Ignite Creation Date:
2024-10-26 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06537154
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-29
Brief Title:
NEO-BLAST Neoadjuvant Therapy for Bladder Cancer Followed by Active Surveillance vs Treatment
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Active Surveillance Versus Definitive Local Therapy for Patients Showing Clinical Complete Response Following Neoadjuvant Therapy for Muscle Invasive Bladder Cancer
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
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:
NEO-BLAST
Brief Summary:
Invasive bladder cancer is managed with neoadjuvant therapy followed by bladder removal cystectomy Research shows that approximately 40 of patient will have no remaining cancer left in their bladder after completion of the initial systemic treatment and perhaps could have avoided the surgery However currently physicians lack the ability to identify these patients
The investigators believe that by using advanced imaging MRI bladder biopsies and novel biomarkers that detect tumor DNA in blood and urine they can better identify participants without any remaining cancer after chemotherapy This will make active surveillance of these participants safer In this study participants without evidence of residual cancer will be randomized to active surveillance vs conventional bladder treatment bladder removal or chemo-radiation of the bladder This study will be a pilot randomized control trial RCT and if successful it will transition to a larger phase 3 RCT
The investigators believe that by using advanced imaging MRI bladder biopsies and novel biomarkers that detect tumor DNA in blood and urine they can better identify participants without any remaining cancer after chemotherapy This will make active surveillance of these participants safer In this study participants without evidence of residual cancer will be randomized to active surveillance vs conventional bladder treatment bladder removal or chemo-radiation of the bladder This study will be a pilot randomized control trial RCT and if successful it will transition to a larger phase 3 RCT
Detailed Description:
Purpose To assess the feasibility to randomize patients with muscle-invasive bladder cancer MIBC who experience a complete clinical response cCR following neoadjuvant therapy NAT as defined by negative ctDNA negative utDNA negative bladder MRI and negative repeat TURBT to active surveillance vs standard of care SOC with definitive bladder treatment
Hypothesis The hypothesize is that the combination of bladder re-staging with MRI repeat biopsy and the use of ctDNA and utDNA will markedly enhance the ability to identified participant who achieve an excellent response to NAT cCR and who could safely be offered AS
Justification
Cisplatin-based neoadjuvant therapy NAT followed by radical cystectomy RC or alternatively in selected patient a combination of chemo-radiation trimodal therapy TMT are the current standards of care for treatment of MIBC However both have significant potential toxicity that can impact quality of life Clinical trials have demonstrated that up to 38 of patients have a pathologic complete response pCR to NAT Those patients could potentially avoid RC or TMT Unfortunately the clinical tools to predict pCR are still considered inadequate and definitive local therapy is advised Retrospective data and now prospective phase 2 trials have reported promising outcomes in selected patients undergoing active surveillance A prospective randomized trial is still lacking to ensure non-inferiority of active surveillance over the standard of care
Primary Objectives
Phase 2 pilot RCT To determine the feasibility of randomizing patients with MIBC who experience a complete clinical response cCR following neoadjuvant treatment as defined by negative ctDNA negative utDNA negative bladder MRI and negative repeat TURBT to active surveillance AS or definitive bladder treatment DBT consisting of radical cystectomy RC or trimodal therapy TMT
Phase 3 To estimate the metastasis-free survival rate at 2 years among patients with MIBC who experience a complete clinical response cCR following NAT as defined by negative ctDNA negative utDNA negative bladder MRI and negative repeat TURBT and who are managed with active surveillance
Research design
Multi-center phase IIIII open label randomized clinical trial
After enrolment participants will received SOC NAT Blood and urine specimens will be collected before or at cycle 1 day 1 of NAT Participants will undergo conventional restaging during NAT recommended to be done at the end of cycle 2 Conventional imaging consists of computerized tomography CT scan of chestabdomenpelvis to rule-out local or distant progression on treatment Participants who have successfully completed the full regimen of SOC NAT and have not been found to have progression andor metastasis on their SOC CT scan will then undergo the following intervention for the clinical restaging CRS must be completed within 4 weeks after last dose of NAT
ctDNA and utDNA from blood and urine samples collected before and after completion of NAT
Restaging bladder MRI
Urine Cytology and Cystoscopy with template bladder biopsy under anesthesia with or without site-directed bladder biopsies
Definition of clinical complete response cCR
Absence of metastasis on conventional imaging
Negative MRI completed within 4 weeks of last dose of systemic treatment showing absence of VI-RADS 3 4 or 5 lesion
Transurethral bladder tumor resection TURBT with or without site-directed bladder biopsies showing absence of high-grade carcinoma cT1 andor extensive and multifocal CIS Focal CIS andor completely resected Ta will be included in the definition of cCR and offered randomization
Negative ctDNA
Negative utDNA
Participants with cCR will then be randomized to either active surveillance or definitive bladder treatment DBT RC or TMT according to patientphysician choice Participants who do not meet all criteria of cCR will proceed with SOC and have RC or TMT under the treating investigators care
Participants on active surveillance will adhere to the following schedule of activity
Cystoscopy with urine cytology every 3 months for 2 years After 2 years follow up schedule is at the discretion of the treating physician
Repeat chest-abdomen-pelvis imaging with CTMRI at 3 6 12 18 and 24 months After 2 years follow up schedule is at the discretion of the treating physician
Hypothesis The hypothesize is that the combination of bladder re-staging with MRI repeat biopsy and the use of ctDNA and utDNA will markedly enhance the ability to identified participant who achieve an excellent response to NAT cCR and who could safely be offered AS
Justification
Cisplatin-based neoadjuvant therapy NAT followed by radical cystectomy RC or alternatively in selected patient a combination of chemo-radiation trimodal therapy TMT are the current standards of care for treatment of MIBC However both have significant potential toxicity that can impact quality of life Clinical trials have demonstrated that up to 38 of patients have a pathologic complete response pCR to NAT Those patients could potentially avoid RC or TMT Unfortunately the clinical tools to predict pCR are still considered inadequate and definitive local therapy is advised Retrospective data and now prospective phase 2 trials have reported promising outcomes in selected patients undergoing active surveillance A prospective randomized trial is still lacking to ensure non-inferiority of active surveillance over the standard of care
Primary Objectives
Phase 2 pilot RCT To determine the feasibility of randomizing patients with MIBC who experience a complete clinical response cCR following neoadjuvant treatment as defined by negative ctDNA negative utDNA negative bladder MRI and negative repeat TURBT to active surveillance AS or definitive bladder treatment DBT consisting of radical cystectomy RC or trimodal therapy TMT
Phase 3 To estimate the metastasis-free survival rate at 2 years among patients with MIBC who experience a complete clinical response cCR following NAT as defined by negative ctDNA negative utDNA negative bladder MRI and negative repeat TURBT and who are managed with active surveillance
Research design
Multi-center phase IIIII open label randomized clinical trial
After enrolment participants will received SOC NAT Blood and urine specimens will be collected before or at cycle 1 day 1 of NAT Participants will undergo conventional restaging during NAT recommended to be done at the end of cycle 2 Conventional imaging consists of computerized tomography CT scan of chestabdomenpelvis to rule-out local or distant progression on treatment Participants who have successfully completed the full regimen of SOC NAT and have not been found to have progression andor metastasis on their SOC CT scan will then undergo the following intervention for the clinical restaging CRS must be completed within 4 weeks after last dose of NAT
ctDNA and utDNA from blood and urine samples collected before and after completion of NAT
Restaging bladder MRI
Urine Cytology and Cystoscopy with template bladder biopsy under anesthesia with or without site-directed bladder biopsies
Definition of clinical complete response cCR
Absence of metastasis on conventional imaging
Negative MRI completed within 4 weeks of last dose of systemic treatment showing absence of VI-RADS 3 4 or 5 lesion
Transurethral bladder tumor resection TURBT with or without site-directed bladder biopsies showing absence of high-grade carcinoma cT1 andor extensive and multifocal CIS Focal CIS andor completely resected Ta will be included in the definition of cCR and offered randomization
Negative ctDNA
Negative utDNA
Participants with cCR will then be randomized to either active surveillance or definitive bladder treatment DBT RC or TMT according to patientphysician choice Participants who do not meet all criteria of cCR will proceed with SOC and have RC or TMT under the treating investigators care
Participants on active surveillance will adhere to the following schedule of activity
Cystoscopy with urine cytology every 3 months for 2 years After 2 years follow up schedule is at the discretion of the treating physician
Repeat chest-abdomen-pelvis imaging with CTMRI at 3 6 12 18 and 24 months After 2 years follow up schedule is at the discretion of the treating physician
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