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Carcinoma, Ovarian EpithelialPhase 3LEPRENCT05601700

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

A Phase 3 study testing Letrozole tablets and carboplatin AUC 5 and paclitaxel 175 mg/m2 in people with Carcinoma, Ovarian Epithelial and Low Grade Serous Adenocarcinoma of Ovary, run by Ente Ospedaliero Ospedali Galliera at 19 sites in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Letrozole tablets and carboplatin AUC 5 and paclitaxel 175 mg/m2
Could I receive a placebo?
No, everyone receives an active treatment
How many people
132 participants
Where
19 sitesItaly
Study dates
22 Sep 2022to 22 Sep 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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.

Trial locations and contacts

19 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Andrea DeCensi, Prof. contact

+39(0)105634501

andrea.decensi@galliera.it

Marianna Fava, PhD contact

+39(0)105634580

marianna.fava@galliera.it

19 sites in 1 country

Italy19 sites, 19 recruiting

  • Ospedale San Donato

    Arezzo, AR, 52100

    Sabrina Del Buono, MD

    Recruiting

  • Ospedale San Martino

    Belluno, BL, 32100

    Fable Zustovich, MD

    Recruiting

  • Fondazione Poliambulanza

    Brescia, BS, 25124

    Chiara Abeni, MD

    Recruiting

  • ASST degli Spedali Civili di Brescia

    Brescia, BS

    Germana Tognon

    Recruiting

  • IRCCS Istituto Oncologico Veneto

    Castelfranco Veneto, TV, 31033

    Simona Frezzini, MD

    Recruiting

  • Ospedale Sant'Anna

    Como, CO, 22042

    Monica Giordano, MD

    Recruiting

  • AOU Ferrara

    Ferrara, FE, 44124

    Antonio Frassoldati, Prof.

    Recruiting

  • Medical Oncology Division, Ente Ospedaliero Ospedali Galliera

    Genova, Genova, 16128

    Andrea De Censi, Prof., +390105634501, andrea.decensi@galliera.it

    Irene Maria Briata, Dr, +390105634504, irene.maria.briata@galliera.it

    Recruiting

  • IRST

    Meldola, FC, 47014

    Ugo De Giorgi, MD

    Recruiting

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, MI, 20133

    Francesco Raspagliesi, Prof.

    Recruiting

  • IEO

    Milan, MI, 20141

    Nicoletta Colombo, Prof.

    Recruiting

  • IRCCS Istituto Oncologico Veneto

    Padua, PD, 35128

    Valentina Guarneri, Prof.

    Recruiting

  • Ospedale degli Infermi

    Ponderano, BI, 13875

    Laura Zavallone, MD

    Recruiting

  • AUSL Romagna

    Rimini

    Claudia Casanova, MD

    Recruiting

  • IFO Regina Elena

    Roma, RM, 00144

    Paola Malaguti, MD

    Recruiting

  • Policlinico Umberto I

    Roma, RM, 00161

    Violante Di Donato

    Recruiting

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    Roma, RM, 00168

    Domenica Lorusso, Prof.

    Recruiting

  • Ospedale Ca' Foncello

    Treviso, TV, 31100

    Grazia Artioli, MD

    Recruiting

  • Ospedale Del Ponte

    Varese, VA, 21100

    Nicoletta Donadello, MD

    Recruiting

Other trials in Italy

About this study

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

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.

Read the detailed description

Primary objective:

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

Secondary objectives:

  • 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 and 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 Menopausal Quality of Life Questionnaire (MENQOL);
  • to evaluate the impact of letrozole compared with standard chemotherapy on patients' musculoskeletal pain evaluated by Brief Pain Inventory - Short Form (BPISF);
  • to evaluate the effect on overall survival (OS). As most patients will recur and will be switched to chemotherapy and vice versa, OS is not expected to be significantly different;
  • to evaluate the safety of letrozole compared with standard chemotherapy according to CTCAE v 5.0.

Translational objectives:

  • to characterize the mutational profile and gene expression of the disease by NGS (next-generation sequencing) methodology on tissue samples;
  • to evaluate the circulating tumor DNA (ctDNA) on liquid biopsies as a tool to monitor the disease response.
Being tested
Letrozole tablets, carboplatin AUC 5 and paclitaxel 175 mg/m2
Keywords
Estrogen/progesteron receptor positive tumor, Letrozole, Aromatase Inhibitors
Medical subject headings
Carcinoma, Ovarian Epithelial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Letrozole tabletsDrug

    ATC: L02BG04

  • carboplatin AUC 5 and paclitaxel 175 mg/m2Drug

    ATC: L01XA02 and ATC: L01CD01 respectively

Study groups in NCT05601700
Study groupRoleWhat they receive
Experimental armExperimentalLetrozole 2.5 mg daily, per os, until progression or up to 60 months, whichever comes first
Receives: Drug: Letrozole tablets
Control armActive comparatorCarboplatin AUC 5 + Paclitaxel 175 mg/mq, IV, on day 1 every 21 days, for 6-8 cycles.
Receives: Drug: carboplatin AUC 5 and paclitaxel 175 mg/m2

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 54 months up to 84 months

Secondary outcomes (5)

  1. Objective Response Rate (ORR)

    the percentage of patients with an objective response, i.e. patients who will experience a complete response (CR), or a partial response (PR) as determined by RECIST 1.1. Each patient will be assigned the best response ever recorded during the trial.

    Measured: 54 months up to 84 months

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

    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 according to ER and PgR % expression.

    Measured: 54 months up to 84 months

  3. Clinical Benefit (CB)

    the percentage of patients who will experience a CR or PR or stable disease (SD). Each patient will be assigned the best response ever recorded during the trial.

    Measured: 54 months up to 84 months

  4. Overall survival (OS)

    the time from the date of randomization to the date of death from any cause. Patients not reported as having died at the end of the study will be censored at the date they were last known to be alive.

    Measured: 54 months up to 84 months

  5. Safety (Adverse Events)

    Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE

    Measured: 54 months up to 84 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2022
  2. Study start22 Sep 2022
  3. Primary completion22 Sep 2029 (estimated)
  4. Study completion22 Sep 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Parallel Assignment
Masking
None (open label)
Enrolment
132 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05601700
Sponsor's protocol ID
10UCS2018
Other IDs
2020-003066-39
Acronym
LEPRE
Status last verified
Jan 2025
First submitted
21 Oct 2022
Last updated
27 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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. 2026 Feb;112(1):67-74. doi: 10.1177/03008916251395596. Epub 2025 Dec 14.

    PubMed 41392465

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Letrozole tablets and carboplatin AUC 5 and paclitaxel 175 mg/m2 in people with Carcinoma, Ovarian Epithelial and Low Grade Serous Adenocarcinoma of Ovary, run by Ente Ospedaliero Ospedali Galliera at 19 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Andrea DeCensi, Prof. (+39(0)105634501, andrea.decensi@galliera.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: 54 months up to 84 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05601700, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2025.

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