NCT04527991已完成3 期
A Randomized Open-Label Phase III Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Subjects With Metastatic or Locally Advanced Unresectable Urothelial Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 711
- 试验地点
- 446
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The primary objective of this study is to assess overall survival (OS) with sacituzumab govitecan-hziy in comparison with treatment of physician's choice (TPC) in participants with metastatic or locally advanced unresectable urothelial cancer (UC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Individuals 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.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or
- •Individuals with progression or recurrence following receipt of platinum-containing regimen and anti programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) therapy for metastatic or locally advanced unresectable disease will be enrolled.
- •Individuals with recurrence or progression ≤12 months following completion of cisplatin-containing chemotherapy given in the neo-adjuvant/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 platinum therapy, respectively. These individuals must receive anti PD-1/PD-L1 therapy in the metastatic or locally advanced unresectable setting to be eligible.
- •Individuals who received either carboplatin or anti PD-1/PD-L1 therapy in the neo- adjuvant/adjuvant setting will not be able to count that line of therapy towards eligibility for the study.
- •Cisplatin ineligible individuals 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/PD-L1 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:
- •Creatinine Clearance < 60 mL/min
- •Grade ≥ 2 Audiometric Hearing Loss
- •Grade ≥ 2 Peripheral Neuropathy
- •New York Heart Association (NYHA) Class III heart failure
- •ECOG PS ≥ 2
- •Anti PD-1/PD-L1 therapy administered as part of maintenance therapy may be counted towards eligibility for the study
- •Individuals who have progressed after receiving enfortumab vedotin in prior lines of therapy, and individuals who are either ineligible or unable to tolerate enfortumab vedotin therapy, are eligible to enroll in the study
- •Individuals who received only concurrent chemoradiation for bladder preservation without further systemic therapy are not eligible to enroll in the study. The substitution of carboplatin for cisplatin does not constitute a new regimen provided no new chemotherapeutic agents were added to the regimen and no progression was noted prior to the change in platinum.
- •Individuals with previously treated brain metastases may participate in the study provided they have stable central nervous system disease for at least 4 weeks prior to the first dose of study drug and stabilization of all neurologic symptoms, have no evidence of new or enlarging brain metastases, and are not using steroids >20 mg of prednisone (or equivalent) daily for brain metastases for at least 7 days prior to first dose of the study drug.
- •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/mm^3, and platelets ≥100,000/µL).
- •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 will only be option in TPC arm for individuals with a total bilirubin ≤1 x IULN, and an AST and/or ALT ≤1.5x IULN if alkaline phosphatase is also >2.5 x IULN.
- •Creatinine clearance ≥30 mL/min as assessed by the Cockcroft-Gault equation or other validated instruments (e.g. Modification of Diet in Renal Disease (MDRD) equation).
- •Females of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study drug. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- •Females of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study drug. Individuals of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >2 years.
- •Males must agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy.
排除标准
- •Females who are pregnant or lactating.
- •Have had a prior anti-cancer monoclonal antibody (mAb)/ antibody-drug conjugate (ADC) within 4 weeks prior to Cycle 1 Day 1 (C1D1) or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to C1D
- •Individuals participating in observational studies are eligible.
- •Have received prior chemotherapy for UC with any available standard of care (SOC) therapies in the control arm (i.e., both prior paclitaxel and docetaxel in regions where vinflunine is not an approved therapy, or prior paclitaxel, docetaxel and vinflunine in regions where vinflunine is approved and is commercially available).
- •Have not recovered (i.e., ≤ Grade 1) from adverse events due to previously administered chemotherapeutic agent.
- •Note: Individuals with ≤ Grade 2 neuropathy or any grade of alopecia are an exception to this criterion and will qualify for the study.
- •Note: If Individuals received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study therapy.
- •Have previously received topoisomerase 1 inhibitors.
- •Have an active second malignancy.
- •Note: Individuals with a history of malignancy that have been completely treated and with no evidence of active cancer for 3 years prior to enrollment, or individuals with surgically cured tumors with low risk of recurrence are allowed to enroll in the study after discussion with the medical monitor.
- •Have active cardiac disease, defined as:
- •Myocardial infarction or unstable angina pectoris within 6 months of C1D
- •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%.
- •Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal (GI) perforation within 6 months of enrollment.
- •Have an active serious infection requiring anti-infective therapy (Contact medical monitor for clarification).
- •Have known history of Human Immunodeficiency Virus (HIV)-1/2 with undetectable viral load and on medications that may interfere with SN-38 metabolism.
- •Have active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). In individuals with a history of HBV or HCV, individuals with a detectable viral load will be excluded.
- •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.
- •Have inability to tolerate or are allergic to any potential TPC agent or sacituzumab govitecan-hziy or unable or unwilling to receive the doses specified in the protocol.
- •Have inability to complete all specified study procedures for any reason.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Treatment of Physician's Choice
Active Comparator
Participants will receive 1 of 3 standard-of-care chemotherapeutic options, as determined by the investigator prior to randomization, and will continue to receive the same treatment for the duration of the study until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion is met.
Paclitaxel 175 mg/m^2 IV on Day 1 of every 21-day cycle or Docetaxel 75 mg/m^2 IV on Day 1 of every 21-day cycle or Vinflunine 320 mg/m^2 IV on Day 1 of every 21-day cycle (in countries where vinflunine was approved and was commercially available).
干预措施: Paclitaxel (Drug)
Treatment of Physician's Choice
Active Comparator
Participants will receive 1 of 3 standard-of-care chemotherapeutic options, as determined by the investigator prior to randomization, and will continue to receive the same treatment for the duration of the study until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion is met.
Paclitaxel 175 mg/m^2 IV on Day 1 of every 21-day cycle or Docetaxel 75 mg/m^2 IV on Day 1 of every 21-day cycle or Vinflunine 320 mg/m^2 IV on Day 1 of every 21-day cycle (in countries where vinflunine was approved and was commercially available).
干预措施: Docetaxel (Drug)
Treatment of Physician's Choice
Active Comparator
Participants will receive 1 of 3 standard-of-care chemotherapeutic options, as determined by the investigator prior to randomization, and will continue to receive the same treatment for the duration of the study until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion is met.
Paclitaxel 175 mg/m^2 IV on Day 1 of every 21-day cycle or Docetaxel 75 mg/m^2 IV on Day 1 of every 21-day cycle or Vinflunine 320 mg/m^2 IV on Day 1 of every 21-day cycle (in countries where vinflunine was approved and was commercially available).
干预措施: Vinflunine (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to 3.5 years
OS is defined as time from the date of randomization to the date of death, regardless of cause.
次要结局
- Progression-Free Survival (PFS) by Investigator Assessment(Up to 3.5 years)
- European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Score(Up to 3.5 years)
- Duration of Objective Tumor Response (DOR) by BICR(Up to 3.5 years)
- Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities(Up to 3.5 years)
- Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR)(Up to 3.5 years)
- Objective Response Rate (ORR) by Investigator Assessment(Up to 3.5 years)
- European Quality of Life 5-Dimensions 5 Levels Instrument (EuroQOL EQ-5D-5L) Score(Up to 3.5 years)
- Clinical Benefit Rate (CBR) by BICR(Up to 3.5 years)
- Percentage of Participants Experiencing any Serious Treatment Emergent Adverse Events(Up to 3.5 years)
- Objective Response Rate (ORR) by BICR(Up to 3.5 years)
- Clinical Benefit Rate (CBR) by Investigator Assessment(Up to 3.5 years)
- Duration of Objective Tumor Response (DOR) by Investigator Assessment(Up to 3.5 years)
- Percentage of Participants Experiencing any Treatment Emergent Adverse Events(Up to 3.5 years)
研究者
研究点 (446)
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