Biochemical relapse in patients who have undergone radical cystectomy because of muscle-invasive transitional cell carcinoma of the urinary bladder MedDRA version: 21.1 Level: PT Classification code 10066754 Term: Bladder transitional cell carcinoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Tecentriq
Product Name: Atezolizumab
Product Code: L01XC32
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
CAS Number: 1380723-44-3
Current Spo
Sponsors
Aarhus University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • =18 years of age at the time of signing the Informed Consent Form • For male study subjects: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm. • Signed Informed Consent Form • ECOG PS 0, 1 or 2 • Is, according to the Investigator’s judgement, able to comply with the trial protocol • Ability to understand the Participant Information Sheet orally and in writing • Preoperative PET/CT of thorax, abdomen, and pelvis with no suspicion of organ metastases or untreated lymph node metastasis* • Study Subjects undergoing radical cystectomy due to histopathological or clinical documented muscle invasive urothelial carcinoma (including subtypes) stage cT2-4a in the urinary bladder following NAC** in cisplatin-fit Study Subjects. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 282
Exclusion criteria
Exclusion criteria: • Subjects undergoing non-radical cystectomy for palliative reasons • Non-radical surgery estimated intraoperative • Other histology of BC than urothelial carcinoma – mixed tumours with urothelial features are allowed • Concomitant invasive cancer within 5 years other than non-melanoma skin cancer and prostate cancer without metastasis • Known contraindication to immunotherapy • A history of autoimmune disease. Study Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. • Study Subjects who meet any of the following criteria will be excluded from study entry: • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment • HIV positive • History of pneumonitis (History of radiation pneumonitis in the radiation field (fibrosis) is permitted. • Hepatitis B or hepatitis C infection • Subjects who have received a live, attenuated vaccine within 28 days prior to enrolment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Complete response (CR) after treatment with investigational agent initiated by ctDNA positive status after radical cystectomy (with or without concomitant visible metastases on CT). Data will be compared to available historical data on response to PD-1 / PD-L1 targeted agents. CR in the current study is defined as ctDNA negative status in the last plasma samples taken during IO treatment combined with negative imaging (CT) at the same time point after treatment. Thus, any metastasis visible on CT at the time of treatment initiation should undergo complete response. In Study Subjects without visible metastasis on CT at the time of treatment, initiation should result in unchanged status on CT.;Timepoint(s) of evaluation of this end point: 12 months after investigational treatment initiation;Main Objective: To investigate the response rate and oncological outcome of systemic immunotherapy administered at the time of biochemical relapse (ctDNA positive test) in Study Subjects who have undergone NAC followed by radical cystectomy because of MIBC. Long term survival of Study Subjects with positive ctDNA treated with immunotherapy will be compared to available historical data from clinical immunotherapy trials where Study Subjects are treated at the time of recurrence diagnosed by conventional CT routine follow-up.;Secondary Objective: Not applicable | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Duration of freedom from clinical relapse in Study Subjects showing decrease or stabilization of ctDNA level after treatment with investigational agent • Overall survival after cystectomy in Study Subjects having biochemical relapse • Cancer specific survival after cystectomy in Study Subjects having biochemical relapse • Recurrence free survival after cystectomy in Study Subjects having biochemical relapse • Cancer specific survival after cystectomy in Study Subjects having biochemical relapse stratified for potential predictive biomarkers for response to treatment • Response rate to investigated agent stratified for PD-L1 expression and other predictive biomarkers like TMB, immune cell infiltration, tumor subtypes etc. • Response rate to neoadjuvant chemotherapy measured as down staging to T0 or T<2 at cystectomy and correlation with level of ctDNA in plasma and urine samples • Time to recurrence seen on imaging (symptomatic or asymptomatic) • Quality of life assessment using the EORTC QLQ 30 (Quality of life in cancer patients) and QLQ-BLM30 (Quality of life in patients with Muscle Invasive Bladder Cancer) • Cost-effectiveness modelling analysis • Prolonged CR defined as ctDNA negative status in the plasma samples taken 12 months following completion of IO combined with negative imaging (CT) at the same time point, without administration of other oncologic treatment;Timepoint(s) of evaluation of this end point: January, 01 2028 LVLS | — |
Countries
Denmark
Contacts
Public ContactJørgen Bjerggaard Jensen
Aarhus University Hospital
Outcome results
None listed