Overview

FUlvestrant in Gynecological Cancers That Are Potentially Hormone Sensitive: the FUCHSia Study

Status:
Recruiting
Trial end date:
2025-12-31
Target enrollment:
0
Participant gender:
Female
Summary
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Frederic Amant
Collaborators:
FWO Research Fund Flanders
Kom Op Tegen Kanker
Kom op tegen Kanker (Stand-up-to-Cancer), the Flemish cancer society
Treatments:
Fulvestrant
Criteria
Inclusion Criteria:

- 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 1. 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

Exclusion Criteria:

- 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