Back to resultsPembrolizumab-Sacituzumab Govitecan Combination to Treat High-risk, Localized Bladder Cancer (SURE-02)
Primary Purpose
Muscle-invasive Urothelial Carcinoma of the Bladder
Status
Recruiting
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA]
Sponsored by
About this trial
This is an interventional treatment trial for Muscle-invasive Urothelial Carcinoma of the Bladder
Eligibility Criteria
Inclusion Criteria:
- written informed consent
- >18 years of age
- Histopathologically confirmed urothelial carcinoma.
- Fit and planned for RC ECOG performance status score of 0 or 1
- Adequate hematologic counts , hepatic and renal function.
- Negative pregnancy test and Effective contraception during the study, unless evidence of infertility exists
- Clinical stage T2-T4aN0M0 MIBC, assessed by CT + PET/CT + mpMRI.
- Ineligibility to receive cisplatin-based neoadjuvant chemotherapy based on Galsky's criteria OR refusal to receive neoadjuvant cisplatin-based chemotherapy
Exclusion Criteria:
- prior systemic anti-cancer therapy including investigational agents and immunotherapy,
- prior radiotherapy on the bladder tumor, partial cystectomy.
- Refusal to undergo RC.live vaccine, antibiotics within 30 days prior to the first dose of study drug.
- Participation in a study of an investigational agent or device, additional known malignancy , severe hypersensitivity to study drugs and/or any of their excipients, active autoimmune disease that required systemic treatment.
- history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- active chronic inflammatory bowel disease, any condition that is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- active cardiac disease, defined as: A) Myocardial infarction or unstable angina pectoris within 6 months of C1D1 B) History of serious ventricular arrhythmia, high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications; history of QT interval prolongation C) NYHA Class III or greater congestive heart failure or left ventricular ejection fraction of < 40%
- known history of HIV-1/2 infection,
- known history of Hepatitis B
- active Hepatitis C virus infection.
- other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
- High dose systemic corticosteroids are not allowed within 2 weeks of C1D1.
- Have received or are currently receiving (within the previous 2 weeks) antibiotics.
Sites / Locations
- Fondazione San RaffaeleRecruiting
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Single Arm
Arm Description
Single Arm treatment
Outcomes
Primary Outcome Measures
Number of complete pathological responses, defined as the absence of viable tumor cells on the histological examination of the cystectomy
Number of complete pathological responses, defined as the absence of viable tumor cells on the histological examination of the cystectomy
Secondary Outcome Measures
To evaluate the proportion of patients who will be pathologically downstaged to ypT minor or equal to 1N0M0.
To evaluate the proportion of patients who will be pathologically downstaged to ypT minor or equal to 1N0M0.
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.
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.
To evaluate the surgical and medical safety of neoadjuvant combination therapy, as well as of the adjuvant pembrolizumab therapy.
To evaluate the surgical and medical safety of neoadjuvant combination therapy, as well as of the adjuvant pembrolizumab therapy.
To assess survival outcomes (event-free survival and overall survival), in the total population and in the subgroups according to the pathological response.
To assess survival outcomes (event-free survival and overall survival), in the total population and in the subgroups according to the pathological response.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05535218
Brief Title
Pembrolizumab-Sacituzumab Govitecan Combination to Treat High-risk, Localized Bladder Cancer
Acronym
SURE-02
Official Title
An Open Label, Single-arm, Phase 2 Study of Perioperative Pembrolizumab Plus Sacituzumab Govitecan for Patients With Muscle-invasive Bladder Cancer Who Cannot Receive or Refuse Cisplatin-based Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 15, 2022 (Actual)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
September 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Claudia Guerrieri
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a perioperative Phase 2, open-label, non-randomized, single-cohort study in patients with urothelial carcinoma of the bladder who cannot receive or refuse to receive cisplatin-based chemotherapy.
Detailed Description
A transurethral resection of the bladder tumor (TURBT) for biopsy, histological characterization, and local staging will be executed first, according to the guidelines.
Eligible patients will receive neoadjuvant treatment: 10 mg/kg sacituzumab govitecan IV, on days 1, 8, of each 21 day cycle.
Pembrolizumab will be administered in combination with sacituzumab on day 1, every 21 days, at the standard dose of 200 mg intravenously.
A total of 4 cycles is planned before surgery. Surgery will be planned at the time of study inclusion to be done ideally within 4 weeks of the last dose of study drug, and not later than 12 weeks from the last dose of study drug.
After surgery patients will receive additional 13 cycles of pembrolizumab at the standard dose, every 3 weeks, accounting for a total of 17 cycles of perioperative pembrolizumab (neoadjuvant + adjuvant). Imaging assessments post-cystectomy will be managed according to the current EAU guidelines.
At the end of the adjuvant period, patients will enter the follow-up period which will last until 12 months from the last dose of pembrolizumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscle-invasive Urothelial Carcinoma of the Bladder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Single Arm
Arm Type
Other
Arm Description
Single Arm treatment
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA]
Other Intervention Name(s)
sacituzumab-govitecan
Intervention Description
Neoadjuvant treatment: 10 mg/kg sacituzumab-govitecan IV, on days 1, 8, of each 21 day cycle; Pembrolizumab will be administered in combination with sacituzumab-govitecan on day 1, every 21 days, at the standard dose of 200 mg intravenously. A total of 4 cycles is planned before surgery.
After surgery patients will receive additional 13 cycles of pembrolizumab at the standard dose, every 3 weeks, accounting for a total of 17 cycles of perioperative pembrolizumab (neoadjuvant + adjuvant).
Primary Outcome Measure Information:
Title
Number of complete pathological responses, defined as the absence of viable tumor cells on the histological examination of the cystectomy
Description
Number of complete pathological responses, defined as the absence of viable tumor cells on the histological examination of the cystectomy
Time Frame
Upon completion of the study up to 40 months
Secondary Outcome Measure Information:
Title
To evaluate the proportion of patients who will be pathologically downstaged to ypT minor or equal to 1N0M0.
Description
To evaluate the proportion of patients who will be pathologically downstaged to ypT minor or equal to 1N0M0.
Time Frame
Upon completion of the study up to 40 months
Title
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.
Description
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.
Time Frame
up to 16 months
Title
To evaluate the surgical and medical safety of neoadjuvant combination therapy, as well as of the adjuvant pembrolizumab therapy.
Description
To evaluate the surgical and medical safety of neoadjuvant combination therapy, as well as of the adjuvant pembrolizumab therapy.
Time Frame
Up to 6 months
Title
To assess survival outcomes (event-free survival and overall survival), in the total population and in the subgroups according to the pathological response.
Description
To assess survival outcomes (event-free survival and overall survival), in the total population and in the subgroups according to the pathological response.
Time Frame
Up to 40 months
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
written informed consent
>18 years of age
Histopathologically confirmed urothelial carcinoma.
Fit and planned for RC ECOG performance status score of 0 or 1
Adequate hematologic counts , hepatic and renal function.
Negative pregnancy test and Effective contraception during the study, unless evidence of infertility exists
Clinical stage T2-T4aN0M0 MIBC, assessed by CT + PET/CT + mpMRI.
Ineligibility to receive cisplatin-based neoadjuvant chemotherapy based on Galsky's criteria OR refusal to receive neoadjuvant cisplatin-based chemotherapy
Exclusion Criteria:
prior systemic anti-cancer therapy including investigational agents and immunotherapy,
prior radiotherapy on the bladder tumor, partial cystectomy.
Refusal to undergo RC.live vaccine, antibiotics within 30 days prior to the first dose of study drug.
Participation in a study of an investigational agent or device, additional known malignancy , severe hypersensitivity to study drugs and/or any of their excipients, active autoimmune disease that required systemic treatment.
history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
active chronic inflammatory bowel disease, any condition that is not in the best interest of the subject to participate, in the opinion of the treating investigator.
active cardiac disease, defined as: A) Myocardial infarction or unstable angina pectoris within 6 months of C1D1 B) History of serious ventricular arrhythmia, high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications; history of QT interval prolongation C) NYHA Class III or greater congestive heart failure or left ventricular ejection fraction of < 40%
known history of HIV-1/2 infection,
known history of Hepatitis B
active Hepatitis C virus infection.
other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
High dose systemic corticosteroids are not allowed within 2 weeks of C1D1.
Have received or are currently receiving (within the previous 2 weeks) antibiotics.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea Necchi
Phone
00390226435789
Email
necchi.andrea@hsr.it
Facility Information:
Facility Name
Fondazione San Raffaele
City
Milan
State/Province
MI
ZIP/Postal Code
20132
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Necchi
First Name & Middle Initial & Last Name & Degree
Andrea Necchi
12. IPD Sharing Statement
Plan to Share IPD
No
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Pembrolizumab-Sacituzumab Govitecan Combination to Treat High-risk, Localized Bladder Cancer
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