Letrozole for Estrogen/Progesterone Receptor positive low-grade serous Epithelial ovarian cancer. A randomized phase III trial. LEPRE Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ente Ospedaliero Ospedali Galliera Di Genova

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Dec 2024 → ongoing

Decision date (initial)

2026-04-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Sophos Biotech srl · Italian Association for Cancer Research (AIRC)

External identifiers

EU CT number

2024-516874-31-00

EudraCT number

2020-003066-39

ClinicalTrials.gov

NCT05601700

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective is to determine if letrozole is superior to standard chemotherapy in terms of progression-free survival (PFS) in patients with advanced
low-grade serous epithelial ovarian carcinoma positive for estrogen and/or progesterone receptors.

Secondary objectives 1

1. • to evaluate the response of tumor to letrozole compared with standard chemotherapy in terms of objective response rate (ORR); • To test the predictive effect of ER, PgR on response to letrozole in terms of PFS and ORR; • to evaluate the possible negative association between the effect of letrozole, in terms of PFS and ORR, and the proliferative index Ki67; • to evaluate the impact of letrozole compared with the impact of standard chemotherapy on patients’ health related quality of life evaluated by MENQOL; • to evaluate the impact of letrozole compared with standard chemotherapy on patients’ musculoskeletal pain evaluated by BPI-SF; • to describe the OS according to randomization arm. • to evaluate the safety of letrozole compared with standard chemotherapy.

Conditions and MedDRA coding

Patients with a low-grade serous epithelial carcinoma of the ovary (LGSCO) including cancer of fallopian tube and peritoneum, FIGO III-IV stage and with ER+ and/or PgR+ after primary surgery are eligible.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Age ≥ 18 years. 2. Newly diagnosed, low-grade serous carcinoma of the ovary including cancer of fallopian tube and peritoneum (invasive micropapillary serous carcinoma or invasive grade 1 serous carcinoma). This is to be confirmed via nuclear p53 immunohistochemistry testing by a central pathology review performed at the Coordinating Centre. 3. Immunohistochemically determined positivity (≥ 10%) for PgR and/or ER expression. This is to be confirmed by centralized review. 4. Patients must have undergone an upfront surgery with maximal cytoreductive effort, with either optimal or suboptimal residual disease status. 5. Stage III-IV according to 2018 FIGO classification. Furthermore, for a proper baseline evaluation patients must have undergone contrast-enhanced CT-scan of the chest, abdomen and pelvis within 28 days prior to randomization. If CT-scan is not recommended (e.g. for allergy to contrast agent) MRI or 18F-FDG PET/CT-scan are allowed. The imaging evaluation must be accompanied by an anamnestic and physical examination within 14 days prior to randomization. 6. Postmenopausal, defined as any of the following criteria: - Patients who underwent bilateral salpingo-oophorectomy; - Monolateral salpingo-oophorectomy, amenorrhea for 12 or more consecutive months and age ≥60 years; - Monolateral salpingo-oophorectomy, amenorrhea for 12 or more consecutive months, age <60 years and plus FSH and serum estradiol levels within the laboratory’s reference ranges for postmenopausal women. 7. Randomization must take place within 90 days (preferably within 60 days) of primary cytoreductive surgery. 8. Eastern Cooperative Oncology Group - performance status (ECOG-PS) 0-1. 9. To be able to take oral medications 10. Adequate bone marrow, hepatic and renal functions as defined below: - Absolute neutrophil count (ANC) ≥ 1500/mm3 - Platelets ≥ 100,000/mm3 - Hemoglobin ≥ 10.0 g/dL - Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) - ALT and AST ≤ 3.0 x ULN - Alkaline phosphatase ≤ 2.5 x ULN - Albumin ≥ 2.8 g/dL - Serum creatinine ≤ 1.5 x ULN. 11. Written informed consent obtained prior to any study-specific procedure.

Exclusion criteria 1

1. 1. Other malignancy within the last 5 years, except for non-melanoma skin cancer adequately treated. 2. Neoadjuvant chemotherapy or radiotherapy for the treatment of this disease. 3. Previous hormonal therapy for the treatment of this disease. 4. Known hypersensitivity to letrozole or known hypersensitivity/intolerance to carboplatin/paclitaxel therapy. 5. Active or uncontrolled systemic infection. 6. Known central nervous system metastases. 7. Severe cardiac disease, such as myocardial infarction or unstable angina within 6 months prior to randomization. 8. New York Heart Association (NYHA) Class III or greater congestive heart failure. 9. Neuropathy grade 2 or higher. 10. History of fractures of the spine or femur not properly treated. 11. Known osteoporosis (dual-energy x-ray absorptiometry (DEXA) of the femoral neck T score of −2.5 or lower) not adequately treated with bisphosphonates or RANKL inhibitors. 12. Concomitant use of inducers of CYP3A4 (e.g. phenytoin, rifampicin, carbamazepine, phenobarbital, and St. John’s Wort) which may reduce exposure to letrozole. Concomitant use of medicinal products with a narrow therapeutic index that are substrates for CYP2C19 (e.g. phenytoin, clopidrogel) that may have their systemic serum concentrations altered by letrozole. 13. Concurrent severe medical problems or any condition that would significantly limit full compliance with the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is PFS, defined for each patient as the time from the date of randomization to the date of local or regional relapse, distant metastasis, or death from any cause, whichever comes first.

Secondary endpoints 1

1. Objective Response Rate (ORR), defined as the percentage of patients with an objective response determined by a complete response (CR) or a partial response (PR) as determined by RECIST 1.1.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ente Ospedaliero Ospedali Galliera Di Genova

Sponsor organisation

Ente Ospedaliero Ospedali Galliera Di Genova

Address

Mura Delle Cappuccine 14

City

Genoa

Postcode

16128

Country

Italy

Scientific contact point

Organisation

Ente Ospedaliero Ospedali Galliera Di Genova

Contact name

Head of Oncology Division and Medicine Department

Public contact point

Organisation

Ente Ospedaliero Ospedali Galliera Di Genova

Contact name

Clinical Trial Information Oncology Division and Medicine Department

Locations

2 EU/EEA countries · 40 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications