Neoadjuvant Pembrolizumab for Muscle-invasive Urothelial Bladder Carcinoma
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|ClinicalTrials.gov Identifier: NCT02736266|
Recruitment Status : Recruiting
First Posted : April 13, 2016
Last Update Posted : March 3, 2017
Patients with T2-T4a N0 urothelial bladder carcinoma (UBC) with residual disease after transurethral resection of the bladder (TURB, surgical opinion, cystoscopy or radiological presence) will receive 3 cycles of pembrolizumab (MK-3475) at the dose of 200mg 3 weekly prior to surgery (radical cystectomy). Cystectomy will be planned to be done within 3 weeks of the last dose (accounting for a total of 9 weeks).
Computed tomography (CT) scan and fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan will be done during screening and before surgery. After cystectomy, patients with the evidence of pathologic stage T3-4 (pT3-4) and/or pathologically node-positive disease will be managed according to local guidelines. Further anti programmed-death (PD)-1 or anti PD-ligand 1 (PD-L1) therapy will not be given post-operatively.
PD-L1 status will be centralized and assessed on TURB specimen using an anti-PD-L1 antibody (Ab) and a prototype immunohistochemical (IHC) assay. PD-L1 positivity will be defined as any staining in the stroma or in ≥1% of tumor cells.
Pathologic complete response (pCR) is the primary endpoint. All patients enrolled who receive at least 1 cycle of study drug will be includes in the intention-to-treat (ITT) analysis.
The alternative hypothesis (H1) is pCR ≥20% and null hypothesis (H0) pCR≤10%. A 2-stage design will be used to estimate the number of pts required. Out of 90 pts overall, with the first stage of 49 pts, ≥6 pCR will be required in the first stage, and ≥13 pCR in the whole study population (80% power and a 2-sided test of significance at the 10% level).
Correlative research on tissue/blood samples will include immune-cell profiling in tumor and blood during Pembrolizumab, cytokine assessment, and molecular profiling of tumor samples.
|Condition or disease||Intervention/treatment||Phase|
|Urothelial Bladder Carcinoma||Drug: Pembrolizumab (MK-3475)||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||90 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open Label, Single-arm, Phase 2 Study of Neoadjuvant Pembrolizumab (MK-3475) Before Cystectomy for Patients With Muscle-invasive Urothelial Bladder Cancer.|
|Actual Study Start Date :||February 27, 2017|
|Estimated Primary Completion Date :||January 2019|
|Estimated Study Completion Date :||June 2019|
Experimental: Pembrolizumab (MK-3475)
Pembrolizumab (MK-3475) will be administered at the dose of 200mg, as a 30-minute intravenous infusion, every 3 weeks, for a total of 3 cycles prior to radical cystectomy.
Drug: Pembrolizumab (MK-3475)
Pembrolizumab given intravenously in 30 min. infusion every 3 weeks
Other Name: Keytruda
- Pathologic complete response [ Time Frame: At the time of radical cystectomy (within 9 weeks of the first dose of pembrolizumab) ]Absence of residual viable tumor in the radical cystectomy specimen
- Adverse events [ Time Frame: Up to 2 years ]Number of patients developing side effects
- Percentage of treatment-related delay in surgery [ Time Frame: Starting at week 9 ]Number of patients undergoing cystectomy later than 12 weeks after pembrolizumab treatment
- Frequency of treatment-related adverse events [ Time Frame: Up to 1 year ]Number of patients developing side effects
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02736266
|Contact: Andrea Necchi, MDemail@example.com|
|Fondazione IRCCS Istituto Nazionale dei Tumori||Recruiting|
|Milano, Mi, Italy, 20133|
|Contact: Andrea Necchi, MD +390223902402 firstname.lastname@example.org|
|Principal Investigator: Andrea Necchi, MD|