Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Ovarian Neoplasms

Hypersensitivity

Sarcoma

Recurrence

Sarcoma, Endometrial Stromal

Leiomyosarcoma

Sex Cord-Gonadal Stromal Tumors

Adenosarcoma

Endometrial Neoplasms

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Endometrial Stromal Tumors

Ovarian Cancer

Soft Tissue Sarcoma

Endometrial Stromal Sarcoma

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Fulvestrant

Estrogens

Antineoplastic Agents, Hormonal

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Participants with low-grade uterine sarcoma

Participants with low-grade endometrial carcinoma

Participants with sex cord stromal tumors

Participants with low-grade serous ovarian cancer

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

Frédéric Amant, MD PhD

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.

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

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

* Demographics
* Medication and Medical history
* Physical examination
* Height
* Weight
* Vital signs
* ECOG status
* Core biopsy
* Blood tests (hematological and chemical panels)
* Blood sample for cf-DNA analysis
* CT and/or MR scan (chest-abdomen/pelvis)
* 18F-FDG PET/CT scan
* 18F-FES PET/CT or PET/MRI scan
* QoL assessment
* Fulvestrant administration
* Adverse Events

16α-18F-fluoro-17β-estradiol (18F-FES) positron emission tomography (PET) technique uses a radiolabeled estrogen derivative and allows non-invasive, repetitive imaging of the ER receptor, mainly the α subtype.

This technique has been validated for measurement of ER expression in breast cancer.

PET parameters will be derived from the PET data at baseline and will be correlated to the treatment response and the survival of the patients (PFS and OS). Liver metastases will not be included in the analysis due to high physiologic background uptake.

16α-18F-fluoro-17β-estradiol (18F-FES) positron emission tomography (PET) uses a radiolabeled estrogen derivative and allows non-invasive, repetitive imaging of the ER, mainly the α subtype. This technique has been validated for measurement of ER in breast cancer and it has been shown that lesions with no or limited reduction of 18F-FES uptake are at risk for early progression and thus therapy failure.

The relationship between the absolute value of the PET parameters, and their change between baseline and Week 4, will be correlated to treatment response and survival of the patients.

The hypothesis is that responding patients will have a median reduction of FES uptake on pre- and post-fulvestrant 18F-FES-PET (at Week 4) of \>75% (based on SUVmax). All patients with CR or PR according to RECIST will be classified as having responded to Fulvestrant treatment. The response rate is hypothesized to be higher in the 18F-FES responder group than in the 18F-FES non-responder group.

Core biopsies and blood from patients will be collected and stored in a biobank.

cf-DNA will be isolated from plasma and copy number alterations will be measured by shallow whole-exome sequencing.

DNA will be extracted form core biopsies and will be subject to ER/chromatin analysis, shallow whole-exome sequencing and targeted sequencing.

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

Clinical benefit is defined as the number of patients having complete response, partial response or stable disease, as determined by RECIST v1.1 criteria

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
FUlvestrant in Gynecological Cancers That Are Potentially Hormone Sensitive: the FUCHSia Study	NCT03926936	Endometrial Str... Adenosarcoma of... Leiomyosarcoma ... Endometrial Can... Sex Cord Stroma... Serous Ovarian ...	Fulvestrant	18 Years -	University Hospital, Gasthuisberg
FUlvestrant in Gynecological Cancers That Are Potentially Hormone Sensitive: the FUCHSia Study	NCT03926936	Endometrial Str... Adenosarcoma of... Leiomyosarcoma ... Endometrial Can... Sex Cord Stroma... Serous Ovarian ...	Fulvestrant	18 Years -	University Hospital, Gasthuisberg

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