NCT07840443尚未招募2 期
Phase II Window-of-Opportunity Study Evaluating the Pharmacodynamic Effects of Camizestrant in Early-Stage Estrogen Receptor-Positive Endometrial Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 6
- 主要终点
- Absolute change in in ER expression by H-score
研究概览
简要总结
This is a window of opportunity study designed to provide short duration exposure to camizestrant prior to planned curative intent surgery, with the anticipated benefit of demonstrating target engagement and suppression of ER signalling in ER positive endometrial cancer without delaying standard surgical management.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Participants must provide informed consent prior to undergoing any study-specific procedures.
- •Only female participants aged 18 years or older are eligible for inclusion.
- •Participants must have a histologically confirmed, newly diagnosed, resectable endometrial adenocarcinoma with the following characteristics determined by local pathology:
- •ER positivity equal or greater than 10%
- •TP53 wildtype status by IHC.
- •Proficient mismatch repair (pMMR) by IHC
- •Any histology and grade is acceptable
- •FIGO stage I-III
- •Female participants must have a newly diagnosed primary endometrial cancer and be scheduled for radical surgery, regardless of their clinical node status.
- •Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
- •Participants must have adequate bone marrow reserve and organ function as demonstrated by the following laboratory values:
- •Hemoglobin (Hb): > 80 g/L
- •Platelet count: > 100 × 10⁹/L
- •Creatinine < 1.5 × ULN
- •AST and ALT: < 3 × Upper Limit of Normal (ULN)
- •Total Bilirubin: < 1.5 × ULN
- •Participants must be post-menopausal, which can be clinically defined as 12 consecutive months without a menstrual period as reported by the patient in the absence of endocrine therapies or patient with bilateral oophorectomy.
- •Participants must be willing to provide pre-treatment baseline tumor tissue (from diagnostic biopsy) and tissue from the surgical procedure for biomarker analyses and blood samples for ctDNA analysis.
排除标准
- •Participants must not have received any previous systemic or local treatment for the new primary endometrial cancer currently under investigation. This includes surgery, radiotherapy, cytotoxic treatments, and endocrine therapies.
- •Participants must not have had any of the following interventions:
- •Use of sex-hormone-containing drugs within one month prior to the first dose of study treatment and concurrent use of hormonal treatments (such as for menopausal symptoms).
- •Medicinal products that are sensitive substrates (e.g. omeprazole) or substrates with narrow therapeutic index of CYP2C9 and/or CYP2C19 (e.g. warfarin and phenytoin) should be stopped at least 2 weeks before the first dose of camizestrant.
- •Strong CYP3A4/5 inducers (e.g. carbamazepine ) should be should be stopped at least 2 weeks before the first dose of camizestrant (3 weeks for St John's Wort)
- •Use of drugs known to prolong the QT interval and carry a known risk of torsades de pointes within the timeframe indicated in Table 5 (Appendix D) prior first dose of camizestrant.
- •Ivabradine or other drugs with a similar mechanism of action in sinoatrial cells.
- •Participants must not have any evidence of severe or uncontrolled systemic diseases that, in the investigator's opinion, would make participation in the study undesirable.
- •Participants must not meet any of the following cardiovascular criteria:
- •Electrolyte Abnormalities: Untreated serum or plasma potassium, magnesium, or calcium levels outside the normal limit range that could prolong the QT interval. These are: clinically significant electrolyte abnormalities with potential QT-prolonging effect including hypokalaemia, hyperkalaemia, hypo- and hyper-magnesaemia, hypo- and hyper-calcaemia.
- •ECG Abnormalities:
- •Mean resting QTcF interval > 460 milliseconds at screening
- •Bradycardia (heart rate < 60 bpm)
- •Clinically significant abnormalities in rhythm, conduction, or morphology of the resting ECG, such as second- or third-degree heart block, clinically significant sinus pause or sinoatrial block, other sinus node dysfunction, or bundle branch block. Patients with pacemakers or medically controlled atrial fibrillation are not excluded. Note: A digital triplicate ECG is mandated during screening
- •Any other condition that increase the risk of QTc prolongation or the risk of arrhythmic events such as symptomatic heart failure, congenital long QT syndrome, immediate family history of long QT syndrome and unexplained sudden death at <40 years of age, hypertrophic cardiomyopathy and clinically significant stenotic valve disease.
- •c. Participants must not have experienced unexplained syncope within the six months prior to randomization, ongoing symptomatic hypotension, or ongoing asymptomatic hypotension with systolic blood pressure less than 90 mmHg.
- •d. Patients with pacemakers or medically controlled atrial fibrillation are not excluded.
- •e. Participants must not have a known left ventricular ejection fraction less than 50% and/or heart failure classified as NYHA Grade greater than or equal to
- •f. Participants must not have uncontrolled hypertension, defined as systolic blood pressure greater than 160 mmHg and diastolic blood pressure greater than 90 mmHg despite optimal medical management. Hypertensive patients may be eligible if blood pressure is adequately controlled at baseline.
- •g. Participants must not have experienced any cardiovascular procedure or event within the last 6 months such as: Coronary artery bypass graft, angioplasty, vascular stent placement, other structural heart disease interventions (e.g., cardiac valve repair or replacement surgery or transcatheter valve treatment), severe aortic regurgitation (Grades 3 and 4), myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack.
- •Participants must not have refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases, an inability to swallow the formulated product, or a history of significant bowel resection that would preclude adequate absorption of camizestrant.
- •Participants must not have a history of hypersensitivity to any active or inactive excipients of camizestran
- •Participants must not be enrolled if, in the investigator's judgment, they are unlikely to comply with study procedures, restrictions, and requirements.
- •Pregnant patients or breastfeeding
研究组 & 干预措施
Camizestrant
Experimental
Camizestrant 75mg QD for 4 weeks (+/- 2 weeks) prior to surgery
干预措施: Camizestrant (Drug)
结局指标
主要结局
Absolute change in in ER expression by H-score
时间窗: 2 years
Percentage change in ER expression by H-score
时间窗: 2 year
次要结局
- Absolute change in in PR expression by H-score(2 years)
- Percentage change in PR expression by H-score(2 years)
- Absolute change in Ki-67 by IHC scoring(2 years)
- Percentage change in Ki-67 by IHC scoring(2 years)
- Pathological response rate(2 years)
- Plasma concentration of camizestrant at the time of surgery(2 years)
- Number of participants with any AE/SAE from first dose through safety follow-up(2 years)
- Percentage of participants with any AE/SAE from first dose through safety follow-up(2 years)
研究者
研究点 (6)
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