NCT03674242终止2 期
A Randomized Phase 2/3 Study of Eryaspase in Combination With Gemcitabine and Carboplatin Chemotherapy Versus Chemotherapy Alone for the Treatment of Patients With Metastatic or Locally Recurrent Triple-Negative Breast Cancer
ERYtech Pharma16 个研究点 分布在 3 个国家目标入组 27 人开始时间: 2019年6月13日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 27
- 试验地点
- 16
- 主要终点
- Disease Control Rate (DCR)
研究概览
简要总结
This is an open-label, multicenter, randomized, Phase 2/3 study in patients with locally recurrent or metastatic triple-negative breast cancer (TNBC) with no more than one prior systemic therapy for locally recurrent or metastatic disease.
详细描述
The study will consist of 2 parts:
- Part 1 is an open-label, multicenter, randomized Phase 2 exploratory study that will investigate the clinical activity of the combination of eryaspase and gemcitabine/carboplatin in patients with locally recurrent or metastatic TNBC. Data analysis of Part 1 will inform choices for the final design and patient population in Part 2 (Phase 3 study). Patients recruited into Part 1 will not be included in the Intent-to-Treat patient (ITT) population of Part 2 of the study.
- Part 2 will be a randomized Phase 3 study designed to evaluate the efficacy of the combination of eryaspase and gemcitabine/carboplatin in TNBC patients. The current protocol will focus on Part 1.
Part 1 is the focus of the current protocol, with a primary endpoint of DCR. DCR data as determined by an IRR will determine whether or not proceeding to Part 2 is warranted. If so, Part 2 will be implemented via a major amendment to the protocol. Meanwhile, sites will remain open with the expectation that Part 2 will be activated
After providing informed consent and completing the screening assessments, patients who meet all inclusion and no exclusion criteria will be randomized in a 1:1 ratio to one of the following treatment arms:
- Arm A (experimental arm): eryaspase 100 U/kg on Days 1 and 8 of combination chemotherapy with gemcitabine/carboplatin, or
- Arm B (control arm): gemcitabine/carboplatin combination.
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
- •Female or male, 18 years of age or older.
- •Histologically or cytologically confirmed diagnosis of invasive breast cancer.
- •Metastatic or locally recurrent inoperable breast cancer with no more than one prior systemic therapy.
- •Diagnosis (original primary tumor or subsequent relapse) of triple negative breast cancer, defined as the absence of expression of the following receptors in the primary and/or metastatic tumor tissue:
- •HER2 protein over-expression and/or gene amplification
- •Estrogen receptor (ER), defined as <1% staining by IHC (2).
- •AND progesterone receptors (PgR), defined as <1% staining by IHC.
- •Measurable lesion(s) per RECIST 1.
- •Available archival or fresh tumor tissue.
- •Adequate performance status (PS) score.
- •Life expectancy of >12 weeks according to the Investigator's clinical judgment.
- •Females of childbearing potential must have a negative pregnancy test at screening and an additional pregnancy test prior to first dose. Females of childbearing potential must agree to use a highly effective method of contraception during treatment and for at least 6 months after the last dose of study treatment.
- •Adequate laboratory parameters at baseline (obtained <14 days prior to randomization)
- •Patients must be able to understand and comply with the conditions of the protocol and must have read and understood the consent form and provided written informed consent.
排除标准
- •Pregnant or lactating females.
- •Known BRCA1 or BRCA2 mutation carrier.
- •Bone as the only site of disease.
- •Presence of untreated symptomatic central nervous system (CNS) metastases as determined by MRI or CT scan performed during screening.
- •Prior radiotherapy to the only area of measurable disease.
- •Prophylactic use of supportive bone-modifying therapy for skeletal-related events (e.g., bisphosphonate, pamidronate, or denosumab), unless treatment is initiated prior to or within 7 days after randomization.
- •History of recent clinical pancreatitis, according to revised Atlanta criteria, within 3 months of randomization.
- •Neurosensory neuropathy >Grade 2 at baseline.
- •Known history of infection with human immunodeficiency virus (HIV) and/or active infection with hepatitis B or hepatitis C.
- •Known hypersensitivity to gemcitabine, platinum compounds or asparaginase.
- •Patients who have received live or live attenuated vaccines within 3 weeks of randomization.
- •Pre-existing coagulopathy (e.g. hemophilia).
- •History of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for >2 years.
- •Any other severe acute or chronic condition/treatments that may increase the risk of study participation
- •Receiving therapy in a concurrent clinical study. Patients must agree not to participate in any other interventional clinical studies during their participation in this trial while on study treatment. Patients taking part in surveys or observational studies are eligible to participate in this study.
研究组 & 干预措施
Eryaspase plus Chemotherapy
Experimental
eryaspase 100 U/kg dosed at Day 1 and Day 8 of each 3-week cycle in combination with
- Gemcitabine IV infusion 1000 mg/m2, Day 1 and Day 8.
- Carboplatin IV infusion at a calculated area under the curve (AUC) of 2.0 (AUC2), Day 1 and Day 8.
干预措施: eryaspase (L-asparaginase encapsulated in red blood cells) (Drug)
Eryaspase plus Chemotherapy
Experimental
eryaspase 100 U/kg dosed at Day 1 and Day 8 of each 3-week cycle in combination with
- Gemcitabine IV infusion 1000 mg/m2, Day 1 and Day 8.
- Carboplatin IV infusion at a calculated area under the curve (AUC) of 2.0 (AUC2), Day 1 and Day 8.
干预措施: Gemcitabine (Drug)
Eryaspase plus Chemotherapy
Experimental
eryaspase 100 U/kg dosed at Day 1 and Day 8 of each 3-week cycle in combination with
- Gemcitabine IV infusion 1000 mg/m2, Day 1 and Day 8.
- Carboplatin IV infusion at a calculated area under the curve (AUC) of 2.0 (AUC2), Day 1 and Day 8.
干预措施: Carboplatin (Drug)
Chemotherapy alone
Active Comparator
Gemcitabine plus carboplatin dosed at Day 1 and Day 8 of each 3-week cycle
干预措施: Gemcitabine (Drug)
Chemotherapy alone
Active Comparator
Gemcitabine plus carboplatin dosed at Day 1 and Day 8 of each 3-week cycle
干预措施: Carboplatin (Drug)
结局指标
主要结局
Disease Control Rate (DCR)
时间窗: 1 year after last patient randomized
To determine whether the addition of eryaspase to gemcitabine and carboplatin improves the disease control rate (DCR) by modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by an independent radiological review (IRR) in patients with locally recurrent or metastatic triple-negative breast cancer (TNBC) compared with chemotherapy alone.
次要结局
- Progression-Free Survival (PFS)(1 year after last patient randomized.)
- Overall Survival (OS)(1 year after last patient randomized.)
- Disease Control Rate (DCR)(1 year after last patient randomized)
- Clinical response assessed by F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging(Collected at baseline and within 3 days of the end of Cycle 1 in all patients.)
- Pharmacokinetics of eryaspase(Samples will be collected the first day (D1) and the eight day (D8) of Cycle 1 and Cycle 3 treatment (each Cycle is 21 days) and at End of treatment (EOT))
- Objective response rate (ORR)(1 year after last patient randomized.)
- Duration of Response (DoR)(1 year after last patient randomized.)
- Incidence of treatment emergent adverse events as assessed by CTCAE v5.0(Collected from time of informed consent until 30 days after last study treatment.)
- Eryaspase induced immunogenecity(Samples will be collected pre-dose at Cycle 1 Day 1 and pre-dose at Cycle 3 Day 1 (each Cycle is 21 days))
- Biomarkers potentials in predicting eryaspase activity.(Tissue samples will be collected at baseline. Blood samples for biomarker analysis will be collected during screening, at Cycle 1 Day 1 and Day 8, and at Day 1 of every second cycle ( each is 21 days) until End of Treatment (EOT) visit.)
- Pharmacodynamics of eryaspase(Samples will be collected the first day (D1) and the eight day (D8) of Cycle 1 and Cycle 3 treatment (each Cycle is 21 days) and at End of treatment (EOT))
研究者
研究点 (16)
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