An Open-label, Single Arm, Prospective, Multi-center, Tandem Two Stage Designed, Phase II Study to Evaluate the Efficacy of Fulvestrant in Women With Recurrent/Metastatic Estrogen Receptor Positive Gynecological Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 试验地点
- 14
- 主要终点
- Response rate
研究概览
简要总结
This phase 2 clinical trial aims to evaluate the efficacy of Fulvestrant, an ER-antagonist, in women with estrogen receptor positive (ER+) low-grade gynecological cancers. The primary objective is to determine the response rate (RR) to Fulvestrant, defined by partial or complete response according to RECIST v1.1 criteria. Secondary objectives include assessing progression-free survival (PFS) over 3 years, clinical benefit (CB), duration of response, safety and tolerability, and quality of life (QoL) in each tumor type group. Exploratory objectives involve evaluating the feasibility of 18F-FES PET imaging for detecting ER expression, the predictive value of sequential 18F-FES PET scans for treatment response, and collecting tumor biopsies and cf-DNA for genetic analysis to identify adaptive response mechanisms to Fulvestrant.
详细描述
In this phase 2 clinical trial, the aim is to evaluate the efficacy of the ER-antagonist Fulvestrant in women with estrogen receptor positive (ER+) low grade gynecological cancers. The primary objective of the study is to determine the response rate (RR) upon Fulvestrant treatment, comprising either partial or complete response, as determined by RECIST v1.1 criteria for each tumor type. The secondary objectives are to: (1) determine progression-free survival (PFS) upon Fulvestrant treatment, after 3 years, in each tumor type group (2) assess clinical benefit (CB) upon Fulvestrant treatment, comprising complete response, partial response and stable disease, as determined by RECIST v1.1 criteria, in each tumor type group (3) assess duration of response in each tumor type group (4) assess safety and tolerability of Fulvestrant administration in each tumor type group (5) assess quality of life (QoL) and symptoms in each tumor type group. As exploratory objectives, the aim is to: (1) evaluate the feasibility of 16α-18F-fluoro-17β-estradiol (18F-FES) PET imaging for detection of ER expression (2) determine the value of sequential 18F-FES PET scans in predicting response to Fulvestrant (3) collect tumor biopsies and cf-DNA from patients enrolled in the trial. These samples will be subsequently characterized at the genetic level, to identify adaptive response mechanisms to Fulvestrant treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- Female
- 接受健康志愿者
- 否
入选标准
- •Written informed consent prior admission to the study
- •Age ≥ 18 years at the moment of signing the informed consent
- •Recurrent or metastatic low grade uterine sarcomas (low grade endometrial stromal sarcoma, low grade adenosarcoma without sarcomatous overgrowth and low grade leiomyosarcoma), low-grade endometrial carcinomas, sex cord stromal tumors (granulosa cell tumors...) and low grade serous ovarian cancer
- •Measurable disease, according to RECIST v1.1 criteria, assessed by CT scans
- •ER-positive tumors based on immunohistochemistry, assessed using the Allred scoring system (based on intensity and percentage of positive cells, see Appendix 4), and archival tissue available
- •At least and maximum of 1 prior line of hormonal therapy (tamoxifen, progestins and/or aromatase inhibitors). Response on 1st line hormonal therapy must have lasted for at least 3 months.
- •Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
- •Demonstrate adequate organ function: platelets > 100 x 10E9/L, serum total bilirubin < 1.5x Upper Limit of Normal (ULN) (patients with confirmed Gilbert's syndrome may be included in the study), alanine transaminase or aspartate transaminase < 2.5x ULN if no demonstrable liver metastases or < 5x ULN in presence of liver metastases
- •Post-menopausal status as defined by (i) age 60 or more, or (ii) age 45-59 and satisfying the following criteria: amenorrhea for at least 12 months and FSH in postmenopausal range, or (iii) ≥ 18 years of age and having had a bilateral oophorectomy
- •Be willing to receive 18F-FES PET scan. Exceptions will be made in case of (i) patients living far from one of the imaging centers and for whom travelling would be a too high burden for their physical conditions; (ii) patients who received tamoxifen within 8 weeks prior to study Day
- •These patients will be enrolled, but they will not receive a FES PET scan
- •Be willing to donate a core tumor biopsy if technically feasible
排除标准
- •Any other active malignancy or primary malignancy diagnosed within the previous 5 years, except for adequately treated squamous or basal cell carcinoma of the skin or in situ cervical carcinoma
- •Patients currently receiving (and unwilling to discontinue) any estrogen replacement therapy.
- •Patients participating in a study or having participated in a study of an investigational agent and received study therapy (or used an investigational device) within 4 weeks prior to study Day 1
- •Patients who received prior chemo- or targeted therapy within 4 weeks prior to study Day 1 or who has not recovered from adverse events (i.e., adverse event not resolved to ≤ Grade 1 or baseline), due to a previously administered agent
- •Patients with no archival tissue available, except for patients from whom an additional fresh core biopsy can be obtained for ER assessment
- •Any other disease, metabolic dysfunction, physical examination or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interfere with obtaining informed consent.
- •Any condition not permitting compliance with the study protocol
研究组 & 干预措施
Low-grade uterine sarcoma
Participants with low-grade uterine sarcoma
干预措施: Fulvestrant (Drug)
low-grade endometrial carcinoma
Participants with low-grade endometrial carcinoma
干预措施: Fulvestrant (Drug)
sex cord stromal tumors
Participants with sex cord stromal tumors
干预措施: Fulvestrant (Drug)
low-grade serous ovarian cancer
Participants with low-grade serous ovarian cancer
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Response rate
时间窗: week 24
partial or complete response, as determined by RECIST v1.1 criteria
次要结局
- duration of response(up to week 156)
- progression-free survival(week 156)
- clinical benefit(week 24)
- number of participants with treatment-related adverse events as assessed by CTCAE v5.0(up to 56 days after stop study treatment)
- EQ-5D quality of life assessment(Quality of life questionnaires will be completed by the patients at baseline and thereafter 3-monthly up to week 156)
- EORTC QLQ-C30 quality of life assessment(Quality of life questionnaires will be completed by the patients at baseline and thereafter 3-monthly up to week 156)
研究者
Frederic Amant
Professor
University Hospital, Gasthuisberg