Trial Title:
Letrozole for Estrogen/Progesterone Receptor Positive Low-grade Serous Epithelial Ovarian Cancer (LEPRE Trial)
NCT ID:
NCT05601700
Condition:
Carcinoma, Ovarian Epithelial
Low Grade Serous Adenocarcinoma of Ovary
Conditions: Official terms:
Carcinoma, Ovarian Epithelial
Cystadenocarcinoma, Serous
Paclitaxel
Carboplatin
Letrozole
Conditions: Keywords:
Estrogen/progesteron receptor positive tumor
Letrozole
Aromatase Inhibitors
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Letrozole tablets
Description:
ATC: L02BG04
Arm group label:
Experimental arm
Intervention type:
Drug
Intervention name:
carboplatin AUC 5 and paclitaxel 175 mg/m2
Description:
ATC: L01XA02 and ATC: L01CD01 respectively
Arm group label:
Control arm
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.
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.
Criteria for eligibility:
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.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ospedale San Donato
Address:
City:
Arezzo
Zip:
52100
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Sabrina Del Buono, MD
Facility:
Name:
Ospedale degli Infermi
Address:
City:
Ponderano
Zip:
13875
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Laura Zavallone, MD
Facility:
Name:
Ospedale San Martino
Address:
City:
Belluno
Zip:
32100
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Fable Zustovich, MD
Facility:
Name:
Fondazione Poliambulanza
Address:
City:
Brescia
Zip:
25124
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Chiara Abeni, MD
Facility:
Name:
ASST degli Spedali Civili di Brescia
Address:
City:
Brescia
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Germana Tognon
Facility:
Name:
Ospedale Sant'Anna
Address:
City:
Como
Zip:
22042
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Monica Giordano, MD
Facility:
Name:
IRST
Address:
City:
Meldola
Zip:
47014
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Ugo De Giorgi, MD
Facility:
Name:
AOU Ferrara
Address:
City:
Ferrara
Zip:
44124
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Antonio Frassoldati, Prof.
Facility:
Name:
Fondazione IRCCS Istituto Nazionale dei Tumori
Address:
City:
Milan
Zip:
20133
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Francesco Raspagliesi, Prof.
Facility:
Name:
IEO
Address:
City:
Milan
Zip:
20141
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Nicoletta Colombo, Prof.
Facility:
Name:
IRCCS Istituto Oncologico Veneto
Address:
City:
Padua
Zip:
35128
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Valentina Guarneri, Prof.
Facility:
Name:
IFO Regina Elena
Address:
City:
Roma
Zip:
00144
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Paola Malaguti, MD
Facility:
Name:
Policlinico Umberto I
Address:
City:
Roma
Zip:
00161
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Violante Di Donato
Facility:
Name:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Address:
City:
Roma
Zip:
00168
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Domenica Lorusso, Prof.
Facility:
Name:
IRCCS Istituto Oncologico Veneto
Address:
City:
Castelfranco Veneto
Zip:
31033
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Simona Frezzini, MD
Facility:
Name:
Ospedale Ca' Foncello
Address:
City:
Treviso
Zip:
31100
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Grazia Artioli, MD
Facility:
Name:
Ospedale Del Ponte
Address:
City:
Varese
Zip:
21100
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Nicoletta Donadello, MD
Facility:
Name:
Medical Oncology Division, Ente Ospedaliero Ospedali Galliera
Address:
City:
Genova
Zip:
16128
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Andrea De Censi, Prof.
Phone:
+390105634501
Email:
andrea.decensi@galliera.it
Contact backup:
Last name:
Irene Maria Briata, Dr
Phone:
+390105634504
Email:
irene.maria.briata@galliera.it
Investigator:
Last name:
Andrea DeCensi
Email:
Principal Investigator
Investigator:
Last name:
Nicoletta Provinciali
Email:
Sub-Investigator
Facility:
Name:
AUSL Romagna
Address:
City:
Rimini
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Claudia Casanova, MD
Start date:
September 22, 2022
Completion date:
September 22, 2029
Lead sponsor:
Agency:
Ente Ospedaliero Ospedali Galliera
Agency class:
Other
Collaborator:
Agency:
Istituto Di Ricerche Farmacologiche Mario Negri
Agency class:
Other
Collaborator:
Agency:
Humanitas Hospital, Italy
Agency class:
Other
Source:
Ente Ospedaliero Ospedali Galliera
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05601700
