A Phase I Study of LX-039 Tablets in Postmenopausal Patients With ER+, HER2- Advanced Breast Cancer After Failure of Endocrine Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- To explore the tolerance of LX-039 in ER +, HER2 - patients with advanced breast cancer
研究概览
简要总结
This is a phase I dose escalation and expansion study in patients with ER+, HER2- advanced breast cancer to explore the tolerance, PK/PD(pharmacokinetics/pharmacodynamics) profiles and preliminary anti-tumor activity of different doses of LX-039 tablets. The trial consists of two parts, dose escalation and dose expansion. Part 1 is the dose escalation phase with initial 6 dose groups, and "3 + 3" design is used to explore MTD of the drug; Part 2 is the dose expansion phase with 2 ~ 3 doses selected for expansion according to the escalation results of Part 1, and more subjects are enrolled to further observe the tolerance and preliminary anti-tumor activity of the drug. After the completion of dose expansion, the recommended phase II dose (RP2D) will be determined after discussion based on the obtained tolerance and PK/PD data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Be able to read and sign the informed consent form.
- •Adult females (aged ≥18 and ≤75 years).
- •Be diagnosed with breast cancer confirmed by pathological examination.
- •Be histologically or cytologically confirmed estrogen receptor positive (ER+≥1% positive staining).
- •Be postmenopausal.
- •Subjects who have previously received endocrine therapy and obtained benefit.
- •ECOG(Eastern Cooperative Oncology Group) score ≤
- •Subjects in part2 of the study need to have measurable lesions that meet RECIST 1.1 criteria.
- •Has recovered from toxicity or injury from prior chemotherapy/radiotherapy .
- •Enough hematology and organ function.
- •Expected survival>3 months.
排除标准
- •Subjects with HER2-overexpressing breast cancer.
- •Subjects with known brain metastases or other central nervous system metastases that are symptomatic or untreated.
- •Patients with symptomatic advanced disease who have spread to the viscera and are at risk of life-threatening complications.
- •Subjects who received second-line or above chemotherapy.
- •Subjects with known allergy to this product or any of its components.
- •Subjects who previously used other estrogen receptor down regulators than fulvestrant.
- •Subjects who received endocrine therapy or other anti-tumor agent or radiotherapy within 4 weeks prior to study entry.
- •Subjects who received cell therapy or tumor vaccine therapy;
- •Subjects with severe immunosuppression .
- •Severe or uncontrolled disease.
- •Subjects with diseases or abnormalities that may affect the administration and absorption of drugs.
- •Subjects with other malignancy within 5 years prior to study entry.
- •Subjects with other high risks of thrombosis or require long-term use of antiplatelet drugs.
- •Subjects with history of definite neurological or psychiatric disorders in the past.
- •Subjects who are HIV(human immunodeficiency virus) antibody positive, HBsAg(hepatitis B surface antigen) positive or HCV(hepatitis C virus)antibody positive.
- •Subjects with other uncontrolled malignant/non-malignant diseases, significant laboratory abnormalities, participation in the study may increase the risk.
研究组 & 干预措施
Part1：dose escalation
The investigational product for this study is LX-039 tablets,which can be administered orally. 6~8 ascending dose level until MTD and the specification included 50 mg, 100 mg, 200 mg, 400 mg, 600 mg , 800 mg,1050 mg and 1400 mg. LX-039 tablets will be administered in a therapeutic cycle of 28 days once a day orally. The subjects will continue therapy with LX-039 if good safety and tolerability were assessed by investigators after one cycle treatment. The treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
干预措施: LX-039 tablets (Drug)
Part 2：dose expansion
2~3 selected tolerable dose will be selected according to the tolerance and FES PET results of dose escalation phase.The subjects will continue therapy with LX-039 if good safety and tolerability were assessed by investigators after one cycle treatment. The treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
干预措施: LX-039 tablets (Drug)
结局指标
主要结局
To explore the tolerance of LX-039 in ER +, HER2 - patients with advanced breast cancer
时间窗: DLT observation period(5 weeks for dose escalation, 4 weeks for dose expansion)
Incidence of dose limiting toxicities (DLTs)
次要结局
- The safety of LX-039 in ER +, HER2 - patients with advanced breast cancer(through study completion,an average of 1 year)
- To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.(through study completion，an average of 1 year.)
- Comparison of changes in maximum uptake ability of FES(progression free survival) in breast cancer lesions before and after treatment with LX-039 by PET(positron emission tomography) scan (performed in some subjects)(Up to the third day of Cycle 2(each cycle is 28 days))
- PK profiles after a single dose of LX-039(Up to the third day of Cycle 0(Cycle 0 is 7 days))
- PK profiles after continuous administration of LX-039(Up to the Second day of Cycle 2(each cycle is 28 days))