A Phase 3, Randomized, Double-Blind Study of Trilaciclib or Placebo in Patients Receiving First- or Second-Line Gemcitabine and Carboplatin Chemotherapy for Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer (PRESERVE 2)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 194
- 试验地点
- 71
- 主要终点
- Effect on Overall Survival (OS)
研究概览
简要总结
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of trilaciclib versus placebo administered prior to gemcitabine and carboplatin in patients receiving first- or second-line treatment for locally advanced unresectable/metastatic TNBC.
详细描述
This study will have two separate cohorts (Cohort 1 and Cohort 2). Both cohorts will follow the same general study conduct/design with similar primary and key secondary endpoints and identical treatment arms.
- Cohort 1 will evaluate patients receiving first-line therapy, regardless of programmed death-ligand 1 (PD-L1) status, who are programmed cell death protein 1 (PD-1)/PD-L1 inhibitor therapy naïve.
- Cohort 2 will evaluate PD-L1 positive patients receiving second-line therapy following prior PD-1/PD-L1 inhibitor therapy in the locally advanced unresectable/metastatic setting.
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
- Double (Participant, Investigator)
盲法说明
Double-Blind Trial
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
- •Age >/= 18 years of age with evaluable locally advanced unresectable or metastatic TNBC.
- •Documentation of triple negative breast cancer (estrogen and progesterone receptor <1% and HER2-negative)
- •Prior systemic therapies (Cohort 1 only):
- •No prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, targeted therapy, immunotherapy, or investigational agents.
- •Prior PD-1/PD-L1 inhibitor treatment is not permitted in any setting, including in the neoadjuvant setting.
- •Time between completion of last treatment with curative intent and first metastatic recurrence must be ≥ 6 months.
- •Prior systemic therapies (Cohort 2 only):
- •Documentation of PD-L1 positive status
- •Treated with a PD-1/PD-L1 inhibitor for a minimum duration of 4 months in the locally advanced unresectable/metastatic setting and as the most recent therapy.
- •Radiation therapy for metastatic disease is permitted. There is no required minimum washout period for radiation therapy. Patients should be recovered from the effects of radiation.
- •Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate organ function as demonstrated by normal laboratory values
排除标准
- •Prior treatment with gemcitabine in any setting.
- •Prior treatment with carboplatin in the locally advanced unresectable/metastatic setting.
- •Prior carboplatin in the (neo)adjuvant/curative setting is permitted as long as it was completed ≥ 6 months prior to the first metastatic recurrence.
- •Presence of central nervous system (CNS) metastases and/or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
- •Receipt of any cytotoxic chemotherapy within 14 days prior to the first dose of study drugs.
- •QTcF interval >480 msec at Screening (confirmed in triplicate). For patients with ventricular pacemakers, QTcF >500 msec.
- •Known hypersensitivity to carboplatin or other platinum-containing compounds, or mannitol
- •Pregnant or lactating women
- •Prior hematopoietic stem cell or bone marrow transplantation
研究组 & 干预措施
Trilaciclib + gemcitabine + carboplatin
Trilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2)
干预措施: Trilaciclib (Drug)
Trilaciclib + gemcitabine + carboplatin
Trilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2)
干预措施: Gemcitabine (Drug)
Trilaciclib + gemcitabine + carboplatin
Trilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2)
干预措施: Carboplatin (Drug)
Placebo + gemcitabine + carboplatin
The subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib.
干预措施: Placebo (Drug)
Placebo + gemcitabine + carboplatin
The subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib.
干预措施: Gemcitabine (Drug)
Placebo + gemcitabine + carboplatin
The subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Effect on Overall Survival (OS)
时间窗: Cohort 2: From date of randomization up to 28 months
(Cohort 2): To evaluate the effect of trilaciclib on OS compared with placebo in patients receiving gemcitabine and carboplatin as second-line therapy after treatment with a PD-1/PD-L1 inhibitor in the locally advanced unresectable/metastatic setting
次要结局
- Myeloprotective Effects(Cycle 1 Day 1 (each cycle is 21 days) up to 14 months)
- Progression Free Survival(From date of randomization up to 14 months))
- Quality of life/Effects On Chemotherapy-Induced Fatigue(Cycle 1 Day 1 (each cycle is 21 days) up to 14 months)