Muscle-invasive bladder cancer MedDRA version: 21.0 Level: LLT Classification code 10007293 Term: Carcinoma bladder System Organ Class: 100000004864
Conditions
Interventions
Product Name: sacituzumab govitecan
Product Code: [IMMU-132]
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: sacituzumab govitecan
CAS Number: 1491917-83-9
Current Spo
Sponsors
OSPEDALE SAN RAFFAELE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ¿ Female or male subjects, >18 years of age, able to understand and give written informed consent ¿ Histopathologically confirmed urothelial carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) transitional cell pattern. ¿ Fit and planned for RC (according to local guidelines). ¿ ECOG performance status score of 0 or 1 ¿ Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation (Hemoglobin = 9 g/dL, ANC = 1,500/ mm3, and Platelets = 100,000/ µL) ¿ Adequate hepatic function (Bilirubin = 1.5 IULN, AST and ALT = 2.5 x IULN or = 5 x IULN if known liver metastases and serum albumin >3 g/dl) ¿ Creatinine clearance =30 mL/min as assessed by the Cockcroft-Gault equation ¿ Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication, and must not be lactating. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required ¿ Female subjects of childbearing potential must be willing to use 2 methods of birthcontrol or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >2 years ¿ Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of study therapy. ¿ Clinical stage defining clinical T2-T4N0M0 disease by CT (or MRI) + PET/CT (within 4 weeks of randomization by RECIST v1.1). ¿ The patient accepts to undergo radical cystectomy. ¿ Ineligibility to receive cisplatin-based neoadjuvant chemotherapy based on Galsky’s criteria OR refusal to receive neoadjuvant cisplatin-based chemotherapy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 38 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: 1. Has received prior systemic anti-cancer therapy including investigational agents and immunotherapy. 2. Has received prior radiotherapy on the bladder tumor. 3. Refusal to undergo RC. 4. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. 5. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. 6. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Participants with low-risk early stage prostate cancer defined as follows are not excluded; Stage T1c or T2a with a Gleason score = 6 and prostatic-specific antigen (PSA) < 10 ng/mL either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation.Women who are pregnant or lactating 7. Has severe hypersensitivity (=Grade 3) to sacituzumab govitecan and/or any of its excipients. 8. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 9. Have active cardiac disease, defined as: • Myocardial infarction or unstable angina pectoris within 6 months of C1D1 • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation • NYHA Class III or greater congestive heart failure or left ventricular ejection fraction of < 40% 10. Have known history of HIV-1/2 with uncontrolled viral load. 11. Have active HBV or HCV. In subjects with a history of HBV or HCV, subjects with detectable viral loads will be excluded. 12. Have 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Number of complete pathological responses, defined as the absence of viable tumor cells on the histological examination of the cystectomy. Evidence of carcinoma in situ or non-muscle infiltrating disease does not define a complete pathological response.;Timepoint(s) of evaluation of this end point: At cistectomy, about 4 months after inclusion;Main Objective: To assess whether sacituzumab govitecan results in pathological complete response (herein referred to as either “pT0” or “pCR”) in patients with MIBC who cannot receive or refuse cisplatin-based chemotherapy.;Secondary Objective: • To evaluate radiological response on those patients with measurable disease. • To evaluate the surgical and medical safety of neoadjuvant therapy. • To assess survival outcomes (event-free survival and overall survival). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Evaluation of safety and tolerability of the treatment: Number of patients who experienced adverse events. Type, frequency, severity and relationship to the treatment of the adverse events, evaluated according the Common Toxicity Criteria for adverse events (CTCAE) v 5.0. Progression free survival Overall survival;Timepoint(s) of evaluation of this end point: During the course of the study Follow up every 12 weeks after final treatment | — |
Countries
Italy
Contacts
Public ContactGenitourinary Medical Oncology
Ospedale San Raffaele
Outcome results
None listed