Multicenter, Open-label, Single Arm, Phase II Clinical Trial to Improve Sacituzumab Govitecan's Tolerance in Patients With Metastatic Triple-Negative or Luminal Breast Cancer.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 10
- 主要终点
- Incidence of grade ≥2 diarrhea
研究概览
简要总结
This is a multicenter, open-label, single-arm, multicohort, two-stage optimal Simon's design, phase II clinical trial that is designed to improve the tolerance of sacituzumab govitecan in patients with unresectable locally advanced or metastatic triple negative breast cancer (TNBC) or Luminal breast cancer, refractory to at least one, and no more than two, prior standard of care chemotherapy regimens in this setting that is not amenable to resection with curative intent.
The goal of this study is to evaluate the safety of sacituzumab govitecan in combination with loperamide and G-CSF in pretreated patients with unresectable locally advanced or metastatic TNBC or Luminal breast cancer.
详细描述
The hypothesis of this study is that the prophylactic administration of loperamide (for diarrhea) and G-CSF therapies (for neutropenia) would avoid these undesirable effects when patients are treated with sacituzumab govitecan, thus decreasing the rate of dose reduction or discontinuation, and significantly improving patients' quality of life.
The main objectives of this study are:
Primary objective:
- To evaluate the incidence of diarrhea and neutropenia in patients with unresectable locally advanced or metastatic TNBC or Luminal breast cancer treated with sacituzumab govitecan in combination with loperamide and G-CSF.
Secondary objectives:
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
盲法说明
Open label, single-arm
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
- •Signed Informed Consent Form (ICF) prior to participation in any study-related activities.
- •Patients aged ≥18 years at the time of signing ICF.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy of ≥ 12 weeks.
- •Unresectable locally advanced or metastatic disease documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
- •All patients must have been previously treated with taxanes regardless of disease stage (adjuvant, neoadjuvant, or advanced), unless contraindicated for a given patient.
- •Refractory to at least one, and no more than two, prior standard of care chemotherapy regimens for unresectable locally advanced or MBC. Earlier adjuvant or neoadjuvant therapy for more limited disease will be considered as one of the required prior regimens if the development of unresectable locally advanced or metastatic disease occurred within a 12-month period after completion of chemotherapy or immunotherapy (e.g., adjuvant pembrolizumab).
- •For TNBC patient only:
- •a.) Histologically confirmed TNBC per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria based on local testing on the most recent analyzed biopsy. Triple-negative is defined as <1% expression for estrogen receptor (ER) and progesterone receptor (PgR) and negative for human epidermal growth factor receptor 2 (HER2) (0-1+ by IHC or 2+ and negative by in situ hybridization [ISH) test].
- •For HR positive luminal breast cancer patients only:
- •Confirmed diagnosis of estrogen receptor (ER)[+] and/or progesterone receptor (PR)[+] (with ≥1% positive stained cells according to National Comprehensive Cancer Network [NCCN] and American Society of Clinical Oncology [ASCO] guidelines) and human epidermal growth factor receptor 2 (HER2)- negative (0 or 1+ by immunohistochemistry [IHC] or 2+ and negative by in situ hybridization [ISH] test) breast cancer in the advanced setting.
- •Refractory to at least 1 prior anticancer hormonal treatment and at least 1 CDKi4/6 in the metastatic setting.
- •Measurable or non-measurable, but evaluable disease, as per RECIST v.1.
- •Patients with bone-only metastases are also eligible.
- •Brain MRI must be done for patients with suspicion of brain metastases and patient must have stable central nervous system (CNS) disease for at least 4 weeks after local therapy, without neurological symptoms, and off anticonvulsants and steroids for at least 2 weeks before first dose of study treatment.
- •Adequate hematologic counts without transfusional or growth factor support within 2 weeks before of study drug initiation (hemoglobin ≥ 9 g/dL, ANC ≥ 1500/mm3, and platelets ≥ 100,000/μL).
- •Adequate renal and hepatic function (creatinine clearance of ≥ 60 ml/min, may be calculated using Cockcroft-Gault equation; bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 3.0 x ULN or 5 x ULN if known liver metastases).
- •Resolution of all acute AEs of prior anti-cancer therapy to grade 1 as determined by the NCI-CTCAE v.5.0 (except for alopecia or other toxicities not considered a safety risk for the patient at investigator discretion).
- •Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use institution specified method(s) of contraception.
- •Patients must have completed all prior cancer treatments at least 2 weeks* prior to randomization including chemotherapy (includes also endocrine treatment), radiotherapy, and major surgery.
- •Prior antibody treatment for cancer must have been completed at least 3 weeks prior to randomization.
排除标准
- •Prior treatment with topoisomerase 1 inhibitors as a free form or as other formulations.
- •Patients with carcinomatous meningitis or leptomeningeal disease.
- •Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances.
- •Patients with Gilbert's disease.
- •Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive.
- •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.
- •Known history of unstable angina, myocardial infarction, or cardiac heart failure present within 6 months of study initiation or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy or history of QT interval prolongation.
- •Known history of clinically significant active Chronic obstructive pulmonary disease (COPD), or other moderate-to-severe chronic respiratory illness present within 6 months of study initiation.
- •Known history of clinically significant bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of study initiation.
- •Active or prior documented inflammatory bowel disease (i.e. Crohn's disease, ulcerative colitis, or a preexisting chronic condition resulting in baseline grade ≥1 diarrhea).
- •Infection requiring antibiotic use within 1 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.
- •Women who are pregnant or lactating.
- •Concomitant participation in other interventional clinical trial. Note: Patients participating in observational studies are eligible.
研究组 & 干预措施
Sacituzumab Govitecan + Loperamide + G-CSF
Upon meeting all selection criteria, patients enrolled in the study will receive the combination of:
Sacituzumab govitecan :10 mg/kg, intravenously (IV) on Days 1 and 8 every 21-day cycle .
This treatment will continue until disease progression, unacceptable toxicity, or physician's/patient's decision.
Loperamide : 2 mg orally (PO), twice a day (BID), or 4 mg once a day (QD) during three consecutive days after administration of sacituzumab govitecan, (D2, D3, D4 and D9, D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician).
G-CSF : 30 MU subcutaneously (SC) QD during two consecutive days, 48 hours after administration of sacituzumab govitecan (D3, D4 and D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician).
干预措施: Sacituzumab govitecan (Drug)
Sacituzumab Govitecan + Loperamide + G-CSF
Upon meeting all selection criteria, patients enrolled in the study will receive the combination of:
Sacituzumab govitecan :10 mg/kg, intravenously (IV) on Days 1 and 8 every 21-day cycle .
This treatment will continue until disease progression, unacceptable toxicity, or physician's/patient's decision.
Loperamide : 2 mg orally (PO), twice a day (BID), or 4 mg once a day (QD) during three consecutive days after administration of sacituzumab govitecan, (D2, D3, D4 and D9, D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician).
G-CSF : 30 MU subcutaneously (SC) QD during two consecutive days, 48 hours after administration of sacituzumab govitecan (D3, D4 and D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician).
干预措施: Loperamide (Drug)
Sacituzumab Govitecan + Loperamide + G-CSF
Upon meeting all selection criteria, patients enrolled in the study will receive the combination of:
Sacituzumab govitecan :10 mg/kg, intravenously (IV) on Days 1 and 8 every 21-day cycle .
This treatment will continue until disease progression, unacceptable toxicity, or physician's/patient's decision.
Loperamide : 2 mg orally (PO), twice a day (BID), or 4 mg once a day (QD) during three consecutive days after administration of sacituzumab govitecan, (D2, D3, D4 and D9, D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician).
G-CSF : 30 MU subcutaneously (SC) QD during two consecutive days, 48 hours after administration of sacituzumab govitecan (D3, D4 and D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician).
干预措施: Granulocyte Colony-Stimulating Factor (Drug)
结局指标
主要结局
Incidence of grade ≥2 diarrhea
时间窗: Baseline up to end of 2nd cycle (day 42)
The rate of patients with grade ≥ 2 diarrhea is defined as the number of patients with diarrhea grade 2 to 5 the first 2 cycles of treatment by the number of patients in the analysis set per 100. The adverse events will be assessed by the Investigator and with severity determined using defined and graded according CTCAE v.5.0. The adverse events without the severity grade reported will be considered as grade 3.
Incidence of grade ≥3 neutropenia
时间窗: Baseline up to end of 2nd cycle (day 42)
The rate of patients with grade ≥ 3 neutropenia is defined as the number of patients with neutropenia grade 3 to 5 the first 2 cycles of treatment by the number of patients in the analysis set per 100. The adverse events will be assessed by the Investigator and with severity determined using defined and graded according CTCAE v.5.0. The adverse events without the severity grade reported will be considered as grade 3.
次要结局
- Incidence of all grades and grade ≥3 diarrhea.(Until EoS (26 months after study initiation))
- Incidence of all grades and grade ≥3 neutropenia.(Until EoS (26 months after study initiation))
- Incidence of febrile neutropenia and additional adverse events (AEs) as per NCI-CTCAE v.5.0.(Until EoS (26 months after study initiation))
- Discontinuation rate(Until EoS (26 months after study initiation))
- Dose reduction rate(Until EoS (26 months after study initiation))
- Objective response rate (ORR)(Until EoS (26 months after study initiation))
- Clinical benefit rate (CBR)(Until EoS (26 months after study initiation))
- Duration of response (DoR)(Until EoS (26 months after study initiation))
- Time to response (TtR)(Until EoS (26 months after study initiation))
- Best percentage of change from baseline in the size of target tumor lesions.(Until EoS (26 months after study initiation))
- Progression free survival (PFS)(Until EoS (26 months after study initiation))