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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
17
intramuscular injection (2x 250mg), once every 2 weeks for the first month, and then monthly until completion of the study
CHU de Liege
Grivegnée, Liège, Belgium
UZ Antwerp
Edegem, Belgium
UZ Gent
Ghent, Belgium
AZ Sint Maarten
Mechelen, Belgium
Gynaecological Oncology, Radboudumc
Nijmegen, Gelderland, Netherlands
medical Oncology, Maastricht University Medical Centrum+
Maastricht, Limburg, Netherlands
Gynecological Oncology Centrum, Catharina Ziekenhuis
Eindhoven, North Brabant, Netherlands
Amsterdam University Medical Centers (AMC)
Amsterdam, North Holland, Netherlands
The Netherlands Cancer Institute (NKI) - Antoni van Leuwenhoek Hospital (NKI-AvL)
Amsterdam, North Holland, Netherlands
Department of Obstetrics and Gynaecology, Leiden University Medical Center
Leiden, South Holland, Netherlands
...and 4 more locations
Response rate
partial or complete response, as determined by RECIST v1.1 criteria
Time frame: week 24
progression-free survival
progression-free survival after 3 years
Time frame: week 156
clinical benefit
Clinical benefit is defined as the number of patients having complete response, partial response or stable disease, as determined by RECIST v1.1 criteria
Time frame: week 24
duration of response
duration in weeks and days
Time frame: up to week 156
number of participants with treatment-related adverse events as assessed by CTCAE v5.0
absolute number of participants
Time frame: up to 56 days after stop study treatment
EQ-5D quality of life assessment
Quality of life as measured by the EQ-5D questionnaire. EQ-5D has 2 parts-the EQ-5D descriptive system and the EQ visual analog scale (EQ VAS). The descriptive system comprises 5 health states (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), which will be converted into a summary index according to the EQ-5D user guide. The EQ VAS records the self-rated health on an analog scale. For both EQ-5D index and EQ VAS, a higher score indicates a better health status. Descriptive statistics of the subscores and the summary score at each visit and the difference with baseline will be reported.
Time frame: 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 as measured by the EORTC-QLQ-C30 questionnaire. For EORTC QLQ-C30, functional scores (emotional, role, cognitive, physical, and social) will be pooled and a summary score will be calculated according to Giesinger et al. A higher score indicates better health for functioning and global health status, whereas for the symptom scales a lower score indicates a lower level of symptom burden. Descriptive statistics of the subscores and the summary score at each visit and the difference with baseline will be reported.
Time frame: Quality of life questionnaires will be completed by the patients at baseline and thereafter 3-monthly up to week 156
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