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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04460807
Other study ID # 56UCS2017
Secondary ID 2018-000693-30
Status Terminated
Phase Phase 3
First received
Last updated
Start date February 13, 2020
Est. completion date April 27, 2023

Study information

Verified date February 2024
Source Ente Ospedaliero Ospedali Galliera
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

In this Italian, multicenter, randomized, double-blind, placebo controlled, phase III study the efficacy of exemestane will be evaluated in addition to the standard front line treatment in patients with hormone-receptor-positive high grade serous or endometrioid Epithelian Ovarian Cancer (EOC). The patients enrolled in the EXPERT trial will receive exemestane or placebo in addition to standard treatment. Patients and investigators will be blinded to study treatment. The hypothesis underlying the proposed clinical trial is that exemestane added to standard first line therapy will significantly prolong median progression free survival (PFS).


Description:

Estrogen and Progesterone play a role in promoting EOC growth, metastasis, and progression. Recent data show that ER and PgR expression is frequent in high grade EOC and has prognostic significance. A large meta-analysis showed a clinical benefit with any endocrine treatment, and in particular for aromatase inhibitors (AIs), with a greatere benefit for ER+ and/or PgR+ patients and platinum sensitive tumors. Moreover, the analysis of a few randomized clinical trials (RCTs) showed a reduced mortality with endocrine therapy in EOC, suggesting that ER and PgR have a predictive role and that inhibition of their activation could therefore be a treatment option for EOC. Exemestane is a well-tolerated and effective AI in endocrine sensitive breast cancer which inhibits the production of Estrogens by the adipose tissue in postmenopausal women. In this Italian, multicentre, randomized, double-blind, placebo controlled, phase III study will be assessed the efficacy of exemestane versus placebo in addition to the standard front line treatment in patients with high grade serous or endometrioid EOC, IHC positive (≥ 10%) ER or PgR disease, stage IIB - IV according to the FIGO classification. The primary objective of the study is to test the superiority of exemestane over placebo in addition to the standard front line treatment in terms of PFS. Secondary Objectives are: 1. to test whether the percent expression of ER and PgR is predictive of the effect of exemestane on PFS; 2. to test whether the addition of exemestane to the standard front line treatment can prolong Overall Survival (OS); 3. to evaluate objective response rate Overall Response Rate (ORR) of experimental treatment compared with the standard one; 4. to assess whether the effect of exemestane is affected by the proliferative index Ki67; 5. to evaluate the effect of exemestane on Quality of Life (QoL); 6. to evaluate the compliance to the study treatment; 7. to evaluate the safety profile of the experimental treatment compared with the standard one. Study design: a total of 468 subjects (234 per Arm) will be randomized in a 1:1 ratio to receive either standard chemotherapy treatment plus exemestane (Experimental arm) or standard chemotherapy plus placebo (Control arm). Exemestane/placebo will be self-administered as a single oral tablet of 25 mg/day until disease progression, unacceptable toxicity or physician/patient decision to withdraw, whichever comes first. Radiological disease assessments and CA125 will be performed at baseline and every 4 months from randomization, until end of study or disease progression whichever comes first. Safety assessments will be performed at each cycle during standard chemotherapy treatment, then at each study visit, up to 30 days after the last Experimental Treatment administration.Quality of Life will be assessed by a menopause-specific questionnaire, administered to patients at baseline (T0), at 12 months (T1) and at disease progression (T2). For patients who have signed the specific informed consent, tissues and blood samples will be collected.


Recruitment information / eligibility

Status Terminated
Enrollment 23
Est. completion date April 27, 2023
Est. primary completion date April 27, 2023
Accepts healthy volunteers No
Gender Female
Age group 18 Years and older
Eligibility Inclusion Criteria: - Age =18 years - Citologically or histologically confirmed high grade serous or endometrial epithelial ovarian cancer, including cancer of fallopian tube and peritoneum. For patients who are candidates for neoadjuvant chemotherapy, diagnosis must be documented via imaging or a core tissue (not fine needle aspiration) biopsy. - Disease stage IIB to IV according to FIGO classification. For patients who are candidates for neoadjuvant chemotherapy, stage IIB-IV should be documented via imaging or a core tissue (not fine needle aspiration) biopsy. - Patients must have completed a surgical debulking procedure, or be candidates for neoadjuvant chemotherapy. For patients enrolling after debulking surgery, randomization should occur at a maximum of 12 weeks and not before 4 weeks after surgery. - Immunoistochemically determined positivity (= 10%) for Progesterone and/or Estrogen receptor expression, including determination on cytology smears from ascitic fluid if surgery is differed. - Measurable or evaluable disease confirmed by radiological imaging, or histological proven ovarian cancer in the absence of postoperatively measurable or evaluable lesions - Eastern Cooperative Oncology Group - performance status (ECOG-PS) 0-2. - Written, informed consent obtained prior to any study-specific procedures. Exclusion Criteria: - Previous systemic therapy for ovarian cancer. - Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer. - Inadequate bone marrow, hepatic or renal functions, assessed within 7 days prior to randomization. - Treatment with hormonal contraceptives during the previous 3 months from diagnosis. - Concurrent comorbidities, which contraindicates the administration of chemotherapy, or endocrine therapy. - Pregnant or lactating patients. - Inability or unwillingness to swallow tablets.

Study Design


Intervention

Drug:
Exemestane
Exemestane in addition to standard therapy, in Experimental arm.
Other:
Placebo oral tablet
Placebo in addition to standard therapy, in Control arm.

Locations

Country Name City State
Italy Azienda Sanitaria Locale CN2 Alba CN
Italy AO SS Antonio e Biagio e Cesare Arrigo Alessandria AL
Italy CRO Centro di Riferimento Oncologico Aviano PN
Italy Ospedale Oncologico IRCCS Bari Bari BA
Italy Ospedale degli Infermi Biella BI
Italy Azienda Ospedaliero Universitaria Policlinico S.Orsola-Malpighi Bologna BO
Italy ASST degli Spedali Civili di Brescia Brescia BS
Italy Fondazione Poliambulanza Brescia BS
Italy AOU Cagliari, Policlinico Universitario Cagliari CA
Italy Fondazione del Piemonte per l'Oncologia - IRCCS Candiolo TO
Italy ARNAS Garibaldi Catania CT
Italy Azienda Ospedaliera per l'emergenza Cannizzaro Catania CT
Italy Ospedale Policlinico "SS. Annunziata" Chieti CH
Italy Ospedale Sant Anna di Como Como CO
Italy Azienda Ospedaliera S.Croce e Carle Cuneo CN
Italy Ospedale "degli Infermi" Faenza RA
Italy AULSS 1 Dolomiti - Ospedale "Santa Maria del Prato" Feltre BL
Italy ASL 3 Ospedale Villa Scassi Genova GE
Italy IRCCS AOU San Martino - IST Genova GE
Italy Medical Oncology Division, Ente Ospedaliero Ospedali Galliera Genova
Italy Ospedale "Vito Fazzi" Lecce LE
Italy ASST Lecco - Ospedale "A. Manzoni" Lecco LC
Italy Ospedale "Umberto I" Lugo RA
Italy Presidio Ospedaliero Unico Av3 Macerata MC
Italy Ospedale di Manerbio Manerbio BS
Italy Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Meldola FC
Italy Istituto Europeo di Oncologia (IEO) Milano MI
Italy AOU Policlinico di Modena Modena MO
Italy Ospedale di Mondovì CN1 Mondovì CN
Italy UOS Oncologia Ginecologica, Ospedale S. Gerardo Monza MB
Italy Istituto Nazionale Tumori - IRCCS "Fondazione G.Pascale" Napoli
Italy Azienda Ospedaliero-Universitaria Maggiore della Carità Novara
Italy A.R.N.A.S. Ospedali Civico Di Cristina Benfratelli Palermo PA
Italy Fondazione IRCCS Policlinico San Matteo Pavia PV
Italy Ospedale "Guglielmo da Saliceto" Piacenza PC
Italy Azienda Ospedaliero-Universitaria Pisana Pisa PI
Italy Azienda Ospedaliera Regionale San Carlo Potenza PZ
Italy Ospedale Santa Maria delle Croci Ravenna RA
Italy Azienda Ospedaliera Arcispedale Santa Maria Nuova Reggio Emilia RE
Italy Policlinico Umberto I, Università di Roma "La Sapienza" Roma RM
Italy Policlinico Universitario Fondazione Agostino Gemelli Roma RM
Italy Ospedale Casa Sollievo della Sofferenza San Giovanni Rotondo FG
Italy Azienda Ospedaliero Universitaria di Sassari Sassari SS
Italy ASST Valtellina e Alto Lario Sondrio SO
Italy AO Ordine Mauriziano Torino TO
Italy Azienda Ospedaliero-Universitaria Città della Salute e della Scienza - Ospedale Ostetrico Ginecologico Sant'Anna Torino TO
Italy Presidio Ospedaliero S. Andrea Vercelli VC

Sponsors (4)

Lead Sponsor Collaborator
Ente Ospedaliero Ospedali Galliera Federation of Italian Cooperative Oncology Groups, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Istituto Di Ricerche Farmacologiche Mario Negri

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Other Circulating and tissue biomarkers To collect and store blood and tissue samples to create a bio-bank for the assessment of circulating and tissue biomarkers with potentially prognostic/predictive value, including the androgen receptor (AR) expression and the generation of a somatic genomic and transcriptomic atlas of epithelial ovarian cancers, to map the different molecular vulnerabilities lagging behind the single definition of each histological subtype. Data generated will allow to select molecular biomarkers with prognostic/predictive relevance, to have information of patients risk of relapse or to guide novel treatment approaches.
These biomarker endpoints will be considered in a second phase of the study, if additional funds are available to perform the analyses.
Up to 20 months
Primary Progression free survival (PFS) PFS id defined for each patient as the time from the date of randomization to the date of local or regional relapse, distant metastasis, second primary malignancy or death from any cause, whichever comes first. Patients not recurred, progressed or died while on study or lost to follow-up will be censored at their last disease assessment date. Up to 20 months
Secondary Overall survival (OS) OS is defined for each patient as 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. Up to 20 months
Secondary Objective Response Rate (ORR) ORR is defined as the number of patients who will experience a complete or partial response divided by the number of patients randomized with at least one target lesion at baseline. Each patient will be assigned the best response ever recorded during the trial a CT-scan will be performed every 4 months. Up to 20 months from last patients randomized
Secondary Quality of Life: Menopause Quality of Life (MENQoL) questionnaire The effect of study treatment will be assessed based on the MENQOL intervention questionnaire based on 29 items divided in four domains (vasomotor, physical, psychosocial and sexual), each scored from 1 to 8 (1 means no symptom, 2 presence of the symptoms but not bothersome, 3-8 an increasing grade of discomfort). Mean changes from the baseline domain scores between treatment arms will be evaluated. Up to 20 months
Secondary Compliance - Number of administered cycles Number of administered cycles Up to 20 months
Secondary Compliance - Reasons for discontinuation and treatment modification Number of patients for each reasons Up to 20 months
Secondary Compliance - Dose intensity Number of tablets taken (i.e., number of tablets given-number of tablets returned)/number of tablets that should have been taken during the treatment period. Up to 20 months
Secondary Safety (Adverse Events) Maximum toxicity grade experienced by each patient for each toxicity, proportion of patients experiencing grade 3-4 toxicity for each toxicity, type, frequency and nature of serious adverse events (SAEs).
Proportion of patients with at least one SAE.
Proportion of patients with at least one serious adverse drug reaction (SADR).
Up to 20 months
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