Ignite Creation Date:
2025-12-24 @ 1:06 PM
Ignite Modification Date:
2026-01-05 @ 9:38 AM
Study NCT ID:
NCT03387761
Status:
COMPLETED
Last Update Posted:
2025-03-05
First Post:
2017-11-24
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Neo-Adjuvant Bladder Urothelial Carcinoma COmbination-immunotherapy
Sponsor:
The Netherlands Cancer Institute
Organization:
Study Overview
Official Title:
Phase 1B Study to Assess Safety and Efficacy of Neo-Adjuvant Bladder Urothelial Carcinoma COmbination-immunotherapy (NABUCCO)
Status:
COMPLETED
Status Verified Date:
2025-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NABUCCO
Brief Summary:
In cohort 1 of this study, we used an attenuated schedule of neoadjuvant ipilimumab and nivolumab. In the multicenter extension (cohort 2), 30 patients were randomized between two neoadjuvant treatment schemes, both based upon an attenuated schedule of neoadjuvant ipilimumab and nivolumab.Both cohorts are completed.
Detailed Description:
This is an open-label phase Ib trial to evaluate three different schedules of preoperative ipilimumab and nivolumab. Urothelial cancer patients will be included that are diagnosed with either:
* cT3-4aN0M0 OR
* T1-4aN1-3M0
Cohort 1 (n=24):
* Day 1: Ipilimumab 3 mg/kg
* Days 22: Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg
* Day 43: Nivolumab 3 mg/kg
* Day 56-84: Radical cystectomy or nefro/ureterectomy with appropriate lymph node dissection
Patients in cohort 2 (n=30) were randomized between cohort 2a and 2b
Cohort 2a (n=15):
* Day 1: Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg
* Days 22: Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg
* Day 43: Nivolumab 3 mg/kg
* Day 56-84: Radical cystectomy or nefro/ureterectomy with appropriate lymph node dissection
Cohort 2b (n=15):
* Day 1: Ipilimumab 1 mg/kg + Nivolumab 3 mg/kg
* Days 22: Ipilimumab 1 mg/kg + Nivolumab 3 mg/kg
* Day 43: Nivolumab 3 mg/kg
* Day 56-84: Radical cystectomy or nefro/ureterectomy with appropriate lymph node dissection
The primary endpoint for cohort 1 in this trial was safety. We determined the number of patients that had surgical resection \<12 weeks from first infusion, as this is an endpoint that is clinically meaningful for this population. After surgery, patients attended study visits at day 8 and day 29. Their final study visit for physical examination and laboratory testing is at day 57 (+/- 7 days), which is scheduled to anticipate late-onset adverse events (particularly endocrine). After this final visit, patients were followed according to standard clinical guidelines. Tumor biopsies/material preservation were required at baseline and during surgery.
In cohort 2, we randomized patients between 2 arms. Here, the main secondary outcomes were:
* To compare the efficacy of pre-operative ipilimumab + nivolumab in cohort 1 (sequenced ipilimumab/nivolumab), versus cohort 2a (ipi 3 mg/kg and nivo 1 mg/kg) and cohort 2b (ipi 1 mg/kg and nivo 3 mg/kg). Efficacy was defined as the pCR rate at resection.
* Provide an estimate of ≥grade 3 immune-related toxicity in the ipi3/nivo1 and ipi1/nivo3 cohorts as opposed to the initial cohort (Cohort 1)
An important additional secondary endpoint is translational. The main testable hypothesis is that a significant percentage of nonresponse can be explained by immune-inhibitory processes. Absence of immune infiltrates, presence of significant numbers of regulatory T-cells and presence of significant numbers of myeloid-derived suppressor cells will be compared between responders and nonresponders. The efficacy will be defined as the percentage of pathological complete response (pCR) at cystectomy (secondary endpoint).
* cT3-4aN0M0 OR
* T1-4aN1-3M0
Cohort 1 (n=24):
* Day 1: Ipilimumab 3 mg/kg
* Days 22: Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg
* Day 43: Nivolumab 3 mg/kg
* Day 56-84: Radical cystectomy or nefro/ureterectomy with appropriate lymph node dissection
Patients in cohort 2 (n=30) were randomized between cohort 2a and 2b
Cohort 2a (n=15):
* Day 1: Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg
* Days 22: Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg
* Day 43: Nivolumab 3 mg/kg
* Day 56-84: Radical cystectomy or nefro/ureterectomy with appropriate lymph node dissection
Cohort 2b (n=15):
* Day 1: Ipilimumab 1 mg/kg + Nivolumab 3 mg/kg
* Days 22: Ipilimumab 1 mg/kg + Nivolumab 3 mg/kg
* Day 43: Nivolumab 3 mg/kg
* Day 56-84: Radical cystectomy or nefro/ureterectomy with appropriate lymph node dissection
The primary endpoint for cohort 1 in this trial was safety. We determined the number of patients that had surgical resection \<12 weeks from first infusion, as this is an endpoint that is clinically meaningful for this population. After surgery, patients attended study visits at day 8 and day 29. Their final study visit for physical examination and laboratory testing is at day 57 (+/- 7 days), which is scheduled to anticipate late-onset adverse events (particularly endocrine). After this final visit, patients were followed according to standard clinical guidelines. Tumor biopsies/material preservation were required at baseline and during surgery.
In cohort 2, we randomized patients between 2 arms. Here, the main secondary outcomes were:
* To compare the efficacy of pre-operative ipilimumab + nivolumab in cohort 1 (sequenced ipilimumab/nivolumab), versus cohort 2a (ipi 3 mg/kg and nivo 1 mg/kg) and cohort 2b (ipi 1 mg/kg and nivo 3 mg/kg). Efficacy was defined as the pCR rate at resection.
* Provide an estimate of ≥grade 3 immune-related toxicity in the ipi3/nivo1 and ipi1/nivo3 cohorts as opposed to the initial cohort (Cohort 1)
An important additional secondary endpoint is translational. The main testable hypothesis is that a significant percentage of nonresponse can be explained by immune-inhibitory processes. Absence of immune infiltrates, presence of significant numbers of regulatory T-cells and presence of significant numbers of myeloid-derived suppressor cells will be compared between responders and nonresponders. The efficacy will be defined as the percentage of pathological complete response (pCR) at cystectomy (secondary endpoint).
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| CA209-9Y4 | OTHER | Bristol-Myers Squibb | View |