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

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 stromalsarcoma, low grade adenosarcoma without sarcomatous overgrowth and low gradeleiomyosarcoma), 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 scoringsystem (based on intensity and percentage of positive cells, see Appendix 4), andarchival tissue available

• At least and maximum of 1 prior line of hormonal therapy (tamoxifen, progestinsand/or aromatase inhibitors). Response on 1st line hormonal therapy must have lastedfor 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 maybe included in the study), alanine transaminase or aspartate transaminase < 2.5x ULNif 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 andsatisfying the following criteria: amenorrhea for at least 12 months and FSH inpostmenopausal range, or (iii) ≥ 18 years of age and having had a bilateraloophorectomy

• 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 bea too high burden for their physical conditions; (ii) patients who receivedtamoxifen within 8 weeks prior to study Day 1. These patients will be enrolled, butthey 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 5years, except for adequately treated squamous or basal cell carcinoma of the skin orin situ cervical carcinoma

• Patients currently receiving (and unwilling to discontinue) any estrogen replacementtherapy.

• Patients participating in a study or having participated in a study of aninvestigational 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 studyDay 1 or who has not recovered from adverse events (i.e., adverse event not resolvedto ≤ Grade 1 or baseline), due to a previously administered agent

• Patients with no archival tissue available, except for patients from whom anadditional fresh core biopsy can be obtained for ER assessment

• Any other disease, metabolic dysfunction, physical examination or clinicallaboratory finding that, in the investigator's opinion, gives reasonable suspicionof 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 fromtreatment complications or interfere with obtaining informed consent.

• Any condition not permitting compliance with the study protocol