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

NCT03926936 | Completed Phase 2 DMC

• 2 other identifiers: S608572017-005018-76
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 14

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.

Conditions

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

Keywords

fulvestrant; low-grade gynecological cancer; efficacy

Outcome Measures

Primary Outcomes (1)

• Response rate

  partial or complete response, as determined by RECIST v1.1 criteria

  week 24

Secondary Outcomes (6)

• progression-free survival

  week 156

• clinical benefit

  week 24

• duration of response

  up to week 156

• 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

Other Outcomes (3)

• Detection of ER expression by 18F-FES PET imaging

  up to week 156

• Predicting response to Fulvestrant by sequential 18F-FES PET imaging

  up to week 156

• Genomic analysis of blood and tumor biopsies

  up to week 156

Study Arms (4)

Low-grade uterine sarcoma

EXPERIMENTAL

Participants with low-grade uterine sarcoma

Drug: Fulvestrant

low-grade endometrial carcinoma

EXPERIMENTAL

Participants with low-grade endometrial carcinoma

Drug: Fulvestrant

sex cord stromal tumors

EXPERIMENTAL

Participants with sex cord stromal tumors

Drug: Fulvestrant

low-grade serous ovarian cancer

EXPERIMENTAL

Participants with low-grade serous ovarian cancer

Drug: Fulvestrant

Interventions

Fulvestrant DRUG

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

Also known as: Faslodex

Low-grade uterine sarcoma; low-grade endometrial carcinoma; low-grade serous ovarian cancer; sex cord stromal tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Frederic Amant: lead
• Kom Op Tegen Kanker: collaborator
• Research Foundation Flanders: collaborator

Study Sites (14)

CHU de Liege

Grivegnée, Liège, 4030, Belgium

Location

UZ Antwerp

Edegem, 2650, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

AZ Sint Maarten

Mechelen, 2800, Belgium

Location

Gynaecological Oncology, Radboudumc

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

medical Oncology, Maastricht University Medical Centrum+

Maastricht, Limburg, 6202 AZ, Netherlands

Location

Gynecological Oncology Centrum, Catharina Ziekenhuis

Eindhoven, North Brabant, 5623 EJ, Netherlands

Location

Amsterdam University Medical Centers (AMC)

Amsterdam, North Holland, 1000, Netherlands

Location

The Netherlands Cancer Institute (NKI) - Antoni van Leuwenhoek Hospital (NKI-AvL)

Amsterdam, North Holland, 1000, Netherlands

Location

Department of Obstetrics and Gynaecology, Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

Location

Gynaecological Oncology, Erasmus MC Cancer Institute

Rotterdam, South Holland, 3075 EA, Netherlands

Location

Center for Medical Imaging, University Medical Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Obstetrics and Gynaecology, University Medical Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

University Medical Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

MeSH Terms

Conditions

Sarcoma, Endometrial Stromal; Adenosarcoma of the uterus; Endometrial Neoplasms; Sex Cord-Gonadal Stromal Tumors

Interventions

Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Endometrial Stromal Tumors; Sarcoma; Neoplasms, Connective and Soft Tissue; Uterine Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Neoplasms by Site; Neoplasms, Gonadal Tissue

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Frédéric Amant, MD PhD

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: April 25, 2019
• Study Start: March 13, 2019
• Primary Completion: April 1, 2022
• Study Completion: December 27, 2022
• Last Updated: May 28, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The data will be available from the moment it is entered into the study. From then on, all data will be kept for 20 years.
• Access Criteria: The sponsor will be the data controller and data can only be requested when a protocol has been approved.

Locations

NL (10); BE (4)