Clinical trial NCT04460807: Exemestane in Hormone Receptor Positive High Grade Ovarian Cancer
Official title: EXemestane in Progesterone and/or Estrogen Receptor Positive Epithelial Ovarian Cancer: A Randomized Phase III Trial, EXPERT
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Ovarian Cancer
Keywords: exemestane
aromatase inhibitors
clinical trial, phase 3
receptors, estrogen
receptors, progesterone
Lead sponsor: Ente Ospedaliero Ospedali Galliera
Sponsor class: OTHER
Collaborators: name: Istituto Di Ricerche Farmacologiche Mario Negri
name: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
name: Federation of Italian Cooperative Oncology Groups
First posted: 2020-07-08
Enrollment: 23
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: Up to 20 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Up to 20 months
measure: Objective Response Rate (ORR)
timeFrame: a CT-scan will be performed every 4 months. Up to 20 months from last patients randomized
measure: Quality of Life: Menopause Quality of Life (MENQoL) questionnaire
timeFrame: Up to 20 months
measure: Compliance - Number of administered cycles
timeFrame: Up to 20 months
measure: Compliance - Reasons for discontinuation and treatment modification
timeFrame: Up to 20 months
measure: Compliance - Dose intensity
timeFrame: Up to 20 months
measure: Safety (Adverse Events)
timeFrame: Up to 20 months
Other outcomes:
measure: Circulating and tissue biomarkers
timeFrame: Up to 20 months
Locations:
city: Alessandria
country: Italy
facility: AO SS Antonio e Biagio e Cesare Arrigo
state: AL
city: Bari
country: Italy
facility: Ospedale Oncologico IRCCS Bari
state: BA
city: Biella
country: Italy
facility: Ospedale degli Infermi
state: BI
city: Feltre
country: Italy
facility: AULSS 1 Dolomiti - Ospedale "Santa Maria del Prato"
state: BL
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico S.Orsola-Malpighi
state: BO
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia
state: BS
city: Brescia
country: Italy
facility: Fondazione Poliambulanza
state: BS
city: Manerbio
country: Italy
facility: Ospedale di Manerbio
state: BS
city: Cagliari
country: Italy
facility: AOU Cagliari, Policlinico Universitario
state: CA
city: Chieti
country: Italy
facility: Ospedale Policlinico "SS. Annunziata"
state: CH
city: Alba
country: Italy
facility: Azienda Sanitaria Locale CN2
state: CN
city: Cuneo
country: Italy
facility: Azienda Ospedaliera S.Croce e Carle
state: CN
city: Mondovì
country: Italy
facility: Ospedale di Mondovì CN1
state: CN
city: Como
country: Italy
facility: Ospedale Sant Anna di Como
state: CO
city: Catania
country: Italy
facility: ARNAS Garibaldi
state: CT
city: Catania
country: Italy
facility: Azienda Ospedaliera per l'emergenza Cannizzaro
state: CT
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
state: FC
city: San Giovanni Rotondo
country: Italy
facility: Ospedale Casa Sollievo della Sofferenza
state: FG
city: Genova
country: Italy
facility: ASL 3 Ospedale Villa Scassi
state: GE
city: Genova
country: Italy
facility: IRCCS AOU San Martino - IST
state: GE
city: Lecco
country: Italy
facility: ASST Lecco - Ospedale "A. Manzoni"
state: LC
city: Lecce
country: Italy
facility: Ospedale "Vito Fazzi"
state: LE
city: Monza
country: Italy
facility: UOS Oncologia Ginecologica, Ospedale S. Gerardo
state: MB
city: Macerata
country: Italy
facility: Presidio Ospedaliero Unico Av3
state: MC
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia (IEO)
state: MI
city: Modena
country: Italy
facility: AOU Policlinico di Modena
state: MO
city: Palermo
country: Italy
facility: A.R.N.A.S. Ospedali Civico Di Cristina Benfratelli
state: PA
city: Piacenza
country: Italy
facility: Ospedale "Guglielmo da Saliceto"
state: PC
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
state: PI
city: Aviano
country: Italy
facility: CRO Centro di Riferimento Oncologico
state: PN
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
state: PV
city: Potenza
country: Italy
facility: Azienda Ospedaliera Regionale San Carlo
state: PZ
city: Faenza
country: Italy
facility: Ospedale "degli Infermi"
state: RA
city: Lugo
country: Italy
facility: Ospedale "Umberto I"
state: RA
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
state: RA
city: Reggio Emilia
country: Italy
facility: Azienda Ospedaliera Arcispedale Santa Maria Nuova
state: RE
city: Roma
country: Italy
facility: Policlinico Umberto I, Università di Roma "La Sapienza"
state: RM
city: Roma
country: Italy
facility: Policlinico Universitario Fondazione Agostino Gemelli
state: RM
city: Sondrio
country: Italy
facility: ASST Valtellina e Alto Lario
state: SO
city: Sassari
country: Italy
facility: Azienda Ospedaliero Universitaria di Sassari
state: SS
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia - IRCCS
state: TO
city: Torino
country: Italy
facility: AO Ordine Mauriziano
state: TO
city: Torino
country: Italy
facility: Azienda Ospedaliero-Universitaria Città della Salute e della Scienza - Ospedale Ostetrico Ginecologico Sant'Anna
state: TO
city: Vercelli
country: Italy
facility: Presidio Ospedaliero S. Andrea
state: VC
city: Genova
country: Italy
facility: Medical Oncology Division, Ente Ospedaliero Ospedali Galliera
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori - IRCCS "Fondazione G.Pascale"
city: Novara
country: Italy
facility: Azienda Ospedaliero-Universitaria Maggiore della Carità
Study officials:
affiliation: E.O. Ospedali Galliera Genova
name: Andrea DeCensi
role: PRINCIPAL_INVESTIGATOR
References: