A Phase 1 Dose Escalation and Expansion Study of AZD9833 Alone or in Combination With Palbociclib or Everolimus in Chinese Patients With Oestrogen Receptor Positive (ER+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer (mBC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- The number of subjects with dose-limiting toxicity, as defined in the protocol.
研究概览
简要总结
A Phase 1 Dose Escalation and Expansion Study of AZD9833 Alone or in Combination in Chinese patients with ER Positive, HER2 Negative, Metastatic Breast Cancer
详细描述
This study is designed to investigate and characterize the safety, tolerability and PK of AZD9833 monotherapy (Part A, Part B-cohort 1) or in combination with palbociclib (optional Part B cohort 2) or everolimus (optional Part B cohort 3) and to explore the preliminary anti-tumour activity in Chinese patients
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Any menopausal status:
- •Pre-menopausal women must have commenced treatment with an LHRH agonist at least 4 weeks prior to the start of study intervention and must be willing to continue to receive LHRH agonist therapy for the duration of the study.
- •Post-menopausal defined according to standard criteria in the protocol.
- •Histological or cytological confirmation of adenocarcinoma of the breast.
- •Documented positive ER status and HER2 negative status of primary or metastatic tumour tissue.
- •ECOG performance status 0 to
- •Metastatic disease and radiological or objective evidence of progression on or after the last systemic therapy prior to the start of study intervention.
- •At least one lesion as per RECIST Version 1.1 that can be accurately assessed at baseline and is suitable for repeated assessment by CT, MRI, or plain X-ray or clinical examination.
- •Recurrence or progression on at least one line of endocrine therapy in the metastatic disease setting.
- •For Part A and Part B cohort 1, patients should be eligible for SERD monotherapy treatment.
- •For Part B Cohort 2, patients should be eligible for SERD treatment and CDK4/6 inhibitors, and prior treatment with CDK4/6 inhibitors is not permitted.
- •For Part B Cohort 3, patients should be eligible for SERD treatment and mTOR inhibitors, and prior treatment with mTOR inhibitors is not permitted.
排除标准
- •Previous treatment with AZD
- •Presence of life-threatening metastatic visceral disease, uncontrolled CNS metastatic disease or life-threatening extensive hepatic involvement.
- •Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, or infection requiring intravenous antibiotic therapy, which makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol.
- •Inadequate bone marrow reserve or organ function.
- •Any clinically important and symptomatic heart disease.
- •Any concurrent anti-cancer treatment.
- •Refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9833 (and palbociclib and everolimus).
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
AZD9833 monotherapy dose escalation
干预措施: AZD9833 (Drug)
AZD9833 monotherapy dose expansion
干预措施: AZD9833 (Drug)
AZD9833 with palbociclib dose expansion
干预措施: AZD9833 with palbociclib (Drug)
AZD9833 with everolimus dose expansion
干预措施: AZD9833 with everolimus (Drug)
结局指标
主要结局
The number of subjects with dose-limiting toxicity, as defined in the protocol.
时间窗: Minimum observation period 28 days on treatment.
Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria of AZD9833 monotherapy. \[part A only\]
Plasma AZD9833 concentrations and derived PK parameters.
时间窗: At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )
To characterise the single- and multiple-dose PK of AZD9833 monotherapy.
The number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.
时间窗: 6 months after the last patient recruited starts study intervention or 28 days after the final patient discontinues study intervention
Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of subjects with treatment-related adverse events assessed by CTCAE v5.0 of AZD9833 monotherapy.
次要结局
- Clinical benefit rate at 24 weeks(Up to 24 weeks)
- Progression Free Survival(From start of treatment to disease progression/latest date of evaluable RECIST assessment (approximate 1 year))
- Plasma AZD9833 concentrations and derived PK parameters (for optional expansion cohorts Part B Cohorts 2 and 3 only). Everolimus (whole blood) concentrations and derived PK parameters (for optional expansion cohort Part B Cohort 3 only).(At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks ))
- Duration of Response(Week 8 and week 16 and week 24 and then every 12 weeks (weeks 36, 48 and 60) until the end of the study (approximately 1 year))
- The number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.(6 months after the last patient recruited starts study intervention or 28 days after the final patient discontinues study intervention)
- Objective Response Rate(Week 8 and week 16 and week 24 and then every 12 weeks (week 36, 48, 60) until the end of the study (approximately 1 year))
- Percentage Change in Tumour Size(Week 8 and week 16 and week 24 and then every 12 weeks (weeks 36, 48 and 60) until the end of the study (approximately 1 year))