Neoadjuvant Immune Checkpoint Inhibitor Treatment in Urothelial Cancer
ConditionUrogenital Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-99
SponsorQueen Mary University of London
About this trial
This study is being carried out to see if the drug atezolizumab can reduce the size of tumours in patients with types of urothelial cancer before surgery. Atezolizumab is designed to stop a protein called PD-L1 (programmed death-ligand 1) being expressed on the cancer, allowing the immune system to recognise the tumour cells as foreign bodies and attack them. Atezolizumab has been shown to have activity in urothelial cancer which has spread.
There two cohorts for this trial. One cohort will investigate the most common histological type of urothelial cancer (transitional cell carcinoma) outside the bladder, for example in the upper urinary tract. The other cohort will investigate rarer histological subtypes (such as such as squamous cell or adenocarcinoma) of urothelial cancer throughout the entire urinary system.
This study will be recruiting patients from hospitals in the UK, France and Spain. If a patient is eligible for the study and decides to take part, they will receive up to two 3-weekly cycles of atezolizumab. 4-8 weeks after being enrolled, the patient will have an operation to remove the bladder (cystectomy) or the kidney, ureter and part of the bladder (nephroureterectomy or distal ureteral resection) as per normal practice. Following surgery, they will attend three hospital visits (4,12 and 24 weeks after surgery) and their disease progress/survival will be followed over the next 2 years. The clinical team will compare the patient's tumour tissue samples,scan results and blood results from before and after treatment with atezolizumab in order to see how well the drug works and if it is safe. Many of the procedures involved in this study are offered as standard care and participation in this trial will not delay surgery.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Hydronephrosis
Tumour size >2cm on cross sectional imaging
High grade cytology
High grade biopsy
Disqualifiers
Pregnant and lactating female patients.
Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
Previously intravenous chemotherapy for urothelial cancer.
Patients with prior allogeneic stem cell or solid organ transplantation.
Trial design
Design model
Single group
Treatments tested in this trial
Atezolizumab
DrugPatients receive 2 x 3-weekly cycles of Atezolizumab (one infusion on the first day of each cycle) prior to cystectomy surgery.
Treatment groups
58 Participants
are divided into 1 treatment groupGroup A: AtezolizumabExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Pathological complete response rate (pCRR)
No microscopic evidence (pT0/Tis/Cis) of residual disease in the bladder based on histological evaluation of the resected bladder specimen collected during cystectomy (post-treatment) \[Bladder Cohort\] \- No microscopic evidence (pT0/Tis/Cis) of residual disease in the renal pelvis or ureter in the resected sample collected during radical surgery for upper tract disease (post-treatment) \[UTUC Cohort\]
Time frame
At surgery (4-8 weeks after patient registration)2
Assessment on immune parameters
ynamic changes in T cell subpopulations (CD8 and/or CD3) measured in tumour samples collected pre- and post-treatment.
Time frame
Samples acquired at surgery (4-8 weeks after patient registration)Secondary outcomes
1
Evaluate the safety and tolerability of atezolizumab when given in the neoadjuvant setting
Incidence, nature and severity of Adverse Events graded according to NCI-CTCAE v5.0. Surgical complications will be assessed by the Clavien-Dindo scoring system.
Time frame
Adverse Events will be collated during treatment and up to 24 weeks post-cystectomy or post-radical surgery. Surgical complications will be assessed at the 4wk and 12 week follow-up visits.2
Assess the efficacy of atezolizumab given in the neoadjuvant setting with respect to anti-tumour effects as measured by Investigator assessed radiological response (RR)
RR defined as a ≥30% decrease in tumour diameter from the baseline scan based on local investigator assessments.
Time frame
Assessed at CT scan pre-surgery.3
Assess the efficacy of atezolizumab given in the neoadjuvant setting with respect to anti-tumour effects based on Investigator assessed disease-free survival (DFS)
DFS defined as time between the date of enrolment to first evidence of relapse based on local investigator assessments or death, whichever occurs first.
Time frame
Evaluated at 12 weeks, 24 weeks, 12 months, and 24 months post-surgery.4
Assess the efficacy of atezolizumab given in the neoadjuvant setting with respect to overall survival (OS)
OS, defined as the time between the date of enrolment and death due to any cause.
Time frame
Evaluated at 12 weeks, 24 weeks, 12 months, and 24 months post-surgery.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Queen Mary University of London
Lead sponsor
Hoffmann-La Roche
Collaborator
Source ClinicalTrials.gov