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

NCT ID: NCT03926936

Last Updated: 2024-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-13
• Study Completion Date: 2022-12-27

Brief Summary

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.

Detailed Description

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.

Conditions

Endometrial Stromal Sarcoma; Adenosarcoma of Uterus; Leiomyosarcoma Uterus; Endometrial Cancer; Sex Cord Stromal Tumor; Serous Ovarian Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low-grade uterine sarcoma

Participants with low-grade uterine sarcoma

Group Type: EXPERIMENTAL

Fulvestrant

Intervention Type: DRUG

intramuscular injection (2x 250mg), once every 2 weeks for the first month, and then monthly until completion of the study

low-grade endometrial carcinoma

Participants with low-grade endometrial carcinoma

Group Type: EXPERIMENTAL

Fulvestrant

Intervention Type: DRUG

intramuscular injection (2x 250mg), once every 2 weeks for the first month, and then monthly until completion of the study

sex cord stromal tumors

Participants with sex cord stromal tumors

Group Type: EXPERIMENTAL

Fulvestrant

Intervention Type: DRUG

intramuscular injection (2x 250mg), once every 2 weeks for the first month, and then monthly until completion of the study

low-grade serous ovarian cancer

Participants with low-grade serous ovarian cancer

Group Type: EXPERIMENTAL

Fulvestrant

Intervention Type: DRUG

intramuscular injection (2x 250mg), once every 2 weeks for the first month, and then monthly until completion of the study

Interventions

Fulvestrant

intramuscular injection (2x 250mg), once every 2 weeks for the first month, and then monthly until completion of the study

Intervention Type: DRUG

Other Intervention Names

Faslodex

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Kom Op Tegen Kanker

OTHER

Sponsor Role: collaborator

Research Foundation Flanders

OTHER

Sponsor Role: collaborator

Frederic Amant

OTHER

Sponsor Role: lead

Responsible Party

Frederic Amant

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Frédéric Amant, MD PhD

Role: PRINCIPAL_INVESTIGATOR

UZ Leuven

Locations

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

Gynaecological Oncology, Erasmus MC Cancer Institute

Rotterdam, South Holland, Netherlands

Center for Medical Imaging, University Medical Centrum Groningen

Groningen, , Netherlands

Obstetrics and Gynaecology, University Medical Centrum Groningen

Groningen, , Netherlands

University Medical Centrum Utrecht

Utrecht, , Netherlands

Countries

Belgium; Netherlands

Other Identifiers

2017-005018-76

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

S60857

Identifier Type: -

Identifier Source: org_study_id