An International, Multi-Center, Open-Label, Randomized, Phase III Trial of Sacituzumab Govitecan Versus Treatment of Physician Choice in Patients With Metastatic Triple-Negative Breast Cancer Who Received at Least Two Prior Treatments
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 529
- 试验地点
- 178
- 主要终点
- Progression-Free Survival (PFS) by Independent Review Committee (IRC) Assessment in Brain Metastasis Negative (BM-ve) Population
研究概览
简要总结
The primary objective of this study is to compare the efficacy of sacituzumab govitecan to the treatment of physician's choice (TPC) as measured by independently-reviewed Independent Review Committee (IRC) progression-free survival (PFS) in participants with locally advanced or metastatic triple-negative breast cancer (TNBC) previously treated with at least two systemic chemotherapy regimens for unresectable, locally advanced or metastatic disease, and without brain metastasis at baseline.
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
- •Histologically or cytologically confirmed TNBC based on the most recent analyzed biopsy or other pathology specimen. Triple negative is defined as <1% expression for estrogen receptor (ER) and progesterone receptor (PR) and negative for human epidermal growth factor receptor 2 (HER2) by in-situ hybridization.
- •Refractory to or relapsed after at least two prior standard therapeutic regimens for advanced/metastatic TNBC.
- •Prior exposure to a taxane in localized or advanced/metastatic setting.
- •Eligible for one of the chemotherapy options listed as TPC (eribulin, capecitabine, gemcitabine, or vinorelbine) as per investigator assessment.
- •Eastern Cooperative Oncology Group (ECOG) performance score of 0 or
- •Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Bone-only disease is not permitted.
- •At least 2 weeks beyond prior anti-cancer treatment (chemotherapy, endocrine therapy, radiotherapy, and/or major surgery), and recovered from all acute toxicities to Grade 1 or less (except alopecia and peripheral neuropathy).
- •At least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids < 20 mg prednisone or equivalent daily are permitted provided the dose is stable for 4 weeks).
- •Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, absolute neutrophil count (ANC) > 1,500 per mm^3, platelets > 100,000 per mm^3).
- •Adequate renal and hepatic function (creatinine clearance [CrCL] > 60 mL/min, bilirubin ≤ 1.5 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).
- •Recovered from all toxicities to Grade 1 or less by National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) v4.03 (except alopecia or peripheral neuropathy that may be Grade 2 or less) at the time of randomization. Participants with Grade 2 neuropathy are eligible but may not receive vinorelbine as TPC.
- •Participants with treated, non-progressive brain metastases, off high-dose steroids (>20 mg prednisone or equivalent) for at least 4 weeks can be enrolled in the trial.
排除标准
- •Women who are pregnant or lactating.
- •Women of childbearing potential or fertile men unwilling to use effective contraception during study and up to three months after treatment discontinuation in women of child-bearing potential and six months in males post last study drug.
- •Participants with Gilbert's disease.
- •Participants with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while participants with other prior malignancies must have had at least a 3-year disease-free interval.
- •Participants known to be human immunodeficiency (HIV) positive, hepatitis B positive, or hepatitis C positive.
- •Infection requiring antibiotic use within one week of randomization.
- •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.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Sacituzumab Govitecan
Participants will receive sacituzumab govitecan on Days 1 and 8 of a 21-day treatment cycle for up to 29.6 months. Participants will continue treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable adverse events (AEs).
干预措施: Sacituzumab govitecan (Drug)
Treatment of Physician's Choice (TPC)
Participants will receive TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent regimen that is selected by the investigator before participant randomization. Participants will continue treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable AEs.
干预措施: Eribulin (Drug)
Treatment of Physician's Choice (TPC)
Participants will receive TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent regimen that is selected by the investigator before participant randomization. Participants will continue treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable AEs.
干预措施: Capecitabine (Drug)
Treatment of Physician's Choice (TPC)
Participants will receive TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent regimen that is selected by the investigator before participant randomization. Participants will continue treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable AEs.
干预措施: Gemcitabine (Drug)
Treatment of Physician's Choice (TPC)
Participants will receive TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent regimen that is selected by the investigator before participant randomization. Participants will continue treatment until progression of disease requiring treatment discontinuation or occurrence of unacceptable AEs.
干预措施: Vinorelbine (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) by Independent Review Committee (IRC) Assessment in Brain Metastasis Negative (BM-ve) Population
时间窗: From randomization until objective tumor progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months)
PFS was defined as the time from randomization until objective tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death, whichever came first. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (greater than or equal to \[≥\] 20%) in the sum of the target lesions or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate.
次要结局
- Objective Response Rate (ORR) by IRC and Investigator Assessment in BM-ve Population(From randomization to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months))
- Duration of Response (DOR) by IRC and Investigator Assessment in BM-ve Population(From the first date of documented response of CR or PR to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months))
- Overall Survival (OS) in BM-ve Population(From the randomization to death from any cause (maximum follow-up duration: 30.8 months))
- Time to Objective Response by the IRC Assessment in BM-ve Population(From randomization to the first recorded objective response (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months))
- Progression-Free Survival (PFS) by IRC Assessment in the ITT Population(From randomization until objective tumor progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months))
- Overall Survival (OS) in ITT Population(From the randomization to death from any cause (maximum follow-up duration: 30.8 months))
- Percentage of Participants Experiencing Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation of Study Drug(First dose date up to last follow-up (maximum up to 30.8 months))
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Score(Baseline; End of Treatment (EOT) (up to 29.6 months))
- Time to Progression (TTP) by Investigator Assessment in BM-ve Population(From randomization until disease progression (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months))
- Time to Objective Response by the Investigator Assessment in BM-ve Population(From randomization to the first recorded objective response (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months))
- Time to Progression (TTP) by IRC Assessment in BM-ve Population(From randomization until disease progression (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months))
- Percentage of Participants Experiencing the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline(First dose date up to last follow-up (maximum up to 30.8 months))
- Clinical Benefit Rate (CBR) by IRC and Investigator Assessment in BM-ve Population(From randomization to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months))