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Letrozole treatment for low-grade serous ovarian cancer

Letrozole for Estrogen/Progesterone Receptor Positive Low-grade Serous Epithelial Ovarian Cancer: a Randomized Phase III Trial (LEPRE Trial)

Phase 3 Interventional Ente Ospedaliero Ospedali Galliera · NCT05601700

This study is testing if the drug Letrozole can help people with low-grade serous ovarian cancer live longer and feel better compared to standard chemotherapy.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment132 (estimated)
Ages18 Years and up
SexFemale
SponsorEnte Ospedaliero Ospedali Galliera Academic / other
Drugs / interventionschemotherapy
Locations19 sites (Arezzo, AR and 18 other locations)
Trial IDNCT05601700 on ClinicalTrials.gov

What this trial studies

This phase III trial evaluates the effectiveness of Letrozole compared to standard chemotherapy in patients with hormone receptor positive low-grade serous epithelial ovarian carcinoma. The study aims to determine if Letrozole can significantly prolong progression-free survival (PFS) and improve quality of life compared to carboplatin and paclitaxel. It includes a multicenter approach across various hospitals in Italy and incorporates translational objectives to analyze tumor characteristics through next-generation sequencing. The trial will also assess safety and response rates to the treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with newly diagnosed low-grade serous carcinoma of the ovary that is hormone receptor positive.

Not a fit: Patients with non-hormone receptor positive tumors or those with earlier stage disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective and less toxic option for patients with low-grade serous ovarian cancer.

How similar studies have performed: Previous studies have shown promise in using hormonal therapies for similar conditions, but this specific approach with Letrozole is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

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
* 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.

I - 11. Written informed consent obtained prior to any study-specific procedure.

Exclusion Criteria:

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.

Where this trial is running

Arezzo, AR and 18 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Carcinoma, Ovarian EpithelialLow Grade Serous Adenocarcinoma of OvaryEstrogen/progesteron receptor positive tumorLetrozoleAromatase Inhibitors
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.