E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
endometrial stromal sarcoma uterine adenosarcoma endometrial carcinoma sex cord stromal tumors serous ovarian cancer |
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E.1.1.1 | Medical condition in easily understood language |
endometrial stromal sarcoma uterine adenosarcoma endometrial carcinoma sex cord stromal tumors serous ovarian cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the response rate (RR) upon Fulvestrant treatment, comprising either partial or complete response, as determined by RECIST v1.1 criteria, in each tumor type group |
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E.2.2 | Secondary objectives of the trial |
• To determine progression-free survival (PFS) upon Fulvestrant treatment, after 3 years, in each tumor type group • To assess duration of response in each tumor type group • To assess safety and tolerability of Fulvestrant administration in each tumor type group • To assess quality of life (QoL) and symptoms in each tumor type group
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (LGESS, LGAS without sarcomatous overgrowth and LGLMS), 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 1 prior line of hormonal therapy (tamoxifen, progestins and/or aromatase inhibitors) ECOG performance status: 0-2 Demonstrate adequate organ function: creatinine ≤1.5 X upper limit of normal (ULN), serum total bilirubin ≤ 1.5 X ULN, AST (SGOT) and ALT (SGPT) < 5 X ULN 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Response rate (RR) upon Fulvestrant treatment in each tumor type group for the total number of patients from both the exploratory and confirmation cohort (interim analysis planned at Week 24), as determined by RECIST v1.1 criteria and assessed by computer tomography (CT) scans |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Progression-free survival (PFS) at 3 years in each tumor type group • Overall survival (OS) • Time to progression (TTP) • Clinical benefit rate (CBR) (CR + PR + stable disease [SD], SD of any duration) at interim analysis (IA, Week 24) and after 3 years, for each tumor type group • Safety and tolerability of Fulvestrant administration in each tumor type group • Change from baseline in QoL scores, as assessed by questionnaires EQ-5D and EORTC QLQ-C30 at the time of inclusion, at the end of the treatment and during follow-up
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PFS: at 3 years OS: at time of death Time to progression: at time of diagnosis of progressive disease Clinical benefit rate: every 3 months Safety and tolerability: every 3 months QoL: every 3 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
groups with different tumor types |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |