Testing Anti-Cancer Drugs Erdafitinib With or Without Atezolizumab in Patients With Localized Bladder Cancer Not Able to Receive Cisplatin Chemotherapy, NERA Trial

Urothelial Carcinoma Clinical Trial

Official title: An Open Label, Randomized Phase II Study Neoadjuvant Erdafitinib With or Without Atezolizumab in Cisplatin-Ineligible Patients With Muscle Invasive Bladder Cancer (NERA)

Status Withdrawn

Clinical Trial Summary

This phase II trial compares the effect of erdafitinib alone to using the combination of erdafitinib and atezolizumab in treating patients with bladder cancer whose tumor invades the muscular bladder wall (muscle invasive)and who are ineligible for treatment with a chemotherapy drug called cisplatin. This trial also determines whether these treatment approaches are better than the usual approach for treating this type of cancer. The usual approach for treatment of someone with muscle invasive bladder cancer is chemotherapy with a drug called cisplatin followed by surgery (most common), or chemoradiation (radiation combined with chemotherapy) to the bladder (in some patients). However, half of the patients cannot get cisplatin due to safety concerns. This study has a screening step. The purpose of this step is to test patient's tumor to find out if it has a specific change (alteration) in the fibroblast growth factor receptor (FGFR) gene to determine patient's eligibility for this trial. Alteration of the FGFR gene causes bladder cancer cells to grow and divide abnormally. Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein. This may help keep cancer cells from growing and may kill them. 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 erdafitinib alone or in combination with atezolizumab may help to shrink tumor cells at the time of surgery better than the usual treatment in muscle invasive bladder cancer.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To evaluate pathologic complete response (pCR) rates at radical cystectomy (RC) following neoadjuvant erdafitinib with or without atezolizumab in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) and susceptible FGFR3/2.

SECONDARY OBJECTIVES:

I. To determine the rate of pathologic downstaging (=< pT1N0M0) among patients who receive RC.

II. To determine the clinical complete response (cCR) rate in patients who do not undergo planned RC.

III. To determine pCR + cCR. IV. To evaluate 2-year disease-free survival (DFS). V. To evaluate the overall survival (OS) rate at 2 years. VI. To evaluate the safety and tolerability of study treatment as well as surgical complications in the RC group.

EXPLORATORY OBJECTIVES:

I. To correlate the reduction of plasma circulating tumor deoxyribonucleic acid (DNA) (ctDNA) during study treatment and the surveillance period with disease outcomes (pCR and cCR, pathologic downstaging, 2-year DFS and OS).

II. To correlate tumor response with baseline tissue, ctDNA FGFR3/2 mutation status, and molecular signature.

III. To characterize the baseline tumor tissue immune profile of FGFR3/2-aberrant tumors including programmed death-ligand 1 (PD-L1) expression, tumor mutational burden (TMB), and T cell infiltration (PD-L1 expression, peripheral blood mononuclear cell (PBMC), T cell receptor [TCR] repertoire).

IV. To characterize the changes in the above tumor tissue immune profile following study treatment.

V. To correlate baseline tumor tissue TMB with disease outcomes (pCR and cCR, pathologic downstaging, 2-year DFS and OS).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive erdafitinib orally (PO). Patients undergo collection of blood and computed tomography (CT)/magnetic resonance imaging (MRI) at various time points throughout the trial and colposcopy at baseline.

ARM II: Patients receive erdafitinib PO and atezolizumab intravenously (IV). Patients undergo collection of blood and CT/MRI at various time points throughout the trial and colposcopy at baseline. ;

Related Conditions & MeSH terms

• Bladder Carcinoma
• Bladder Urothelial Carcinoma
• Carcinoma
• Carcinoma, Transitional Cell
• Muscle Invasive Bladder Carcinoma
• Renal Pelvis and Ureter Urothelial Carcinoma
• Stage II Bladder Cancer AJCC v8
• Stage III Bladder Cancer AJCC v8
• Stage IVA Bladder Cancer AJCC v8
• Urinary Bladder Neoplasms
• Urothelial Carcinoma

• NCT number: NCT05564416
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Withdrawn
• Phase: Phase 2
• Start date: October 12, 2023
• Completion date: November 3, 2023