Metastatic or Locally Advanced Unresectable Urothelial Cancer MedDRA version: 21.1 Level: LLT Classification code 10077840 Term: Urothelial cancer of renal pelvis System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10046723 Term: Urothelial carcinoma ureter System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classificat
Conditions
Sponsors
Gilead Sciences Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Female or male subjects, = 18 years of age, able to understand and give written informed consent. 2) Subjects with histologically documented metastatic or locally advanced unresectable UC defined as: • Tumor (T) 4b, any node (N) or • Any T, N 2-3 Tumors of upper and lower urinary tract are permitted. Mixed histologic types are allowed if urothelial is the predominant histology. 3) ECOG PS score of 0 or 1. 4) Subjects with progression or recurrence following receipt of platinum-containing regimen and anti-PD-1/PD-L1 therapy for metastatic or locally advanced unresectable disease will be enrolled. a) Subjects with recurrence or progression = 12 months following completion of cisplatin-containing chemotherapy given in the neoadjuvant/ adjuvant setting may utilize that line of therapy to be eligible for the study. The 12-month period is counted from completion of surgical intervention or cisplatin therapy, respectively. These subjects must receive anti-PD-1/PD-L1 therapy in the metastatic or locally advanced unresectable setting to be eligible. b) Subjects who received either carboplatin or anti-PD-1/PD-L1 therapy in the neoadjuvant/ adjuvant setting will not be able to count that line of therapy towards eligibility for the study. c) Cisplatin-ineligible subjects who meet one of the below criteria and who were treated with carboplatin in the metastatic or locally advanced unresectable settings may count that line of therapy towards eligibility. They must then have received anti-PD-1/PDL1 therapy in metastatic or locally advanced unresectable setting to be eligible for the study. Cisplatin ineligibility is defined as meeting one of the following criteria: i) Creatinine Clearance 20 mg of prednisone (or equivalent) daily for brain metastases for at least 7 days prior to first dose of the study drug. 6) Adequate hematologic counts without transfusion or growth factor support within 2 weeks of study drug initiation (hemoglobin = 9 g/dL, absolute neutrophil count [ANC] = 1,500/mm3, and platelets = 100,000/µL). 7) Adequate hepatic function (bilirubin = 1.5x institutional upper limit of normal [IULN], aspartate aminotransferase [AST] and alanine aminotransferase [ALT] = 2.5 x IULN or = 5 x IULN if known liver metastases and serum albumin > 3 g/dL). Docetaxel
Exclusion criteria
Exclusion criteria: 1) Women who are pregnant or lactating. 2) Have had a prior anti-cancer mAb/ADC within 4 weeks prior to C1D1 or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to C1D1. Subjects participating in observational studies are eligible. 3) Have received prior chemotherapy for urothelial cancer with any available SOC therapies in the control arm (ie, either prior paclitaxel and docetaxel in countries where vinflunine is not an approved therapy, or either paclitaxel, docetaxel and vinflunine in countries where vinflunine is approved and is commercially available). 4) Have not recovered (ie, = Grade 1) from AEs due to previously administered chemotherapeutic agent. • Note: Subjects with = Grade 2 neuropathy or any grade of alopecia are an exception to this criterion and will qualify for the study. • Note: If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study therapy. 5) Have previously received topoisomerase 1 inhibitors. 6) Have an active second malignancy. • Note: Subjects with a history of malignancy that have been completely treated and with no evidence of active cancer for 3 years prior to enrollment, or subjects with surgically cured tumors with low risk of recurrence are allowed to enroll in the study after discussion with the medical monitor. 7) Have active cardiac disease, defined as: a) Myocardial infarction or unstable angina pectoris within 6 months of C1D1 b) History of serious ventricular arrhythmia (ie, 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 anti-arrhythmic medication); history of QT interval prolongation. c) NYHA Class III or greater congestive heart failure or left ventricular ejection fraction of <40%. 8) Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or GI perforation within 6 months of enrollment. 9) Have an active serious infection requiring anti-infective therapy (Contact medical monitor for clarification). 10) Have known history of Human Immunodeficiency Virus (HIV)-1/2 with undetectable viral load and on medications that may interfere with SN-38 metabolism. 11) Have active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). In subjects with a history of HBV or HCV, subjects with a detectable viral load 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. 13) Have inability to tolerate or are allergic to any potential TPC agent or sacituzumab govitecan or unable or unwilling to receive the doses specified in the protocol. 14) Have inability to complete all specified study procedures for any reason. 15) History of active interstitial lung disease or noninfectious pneumonitis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess Overall Survival with sacituzumab govitecan in comparison with treatment of physician’s choice (TPC) in subjects with metastatic or locally advanced unresectable UC.;Secondary Objective: 1. To assess PFS of sacituzumab govitecan in comparison with TPC by investigator assessment and blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 2. To assess ORR, clinical benefit rate (CBR), and duration of objective tumor response (DOR) with sacituzumab govitecan in comparison with TPC by investigator assessment and BICR using RECIST v1.1 3. To assess safety and tolerability of sacituzumab govitecan in comparison with TPC 4. To assess Quality of Life (QOL) with sacituzumab govitecan in comparison with TPC;Primary end point(s): Overall Survival (OS): OS is defined as the time from the date of randomization to the date of death, regardless of cause. If a subject is not known to have died, OS will be censored at the date the subject is last known to be alive.;Timepoint(s) of evaluation of this end point: Monitored throughout the study and OS will be captured q8 weeks once patients discontinue treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression-free Survival (PFS) by investigator assessment and Blinded Independent Central Review (BICR) using RECIST v1.1 2. Objective Response Rate (ORR), Clinical Benefit Rate (CBR) and Duration of Objective Tumor Response (DOR) by investigator assessment and BICR using RECIST v1.1 3. Safety and tolerability evaluated by AEs, SAEs, and laboratory changes 4. European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) score and European Quality of Life 5-dimensions 5-levels (EuroQOL EQ-5D-5L) score;Timepoint(s) of evaluation of this end point: Monitored throughout the study | — |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, China, Croatia, Czechia, Czech Republic, France, Georgia, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Korea, Republic of, Portugal, Russian Federation, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials Mailbox
Gilead Sciences Inc
Outcome results
None listed