Letrozole for Estrogen/Progesterone Receptor Positive Low-grade Serous Epithelial Ovarian Cancer (LEPRE Trial)

NCT05601700 | Recruiting Phase 3 DMC

• 2 other identifiers: 10UCS20182020-003066-39
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 19

Brief Summary

This is an Italian, multicenter, randomized, open-label phase III trial which will evaluate if Letrozole is superior to standard adjuvant chemotherapy in patients with hormone receptor positive low-grade serous epithelial carcinoma of the ovary (LGSCO). The hypothesis is that letrozole will significantly prolong median progression free survival (PFS) compared with the standard chemotherapy treatment, namely carboplatin AUC 5 and paclitaxel 175 mg/m2.

Conditions

Carcinoma, Ovarian Epithelial; Low Grade Serous Adenocarcinoma of Ovary

Keywords

Estrogen/progesteron receptor positive tumor; Letrozole; Aromatase Inhibitors

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  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. Patients not recurred, not progressed or not died while on study or patients lost to f-up will be censored at their last disease assessment date.

  54 months up to 84 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  54 months up to 84 months

• Predictive effect of ER and PgR (% expression) on response to letrozole in terms of PFS and ORR

  54 months up to 84 months

• Clinical Benefit (CB)

  54 months up to 84 months

• Overall survival (OS)

  54 months up to 84 months

• Safety (Adverse Events)

  54 months up to 84 months

Other Outcomes (3)

• Translational Objective 1

  54 months up to 84 months

• Translational Objective 2

  54 months up to 84 months

• Translational Objective 3

  54 months up to 84 months

Study Arms (2)

Experimental arm

EXPERIMENTAL

Letrozole 2.5 mg daily, per os, until progression or up to 60 months, whichever comes first

Drug: Letrozole tablets

Control arm

ACTIVE COMPARATOR

Carboplatin AUC 5 + Paclitaxel 175 mg/mq, IV, on day 1 every 21 days, for 6-8 cycles.

Drug: carboplatin AUC 5 and paclitaxel 175 mg/m2

Interventions

Letrozole tablets DRUG

ATC: L02BG04

Experimental arm

carboplatin AUC 5 and paclitaxel 175 mg/m2 DRUG

ATC: L01XA02 and ATC: L01CD01 respectively

Control arm

Eligibility Criteria

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

You may qualify if:

• I - 1. Age ≥ 18 years. I - 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.
• I - 3. Immunohistochemically determined positivity (≥ 10%) for ER and/or PgR expression. This is to be confirmed by centralized review.
• I - 4. Patients must have undergone an upfront surgery with maximal cytoreductive effort, with either optimal or suboptimal residual disease status.
• I - 5. Stage III-IV according to 2018 FIGO classification. For proper staging:
• 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.
• I - 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 FSH and serum estradiol levels within the laboratory's reference ranges for post-menopausal women.
• I - 7. Randomization must take place within 60 days of primary cytoreductive surgery.
• I - 8. Eastern Cooperative Oncology Group - performance status (ECOG-PS) 0-1.
• I - 9. To be able to take oral medications.
• I - 10. Adequate bone marrow, hepatic and renal functions as defined below:
• Absolute neutrophil count (ANC) ≥ 1500/mm3

You may not qualify if:

• E - 1. Other malignancy within the last 5 years, except for non-melanoma skin cancer adequately treated.
• E - 2. Neoadjuvant chemotherapy or radiotherapy for the treatment of this disease.
• E - 3. Previous hormonal therapy for the treatment of this disease.
• E - 4. Known hypersensitivity to letrozole or known hypersensitivity/intolerance to carboplatin/paclitaxel therapy.
• E - 5. Active or uncontrolled systemic infection.
• E - 6. Known central nervous system metastases.
• E - 7. Severe cardiac disease, such as myocardial infarction or unstable angina within 6 months prior to randomization.
• E - 8. New York Heart Association (NYHA) Class III or greater congestive heart failure.
• E - 9. Neuropathy grade 2 or higher.
• E - 10. History of fractures of the spine or femur not properly treated.
• E - 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.
• E - 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.
• E - 13. Concurrent severe medical problems or any condition that would significantly limit full compliance with the study.

Sponsors & Collaborators

• Ente Ospedaliero Ospedali Galliera: lead
• Istituto Di Ricerche Farmacologiche Mario Negri: collaborator
• Humanitas Hospital, Italy: collaborator

Study Sites (19)

Ospedale San Donato

Arezzo, AR, 52100, Italy

RECRUITING

Ospedale degli Infermi

Ponderano, BI, 13875, Italy

RECRUITING

Ospedale San Martino

Belluno, BL, 32100, Italy

RECRUITING

Fondazione Poliambulanza

Brescia, BS, 25124, Italy

RECRUITING

ASST degli Spedali Civili di Brescia

Brescia, BS, Italy

RECRUITING

Ospedale Sant'Anna

Como, CO, 22042, Italy

RECRUITING

IRST

Meldola, FC, 47014, Italy

RECRUITING

AOU Ferrara

Ferrara, FE, 44124, Italy

RECRUITING

Medical Oncology Division, Ente Ospedaliero Ospedali Galliera

Genova, Genova, 16128, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, MI, 20133, Italy

RECRUITING

IEO

Milan, MI, 20141, Italy

RECRUITING

IRCCS Istituto Oncologico Veneto

Padua, PD, 35128, Italy

RECRUITING

IFO Regina Elena

Roma, RM, 00144, Italy

RECRUITING

Policlinico Umberto I

Roma, RM, 00161, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, RM, 00168, Italy

RECRUITING

IRCCS Istituto Oncologico Veneto

Castelfranco Veneto, TV, 31033, Italy

RECRUITING

Ospedale Ca' Foncello

Treviso, TV, 31100, Italy

RECRUITING

Ospedale Del Ponte

Varese, VA, 21100, Italy

RECRUITING

AUSL Romagna

Rimini, Italy

RECRUITING

Related Publications (1)

• Carbone A, Biagioli E, Salutari V, Lorusso D, Provinciali N, Bocciolone L, Artioli G, Abeni C, Colombo N, De Giorgi U, Guarneri V, Cassani C, Scarfone G, Zavallone L, Donadello N, Donato VD, Giordano M, Scelzi E, Tognon G, Petrella MC, D'Incalci M, Marchini S, Dang HT, Alvisi MF, Corradengo D, Buttiron Webber T, Paleari L, Briata IM, Rutigliani M, Oliva M, Rulli E, DeCensi A. Letrozole for hormone receptor-positive low-grade ovarian cancer: Preliminary toxicity results of a phase III trial. Tumori. 2025 Dec 14:3008916251395596. doi: 10.1177/03008916251395596. Online ahead of print.

  PMID: 41392465 DERIVED

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial

Interventions

Letrozole; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Andrea DeCensi, MD

  E.O.Ospedali Galliera

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea DeCensi, Prof.

CONTACT

+39(0)105634501; andrea.decensi@galliera.it

Marianna Fava, PhD

CONTACT

+39(0)105634580; marianna.fava@galliera.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncology Director

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: October 21, 2022
• First Posted: November 1, 2022
• Study Start: September 22, 2022
• Primary Completion (Estimated): September 22, 2029
• Study Completion (Estimated): September 22, 2029
• Last Updated: January 27, 2025

Record last verified: 2025-01

Locations

IT (19)