ToPCourT: A Phase II Trial of Trilaciclib, Pembrolizumab, Gemcitabine and Carboplatin in Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer (TNBC)
概览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Objective Response
概览
简要总结
The goal of this phase II study is to test the combination of trilaciclib, pembrolizumab, gemcitabine, and carboplatin in locally advanced unresectable or metastatic triple-negative breast cancer.
The main questions it aims to answer are:
- to evaluate the anti-cancer efficacy (assess how well it works)
- to evaluate the safety and tolerability (how well the body can handle the treatment) of this combination of anti-cancer therapy
详细描述
This is an open label, single-arm, phase II trial designed to evaluate the efficacy of trilaciclib, pembrolizumab, gemcitabine and carboplatin in participants with locally advanced unresectable or metastatic triple-negative breast cancer. Pembrolizumab will be given for a maximum of 2 years. Eligible participants will receive the study treatment until disease progression, unacceptable toxicity, or withdrawal for any reason. A tumor biopsy will be collected from participants in which it can be safely obtained before the first dose of treatment, prior to Cycle 3 Day 1, and at the time of disease progression (optional). Blood specimens for correlative studies will be collected pre-treatment Cycle 1 Day 1, prior to treatment Cycle 2 Day 1, prior to treatment Cycle 3 Day 1, 3 months after the start of study treatment, and 6 months after the start of study treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Written informed consent and HIPAA authorization for release of personal health information signed by the patient
- •Male or female with locally advanced unresectable or metastatic TNBC
- •Age ≥ 18 years at the time of consent
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 evaluated within 28 days prior to day 1 of study treatment
- •Histological or cytological confirmation of estrogen negative and progesterone negative tumor, defined as \< 10% staining on immunohistochemistry (IHC) and human epidermal growth factor receptor type 2 (HER2)-negative, defined as HER 2 IHC 0 or 1+ or IHC 2+ with no amplification. Patients may be enrolled regardless of their PD-L1 (programmed death ligand-1) status.
- •Measurable disease according to response evaluation criteria in solid tumors
- •Demonstrate adequate organ function
- •Female patients: All females of childbearing potential must have a negative serum β-human chorionic gonadotropin (hCG) test result at Screening and negative serum or urine pregnancy test results within 72 hours prior to day 1 of study treatment.
- •Subject agrees to use contraception
- •As determined by the enrolling physician, the ability of the subject to understand and comply with study procedures for the entire length of the study
排除标准
- •More than 3 prior lines of chemotherapy for locally advanced unresectable or triple-negative metastatic disease
- •Prior therapy with the concurrent combination of gemcitabine and carboplatin in the metastatic setting
- •Active, symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis or CNS metastases that are progressing on screening magnetic resonance imaging (MRI) brain.
- •Prior systemic anti-cancer therapy within 3 weeks, prior stereotactic radiotherapy within 1 week, and radiation within 2 weeks of day 1 of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation to non-CNS disease.
- •Major surgery, defined by the investigator's discretion, within 3 weeks of day 1 of study treatment
- •Not recovered from all reversible acute toxic effects of prior therapy, including non-hematologic toxicities related to prior systemic therapy to ≤ Grade
- •Participants with less than Grade 2 neuropathy or alopecia of any grade are an exception
- •Active infection requiring systemic therapy
- •Pregnant or breastfeeding
- •Participants previously diagnosed with an additional malignancy must be disease-free for at least five years prior to enrollment. Exceptions include basal cell or squamous cell skin cancer and in situ cervical or bladder cancer.
研究组 & 干预措施
Trilaciclib, Pembrolizumab, Gemcitabine, and Carboplatin
Trilaciclib is an agent that helps protect the bone marrow from the side effects of chemotherapy. It is given as an intravenous (IV) infusion over 30 minutes prior to gemcitabine and carboplatin. Gemcitabine is given IV over 30 minutes. Carboplatin is given over 30 minutes. Trilaciclib, gemcitabine and carboplatin are given on Days 1 and 8 every 21 days. Pembrolizumab is given IV over 30 minutes on Day 1 every 21 days.
干预措施: Trilaciclib (Drug)
Trilaciclib, Pembrolizumab, Gemcitabine, and Carboplatin
Trilaciclib is an agent that helps protect the bone marrow from the side effects of chemotherapy. It is given as an intravenous (IV) infusion over 30 minutes prior to gemcitabine and carboplatin. Gemcitabine is given IV over 30 minutes. Carboplatin is given over 30 minutes. Trilaciclib, gemcitabine and carboplatin are given on Days 1 and 8 every 21 days. Pembrolizumab is given IV over 30 minutes on Day 1 every 21 days.
干预措施: Pembrolizumab (Drug)
Trilaciclib, Pembrolizumab, Gemcitabine, and Carboplatin
Trilaciclib is an agent that helps protect the bone marrow from the side effects of chemotherapy. It is given as an intravenous (IV) infusion over 30 minutes prior to gemcitabine and carboplatin. Gemcitabine is given IV over 30 minutes. Carboplatin is given over 30 minutes. Trilaciclib, gemcitabine and carboplatin are given on Days 1 and 8 every 21 days. Pembrolizumab is given IV over 30 minutes on Day 1 every 21 days.
干预措施: Gemcitabine (Drug)
Trilaciclib, Pembrolizumab, Gemcitabine, and Carboplatin
Trilaciclib is an agent that helps protect the bone marrow from the side effects of chemotherapy. It is given as an intravenous (IV) infusion over 30 minutes prior to gemcitabine and carboplatin. Gemcitabine is given IV over 30 minutes. Carboplatin is given over 30 minutes. Trilaciclib, gemcitabine and carboplatin are given on Days 1 and 8 every 21 days. Pembrolizumab is given IV over 30 minutes on Day 1 every 21 days.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Objective Response
时间窗: 6 months (initiation of protocol directed therapy until either a partial response is achieved or treatment discontinuation)
Objective according to RECIST v1.1 criteria
次要结局
- Progression-free survival(1 year (initiation of protocol directed therapy until documented disease progression, death, or end of follow-up period))
- Overall survival(1 year (initiation of protocol directed therapy until documented death, or end of follow-up period]))
- Duration of response(1 year (time from first disease assessment that shows a PR or complete response (CR) until documented disease progression, death, or end of follow-up period))