Exemestane in Hormone Receptor Positive High Grade Ovarian Cancer

Ovarian Cancer Clinical Trial

— EXPERT  

Official title:

EXemestane in Progesterone and/or Estrogen Receptor Positive Epithelial Ovarian Cancer: A Randomized Phase III Trial, EXPERT

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04460807
• Other study ID #: 56UCS2017
• Secondary ID: 2018-000693-30
• Status: Terminated
• Phase: Phase 3
• 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
• 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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

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