Clinical trial • Phase III • Oncology

LETROZOLE for Low-grade serous epithelial ovarian cancer|Fallopian tube cancer|Primary peritoneal cancer

Phase III trial of LETROZOLE for Low-grade serous epithelial ovarian cancer|Fallopian tube cancer|Primary peritoneal cancer.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Low-grade serous epithelial ovarian cancer|Fallopian tube cancer|Primary peritoneal cancer
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
10-10-2024
First CTIS Authorization Date
09-12-2024

Trial design

Randomised, carboplatin (iv; max reported dose 450 mg/m2) and paclitaxel (iv; max reported dose 175 mg/m2) as standard chemotherapy comparator (combination carboplatin + paclitaxel); exact schedule details not specified in the ctis record.-controlled Phase III trial across 40 sites in Italy, Czechia.

Randomised
Yes
Comparator
Carboplatin (IV; max reported dose 450 mg/m2) and Paclitaxel (IV; max reported dose 175 mg/m2) as standard chemotherapy comparator (combination carboplatin + paclitaxel); exact schedule details not specified in the CTIS record.
Target Sample Size
142

Eligibility

Recruits 142 No vulnerable populations selected; only adults (Age ≥ 18) are eligible. Written informed consent must be obtained prior to any study-specific procedure. No mention of assent or specific procedures for minors..

Vulnerable Population
No vulnerable populations selected; only adults (Age ≥ 18) are eligible. Written informed consent must be obtained prior to any study-specific procedure. No mention of assent or specific procedures for minors.

Inclusion criteria

  • {"criterion_text":"- 1. Age ≥ 18 years.\n- 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.\n- 3. Immunohistochemically determined positivity (≥ 10%) for PgR and/or ER expression. This is to be confirmed by centralized review.\n- 4. Patients must have undergone an upfront surgery with maximal cytoreductive effort, with either optimal or suboptimal residual disease status.\n- 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.\n- 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.\n- 7. Randomization must take place within 90 days (preferably within 60 days) of primary cytoreductive surgery.\n- 8. Eastern Cooperative Oncology Group - performance status (ECOG-PS) 0-1.\n- 9. To be able to take oral medications\n- 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.\n- 11. Written informed consent obtained prior to any study-specific procedure."}

Exclusion criteria

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

Endpoints

Primary endpoints

  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"PFS defined as time from randomization to local/regional relapse (per RECIST v1.1 as noted in translation), distant metastasis, or death from any cause."}

Secondary endpoints

  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"ORR measured as percentage of patients with CR or PR per RECIST 1.1."}

Other endpoints

  • {"endpoint_text":"- to evaluate the response of tumor to letrozole compared with standard chemotherapy in terms of objective response rate (ORR);\n- To test the predictive effect of ER, PgR on response to letrozole in terms of PFS and ORR;\n- to evaluate the possible negative association between the effect of letrozole, in terms of PFS and ORR, and the proliferative index Ki67;\n- to evaluate the impact of letrozole compared with the impact of standard chemotherapy on patients’ health related quality of life evaluated by MENQOL;\n- to evaluate the impact of letrozole compared with standard chemotherapy on patients’ musculoskeletal pain evaluated by BPI-SF;\n- to describe the OS according to randomization arm.\n- to evaluate the safety of letrozole compared with standard chemotherapy.","definition_or_measurement_approach":"ORR per RECIST 1.1; predictive biomarkers ER/PgR assessed centrally (IHC); Ki67 proliferative index measured; quality of life measured by MENQOL instrument; musculoskeletal pain measured by BPI-SF; OS measured as overall survival by randomization arm; safety assessed by standard adverse event reporting."}

Recruitment

Planned Sample Size
142
Recruitment Window Months
69
Consent Approach
Written informed consent obtained from each participant prior to any study-specific procedure. Only adult participants (≥18 years) are eligible and provide consent. Subject information and ICF documents are available in Czech (e.g., L1_SIS and ICF_Main ICF_CZ_v1_14-FEB-2025 and other CZ documents) and Italian translations of the protocol/public title are present.

Geography

Total Number Of Sites
40
Total Number Of Participants
142

Italy

Earliest CTIS Part Ii Submission Date
30-09-2024
Latest Decision Or Authorization Date
29-04-2025
Processing Time Days
211
Number Of Sites
36
Number Of Participants
132

Sites

Site Name
Istituto Oncologico Veneto
Department Name
Oncology
Principal Investigator Name
Elvira Scelzi
Principal Investigator Email
elvira.scelzi@iov.veneto.it
Contact Person Name
Elvira Scelzi
Contact Person Email
elvira.scelzi@iov.veneto.it
Site Name
I.F.O. Istituti Fisioterapici Ospitalieri
Department Name
Oncology
Principal Investigator Name
Paola Malaguti
Principal Investigator Email
paola.malaguti@ifo.it
Contact Person Name
Paola Malaguti
Contact Person Email
paola.malaguti@ifo.it
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
Oncology
Principal Investigator Name
Giovanna Scarfone
Principal Investigator Email
giovanna.scarfone@policlinico.mi.it
Contact Person Name
Giovanna Scarfone
Site Name
Azienda Ospedaliero Universitaria Pisana
Department Name
Oncology
Principal Investigator Name
Stefania Cosio
Principal Investigator Email
stefania.cosio@gmail.com
Contact Person Name
Stefania Cosio
Contact Person Email
stefania.cosio@gmail.com
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
Ginecology
Principal Investigator Name
Dionyssios Katsaros
Principal Investigator Email
dkatsaros@cittadellasalute.to.it
Contact Person Name
Dionyssios Katsaros
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
Oncology
Principal Investigator Name
Fable Zustovich
Principal Investigator Email
fable.zustovich@aulss1.veneto.it
Contact Person Name
Fable Zustovich
Site Name
Azienda Socio Sanitaria Territoriale Lariana
Department Name
Oncology
Principal Investigator Name
Monica Giordano
Principal Investigator Email
monica.giordano@asst-lariana.it
Contact Person Name
Monica Giordano
Site Name
Ospedale San Raffaele S.r.l.
Department Name
Oncology
Principal Investigator Name
Luca Bocciolone
Principal Investigator Email
bocciolone.luca@hsr.it
Contact Person Name
Luca Bocciolone
Contact Person Email
bocciolone.luca@hsr.it
Site Name
Azienda USL Toscana Centro
Department Name
Oncology
Principal Investigator Name
Elena Zafarana
Principal Investigator Email
elena.zafarana@uslcentro.toscana.it
Contact Person Name
Elena Zafarana
Site Name
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
Oncoematolgy
Principal Investigator Name
Stefania Napolitano
Principal Investigator Email
stefania.napolitano@unicampania.it
Contact Person Name
Stefania Napolitano
Site Name
Azienda Unita' Locale Socio Sanitaria N. 2 Marca Trevigiana
Department Name
Oncology
Principal Investigator Name
Grazia Artioli
Principal Investigator Email
grazia.artioli@aulss2.veneto.it
Contact Person Name
Grazia Artioli
Site Name
Humanitas Mirasole S.p.A.
Department Name
Oncology
Principal Investigator Name
Domenica Lorusso
Principal Investigator Email
domenica.lorusso@hunimed.eu
Contact Person Name
Domenica Lorusso
Contact Person Email
domenica.lorusso@hunimed.eu
Site Name
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Department Name
Oncology
Principal Investigator Name
Germana Tognon
Principal Investigator Email
germanatognon@gmail.com
Contact Person Name
Germana Tognon
Contact Person Email
germanatognon@gmail.com
Site Name
Careggi University Hospital
Department Name
Oncology
Principal Investigator Name
Maria Cristina Petrella
Principal Investigator Email
mariacristina.petrella@gmail.com
Contact Person Name
Maria Cristina Petrella
Site Name
Azienda Sanitaria Universitaria Friuli Centrale
Department Name
Oncology
Principal Investigator Name
Claudia Andreetta
Principal Investigator Email
claudia.andreetta@asufc.sanita.fvg.it
Contact Person Name
Claudia Andreetta
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Oncology
Principal Investigator Name
Vanda Salutari
Principal Investigator Email
vanda.salutari@policlinicogemelli.it
Contact Person Name
Vanda Salutari
Site Name
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Department Name
Oncology
Principal Investigator Name
Violante Di Donato
Principal Investigator Email
violante.didonato@uniroma1.it
Contact Person Name
Violante Di Donato
Contact Person Email
violante.didonato@uniroma1.it
Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
Ginecology
Principal Investigator Name
Andrea Alberto Lissoni
Principal Investigator Email
andreaalberto.lissoni@unimib.it
Contact Person Name
Andrea Alberto Lissoni
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
Oncology
Principal Investigator Name
Chiara Cassani
Principal Investigator Email
Ch.Cassani@smatteo.pv.it
Contact Person Name
Chiara Cassani
Contact Person Email
Ch.Cassani@smatteo.pv.it
Site Name
Istituto Oncologico Veneto (Padova)
Department Name
Oncology
Principal Investigator Name
Valentina Guarneri
Principal Investigator Email
valentina.guarneri@unipd.it
Contact Person Name
Valentina Guarneri
Contact Person Email
valentina.guarneri@unipd.it
Site Name
Azienda Socio-Sanitaria Territoriale Del Garda
Department Name
Oncology
Principal Investigator Name
Anna Rizzi
Principal Investigator Email
anna.rizzi@asst-garda.it
Contact Person Name
Anna Rizzi
Contact Person Email
anna.rizzi@asst-garda.it
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
Oncology
Principal Investigator Name
Claudia Casanova
Principal Investigator Email
claudia.casanova@auslromagna.it
Contact Person Name
Claudia Casanova
Site Name
Istituto Europeo Di Oncologia S.r.l.
Department Name
Ginecology
Principal Investigator Name
Nicoletta Colombo
Principal Investigator Email
nicoletta.colombo@ieo.it
Contact Person Name
Nicoletta Colombo
Contact Person Email
nicoletta.colombo@ieo.it
Site Name
Azienda USL IRCCS Di Reggio Emilia
Department Name
Oncology
Principal Investigator Name
Alessandra Bologna
Principal Investigator Email
Alessandra.Bologna@ausl.re.it
Contact Person Name
Alessandra Bologna
Contact Person Email
Alessandra.Bologna@ausl.re.it
Site Name
Fondazione Poliambulanza
Department Name
Oncology
Principal Investigator Name
Chiara Abeni
Principal Investigator Email
chiara.abeni@poliambulanza.it
Contact Person Name
Chiara Abeni
Contact Person Email
chiara.abeni@poliambulanza.it
Site Name
Azienda Socio Sanitaria Territoriale Dei Sette Laghi
Department Name
Ginecology
Principal Investigator Name
Nicoletta Donadello
Principal Investigator Email
nicoletta.donadello@asst-settelaghi.it
Contact Person Name
Nicoletta Donadello
Site Name
Ente Ospedaliero Ospedali Galliera Di Genova
Department Name
Oncology
Principal Investigator Name
Andrea De Censi
Principal Investigator Email
andrea.decensi@galliera.it
Contact Person Name
Andrea De Censi
Contact Person Email
andrea.decensi@galliera.it
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Oncology
Principal Investigator Name
Alberto Farolfi
Principal Investigator Email
alberto.farolfi@irst.emr.it
Contact Person Name
Alberto Farolfi
Contact Person Email
alberto.farolfi@irst.emr.it
Site Name
Azienda Ospedaliero-Universitaria Di Cagliari
Department Name
Oncology
Principal Investigator Name
Elena Massa
Principal Investigator Email
emassa@medicina.unica.it
Contact Person Name
Elena Massa
Contact Person Email
emassa@medicina.unica.it
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Oncology
Principal Investigator Name
Francesco Raspagliesi
Principal Investigator Email
Francesco.Raspagliesi@istitutotumori.mi.it
Contact Person Name
Francesco Raspagliesi
Site Name
Azienda Unita' Sanitaria Locale Toscana Sud Est
Department Name
Oncology
Principal Investigator Name
Sabrina Del Buono
Principal Investigator Email
sabrina.delbuono@uslsudest.toscana.it
Contact Person Name
Sabrina Del Buono
Site Name
Azienda Socio Sanitaria Locale Della Provincia Di Biella
Department Name
Oncology
Principal Investigator Name
Laura Zavallone
Principal Investigator Email
laura.zavallone@aslbi.piemonte.it
Contact Person Name
Laura Zavallone

Czechia

Earliest CTIS Part Ii Submission Date
15-01-2025
Latest Decision Or Authorization Date
08-04-2026
Processing Time Days
448
Number Of Sites
4
Number Of Participants
10

Sites

Site Name
Vseobecna Fakultni Nemocnice V Praze
Department Name
Klinika gynekologie, porodnictví a neonatologie 1.LF UK a VFN v Praze
Principal Investigator Name
Michal Kníže
Principal Investigator Email
michal.knize@vfn.cz
Contact Person Name
Michal Kníže
Contact Person Email
michal.knize@vfn.cz
Site Name
Fakultni Nemocnice Bulovka
Department Name
Gynekologicko-porodnická klinika 1. LF UK a FN Bulovka
Principal Investigator Name
Michal Zikán
Principal Investigator Email
michal.zikan@bulovka.cz
Contact Person Name
Michal Zikán
Contact Person Email
michal.zikan@bulovka.cz
Site Name
Fakultni Nemocnice Kralovske Vinohrady
Department Name
Gynekologicko-porodnická klinika 3. LF UK a FNKV
Principal Investigator Name
Lukáš Rob
Principal Investigator Email
lukas.rob@fnkv.cz
Contact Person Name
Lukáš Rob
Contact Person Email
lukas.rob@fnkv.cz
Site Name
Fakultni Nemocnice V Motole
Department Name
Onkologická klinika 2.LF UK a FN Motol
Principal Investigator Name
Anna Nohejlová Medková
Principal Investigator Email
anna.nohejlova@fnmotol.cz
Contact Person Name
Anna Nohejlová Medková
Contact Person Email
anna.nohejlova@fnmotol.cz

Sponsor

Primary sponsor

Full Name
Ente Ospedaliero Ospedali Galliera Di Genova
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Italy

Third parties

  • {"country":"","full_name":"Sophos Biotech srl","duties_or_roles":"Monetary support / funder","organisation_type":""}
  • {"country":"","full_name":"Italian Association for Cancer Research (AIRC)","duties_or_roles":"Monetary support / funder","organisation_type":""}

Investigational products

Investigational Product Name
Letrix 2,5 mg compresse rivestite con film.
Active Substance
LETROZOLE
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL USE
Authorisation Status
Marketing authorisation: 040229027 (IT)
Starting Dose
2.5 mg (2500 µg)
Frequency
daily
Maximum Dose
2500 µg
Investigational Product Name
CARBOPLATIN
Active Substance
CARBOPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS USE
Starting Dose
450 mg/m2 (max reported)
Maximum Dose
450 mg/m2
Investigational Product Name
PACLITAXEL
Active Substance
PACLITAXEL
Modality
Small molecule
Routes Of Administration
INTRAVENOUS ADMINISTRATION
Route
INTRAVENOUS ADMINISTRATION
Starting Dose
175 mg/m2 (max reported)
Maximum Dose
175 mg/m2
Combination Treatment
Yes

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