmette-Guerin (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. (f) Glucocorticoids for any purpose other than to modulate symptoms from an event of suspected immunologic etiology. The use of physiologic doses of corticosteroids (defined as 10 mg prednisone) are acceptable, however site investigators should consult with the study chair for any dose higher than 10 mg prednisone. Dexamethasone 4 mg iv with chemotherapy to prevent nausea is allowed. (g) RANKL infusion: Concurrent denosumab (which binds the cytokine RANKL) for any known indication is prohibited due to interaction with study medication.

Patients must not have a major surgical procedure within 28 days prior to randomization. If patient had any surgical procedure then they should have recovered to full presurgical performance status and surgical adverse events should have resolved to grade => Patients must not have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to randomization. Exceptions: (a) Patients may have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea). (b) The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. Physiological doses equivalent of 10 mg prednisone daily are allowed. Short term steroids given as antiemetic therapy, e.g. 4 mg dexamethasone or equivalent once a week, is allowed.

Additional criteria apply

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