Ignite Creation Date:
2024-10-26 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06528483
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-19
Brief Title:
Bladder Preservation With Sacituzumab Govitecan Zimberelimab for Muscle-Invasive Bladder Cancer
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Bladder Preservation With Sacituzumab Govitecan Zimberelimab for Muscle-Invasive Bladder Cancer in Cisplatin-unfit and Unwilling for Cystectomy Patients Phase II Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
preSAVE
Brief Summary:
Patients with MIBC N0N1 unwilling or unfit for cystectomy will receive SG Zimberelimab for 3 cycles of treatment prior of first radiological and TURB re-evaluation
Patients with stable disease or downstaging will continue Zimberelimab up to 1 year The goal of this trial is to demonstate that Sacituzumab Govitecan Zimberelimab can avoid cistectomy and can prolong or avoid recurrence to metastatic disease in selected patients with muscle-invasive bladder cancer
The primary endpoint of this trial is Event Free Survival that is defined as clinical evidence of new or progressing nodal or any distant metastatic disease radical cystectomy or death due to any cause from date of inclusion to the first documentation of a EFS event
Patients with stable disease or downstaging will continue Zimberelimab up to 1 year The goal of this trial is to demonstate that Sacituzumab Govitecan Zimberelimab can avoid cistectomy and can prolong or avoid recurrence to metastatic disease in selected patients with muscle-invasive bladder cancer
The primary endpoint of this trial is Event Free Survival that is defined as clinical evidence of new or progressing nodal or any distant metastatic disease radical cystectomy or death due to any cause from date of inclusion to the first documentation of a EFS event
Detailed Description:
This is an open-label multi-center single-group phase 2 study Patients with MIBC N0N1 unwilling or unfit for cystectomy will receive SG Zimberelimab for 3 cycles of treatment prior of first radiological and TURB re-evaluation
Approximately 63 patients will be enrolled and assigned to study intervention At screening a tumor specimen from TURBT or biopsy done as early as 90 days prior to enrollment will be submitted for central pathology review All participants will undergo baseline screening imaging CT or MRI of the chest abdomen pelvis for clinical staging
Eligible participants will be allocated to study intervention which consist in SG Zimberelimab for 3 cycles followed by Zimberelimab for 13 cycles in patients who achieve CRPRSD at tumor evaluation
The planned total duration of treatment is approximately 1 year 3 cycles of SG and 16 cycles of Zimberelimab
Treatment will be discontinued if the participant experiences unacceptable AEs intercurrent illness that prevents further administration of treatment the investigators decision to withdraw the participant the participant withdraws consent pregnancy of the participant noncompliance with study intervention or procedure requirements or the maximum number of cycles has been received for each treatment component individually
Participants will complete 3 cycles of induction study intervention followed by repeat imaging studies same modality as screening within 4 weeks 21 days - 7 days after C3D21 to exclude disease progression mpMRIcontrast-enhanced or CT scan will assess local invasion by T3 disease or higher and the radiological response to treatment
Participants who remain radiographically free of distant metastases and PRSDCR RECIST v11 will proceed to TURBT within 6 weeks of the last dose of SG TURBT will enable histopathological re-staging and will evaluate pathological response to treatment The inclusion of bladder muscle in the resection specimen is required Cystoscopy will be performed before TURBT as indicated in the Schedule of Activities
Patients with no evidence of disease at the cystoscopy will undergo bladder mapping in case of positive urine cytology In case of negative urine cytology patients will be considered in as complete respose in case of no evidence of disease at radiological evaluation
Participants with radiological progression to metastatic disease or locally advanced disease from cT2 to cT4 or from N0 to N1 as assessed radiographically at this time will be considered to have met the primary endpoint of EFS ie had an event and will not receive further therapy on study but will transition into survival follow-up and will be treated as per clinical practice
Participants with pathological downstaging and radiological complete or partial response will continue to receive zimberelimab for 13 cycles 16 cycles as a total to complete approximately 1 year of total therapy
Non-responder patients who will maintain radiological or pathological stability will choose to undergo RC or RTCT or to continue Zimberelimab for 1 years Additional TURBT could be performed in order to achieve local control according to the centre clinical practice
Response to study intervention will be assessed through TURBT and CT SCAN andor MRI Imaging should continue to be performed until an EFS event occurs or withdrawal of consent whichever occurs first If new anticancer therapy is initiated this should be documented
All subjects will be followed for OS every 3 months until death lost to follow-up or withdrawal of study consent Additional survival follow-up may continue for up to 3-5 years from the time of this analysis To evaluate metastasis free survival subjects will be monitored by radiographic assessment and cystoscopy on an every-12-week schedule 5 days RECIST 11 criteria will be used for the assessment Subjects will be evaluated at every SG Zimberelimab dose administration plus two additional follow-up visits for safety within the first 100 days from the last dose of study therapy Beyond 100 days from the last dose of study therapy subjects will be followed for ongoing drug-related adverse events until resolved return to baseline or deemed irreversible or until lost to follow-up or withdrawal of study consent
To assess local recurrence cystoscopy will be performed every 12 weeks - 1 7 days In case of local recurrence patients could be managed with TURBT as per clinical practice in case patients will still be unfit for cystectomy or refuse surgery
Approximately 63 patients will be enrolled and assigned to study intervention At screening a tumor specimen from TURBT or biopsy done as early as 90 days prior to enrollment will be submitted for central pathology review All participants will undergo baseline screening imaging CT or MRI of the chest abdomen pelvis for clinical staging
Eligible participants will be allocated to study intervention which consist in SG Zimberelimab for 3 cycles followed by Zimberelimab for 13 cycles in patients who achieve CRPRSD at tumor evaluation
The planned total duration of treatment is approximately 1 year 3 cycles of SG and 16 cycles of Zimberelimab
Treatment will be discontinued if the participant experiences unacceptable AEs intercurrent illness that prevents further administration of treatment the investigators decision to withdraw the participant the participant withdraws consent pregnancy of the participant noncompliance with study intervention or procedure requirements or the maximum number of cycles has been received for each treatment component individually
Participants will complete 3 cycles of induction study intervention followed by repeat imaging studies same modality as screening within 4 weeks 21 days - 7 days after C3D21 to exclude disease progression mpMRIcontrast-enhanced or CT scan will assess local invasion by T3 disease or higher and the radiological response to treatment
Participants who remain radiographically free of distant metastases and PRSDCR RECIST v11 will proceed to TURBT within 6 weeks of the last dose of SG TURBT will enable histopathological re-staging and will evaluate pathological response to treatment The inclusion of bladder muscle in the resection specimen is required Cystoscopy will be performed before TURBT as indicated in the Schedule of Activities
Patients with no evidence of disease at the cystoscopy will undergo bladder mapping in case of positive urine cytology In case of negative urine cytology patients will be considered in as complete respose in case of no evidence of disease at radiological evaluation
Participants with radiological progression to metastatic disease or locally advanced disease from cT2 to cT4 or from N0 to N1 as assessed radiographically at this time will be considered to have met the primary endpoint of EFS ie had an event and will not receive further therapy on study but will transition into survival follow-up and will be treated as per clinical practice
Participants with pathological downstaging and radiological complete or partial response will continue to receive zimberelimab for 13 cycles 16 cycles as a total to complete approximately 1 year of total therapy
Non-responder patients who will maintain radiological or pathological stability will choose to undergo RC or RTCT or to continue Zimberelimab for 1 years Additional TURBT could be performed in order to achieve local control according to the centre clinical practice
Response to study intervention will be assessed through TURBT and CT SCAN andor MRI Imaging should continue to be performed until an EFS event occurs or withdrawal of consent whichever occurs first If new anticancer therapy is initiated this should be documented
All subjects will be followed for OS every 3 months until death lost to follow-up or withdrawal of study consent Additional survival follow-up may continue for up to 3-5 years from the time of this analysis To evaluate metastasis free survival subjects will be monitored by radiographic assessment and cystoscopy on an every-12-week schedule 5 days RECIST 11 criteria will be used for the assessment Subjects will be evaluated at every SG Zimberelimab dose administration plus two additional follow-up visits for safety within the first 100 days from the last dose of study therapy Beyond 100 days from the last dose of study therapy subjects will be followed for ongoing drug-related adverse events until resolved return to baseline or deemed irreversible or until lost to follow-up or withdrawal of study consent
To assess local recurrence cystoscopy will be performed every 12 weeks - 1 7 days In case of local recurrence patients could be managed with TURBT as per clinical practice in case patients will still be unfit for cystectomy or refuse surgery
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None