An Open Label, Single-arm, Phase 2 Study of Neoadjuvant Nivolumab and Nab-paclitaxel Before Radical Cystectomy for Patients With Muscle-invasive Bladder Cancer (NURE-Combo) (NURE-Combo)
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|ClinicalTrials.gov Identifier: NCT04876313|
Recruitment Status : Recruiting
First Posted : May 6, 2021
Last Update Posted : April 6, 2022
|Condition or disease||Intervention/treatment||Phase|
|Muscle-Invasive Bladder Carcinoma||Drug: Nivolumab + Nab-paclitaxel Drug: Nivolumab||Phase 2|
This is a Phase 2, single-center, open-label, non-randomized study in patients with muscle-invasive urothelial carcinoma of the bladder.
The general framework of the study will be as follows:
A transurethral resection of the bladder for biopsy, histological characterization, and local staging will be executed first. With the aim to improve the sensitivity of CT scan in assessing pelvic lymph-nodes and better assess the local extent of bladder tumor, computed tomography (CT) scan, 18FDG-PET/CT scan, and multiparametric bladder MRI (mpMRI) will be done during screening and before cystectomy to stage and evaluate response.
Eligible patients will receive neoadjuvant treatment: 360 mg nivolumab IV on Day 1 plus 125 mg/m2 nab-paclitaxel on Day 1 and 8, in a 21-day cycle.
A total of 4 cycles are planned before surgery. Surgery will be planned at the time of study inclusion to be done within 3 weeks of the last dose of study drug.
Dose reductions will be applied depending on the severity of AEs, and treatment interruption or discontinuation criteria will be fully described in the protocol.
After surgery, patients will receive 12-month adjuvant therapy with nivolumab 360 mg IV, every 3 weeks.
RECIST v1.1 criteria will be used to assess patient response to treatment by determining tumor size and PFS. Screening assessments should be performed no more than 21 days prior to the start of study treatment. Following the screening assessment, subsequent assessments will be carried out after the administration of the study drugs prior to cystectomy. If an unscheduled assessment is performed and the patient has not progressed, the results should be reported at the next scheduled visit. The method of tumor assessment used at baseline e.g. CT or MRI scans chest, abdomen, pelvis, must be used at each sub-sequent follow-up assessment.
Patients will be monitored carefully for the development of adverse events and will be monitored for clinical and/or radiographic evidence of disease progression according to usual standards of clinical practice. Adverse experiences will be evaluated according to criteria outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Patients with muscle-invasive urothelial bladder carcinoma, not eligible or denying standard neoadjuvant therapy|
|Masking:||None (Open Label)|
|Official Title:||An Open Label, Single-arm, Phase 2 Study of Neoadjuvant Nivolumab and Nab-paclitaxel Before Radical Cystectomy for Patients With Muscle-invasive Bladder Cancer|
|Actual Study Start Date :||January 27, 2022|
|Estimated Primary Completion Date :||December 2024|
|Estimated Study Completion Date :||June 2025|
Experimental: Combined Drugs
Participants received 4x3 weekly cycles of 360 mg Nivolumab + 125 mg/m^2 Nab-paclitaxel IV on days 1 and 8, then they had cystectomy after that partecipants received adjuvant nivolumab 360 mg IV Q3W X13 cycles
Drug: Nivolumab + Nab-paclitaxel
4x3 weekly cycles of 360 mg nivolumab + 125 mg/m^2 nab-paclitaxel IV on days 1 and 8
Other Name: Nivolumab + Abraxane
360 mg IV Q3W x 13 cycles
Other Name: Adjuvant Nivolumab
- Pathological complete response [ Time Frame: Change from Screening after radical cystectomy ]To assess whether nab-paclitaxel plus nivolumab results in pathological complete response (herein referred to as either "ypT0N0M0" or "pCR") in patients with clinical T2-4aN0M0 MIBC who cannot receive or refuse to receive cisplatin-based chemotherapy. Absence of any residual viable tumor in the radical cystectomy specimen. Two independent pathologists, blinded to the study findings, with >10 years of experience in genitourinary tumors will independently evaluate the response.
- pathological downstaging [ Time Frame: screening, 14 days after final combined treatment, 3 weeks until 12 months post-radical cystectomy, 3 months until 12 months post-adjuvant nivolumab ]To evaluate the proportion of patients who will be pathological downstaged to ypT<=1N0M0.
- radiological response [ Time Frame: screening, 14 days after final combined treatment, 3 weeks until 12 months post-radical cystectomy, 3 months until 12 months post-adjuvant nivolumab ]To evaluate radiological response on those patients with measurable disease. Response (CR and PR) will be assessed after the full neoadjuvant course of 4 cycles.
- Number of participants with treatment related adverse events as assessed by CTCAE v5.0 and EAU recommendations [ Time Frame: From date of Screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 40 months ]To evaluate the surgical and medical safety of neoadjuvant combination therapy, as well as of the adjuvant nivolumab therapy.
- event-free survival [ Time Frame: From date of Screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 40 months ]To assess event-free survival in the total population and in the subgroups according to the pathological response.
- overall survival [ Time Frame: From date of Screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 40 months ]To assess overall survival in the total population and in the subgroups according to the pathological response.
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): NCT04876313
|Contact: Andrea Necchi||+39 firstname.lastname@example.org|
|Contact: Rossella Miotti||+39 0226435789||Miotti.email@example.com|
|Genitourinary Medical Oncology - IRCCS San Raffaele Hospital and Scientific Institute||Recruiting|
|Milan, MI, Italy, 20132|
|Contact: Andrea Necchi +39 0226435789 firstname.lastname@example.org|
|Contact: Rossella Miotti +39 0226435789 Miotti.email@example.com|
|Principal Investigator: Andrea Necchi|