Exemestane in Hormone Receptor Positive High Grade Ovarian Cancer

NCT ID: NCT04460807

Last Updated: 2024-02-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-13
• Study Completion Date: 2023-04-27

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.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Exemestane

Standard chemotherapy: paclitaxel 175 mg/m2 + carboplatin AUC 5, on day 1 every 21 days ± bevacizumab 15mg/kg, on day 1 every 21 days. Chemotherapy will be administered for 6 cycles; Bevacizumab will be administered as up to a maximum of 22 cycles. Patients unfit for standard treatment can receive a weekly schedule of treatment or monotherapy with carboplatin alone. Neoadjuvant chemotherapy is allowed in patients unfit for primary elective surgery.

+

Exemestane: single oral tablet of 25 mg/day until disease progression, unacceptable toxicity or physician/patient decision to withdraw, whichever comes first.

Group Type: EXPERIMENTAL

Exemestane

Intervention Type: DRUG

Exemestane in addition to standard therapy, in Experimental arm.

Placebo

Standard chemotherapy : paclitaxel 175 mg/m2 + carboplatin AUC 5, on day 1 every 21 days ± bevacizumab 15mg/kg, on day 1 every 21 days. Chemotherapy will be administered for 6 cycles; Bevacizumab will be administered as up to a maximum of 22 cycles. Patients unfit for standard treatment can receive a weekly schedule of treatment or monotherapy with carboplatin alone. Neoadjuvant chemotherapy is allowed in patients unfit for primary elective surgery.

+

Placebo: single oral tablet until disease progression, unacceptable toxicity or physician/patient decision to withdraw, whichever comes first.

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: OTHER

Placebo in addition to standard therapy, in Control arm.

Interventions

Exemestane

Exemestane in addition to standard therapy, in Experimental arm.

Intervention Type: DRUG

Placebo oral tablet

Placebo in addition to standard therapy, in Control arm.

Intervention Type: OTHER

Other Intervention Names

Mestane

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Istituto Di Ricerche Farmacologiche Mario Negri

OTHER

Sponsor Role: collaborator

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: collaborator

Federation of Italian Cooperative Oncology Groups

OTHER

Sponsor Role: collaborator

Ente Ospedaliero Ospedali Galliera

OTHER

Sponsor Role: lead

Responsible Party

Andrea DeCensi

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrea DeCensi

Role: PRINCIPAL_INVESTIGATOR

E.O. Ospedali Galliera Genova

Locations

AO SS Antonio e Biagio e Cesare Arrigo

Alessandria, AL, Italy

Ospedale Oncologico IRCCS Bari

Bari, BA, Italy

Ospedale degli Infermi

Biella, BI, Italy

AULSS 1 Dolomiti - Ospedale "Santa Maria del Prato"

Feltre, BL, 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

Ospedale di Manerbio

Manerbio, BS, Italy

AOU Cagliari, Policlinico Universitario

Cagliari, CA, Italy

Ospedale Policlinico "SS. Annunziata"

Chieti, CH, Italy

Azienda Sanitaria Locale CN2

Alba, CN, Italy

Azienda Ospedaliera S.Croce e Carle

Cuneo, CN, Italy

Ospedale di Mondovì CN1

Mondovì, CN, Italy

Ospedale Sant Anna di Como

Como, CO, Italy

ARNAS Garibaldi

Catania, CT, Italy

Azienda Ospedaliera per l'emergenza Cannizzaro

Catania, CT, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS

Meldola, FC, Italy

Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, FG, Italy

ASL 3 Ospedale Villa Scassi

Genova, GE, Italy

IRCCS AOU San Martino - IST

Genova, GE, Italy

ASST Lecco - Ospedale "A. Manzoni"

Lecco, LC, Italy

Ospedale "Vito Fazzi"

Lecce, LE, Italy

UOS Oncologia Ginecologica, Ospedale S. Gerardo

Monza, MB, Italy

Presidio Ospedaliero Unico Av3

Macerata, MC, Italy

Istituto Europeo di Oncologia (IEO)

Milan, MI, Italy

AOU Policlinico di Modena

Modena, MO, Italy

A.R.N.A.S. Ospedali Civico Di Cristina Benfratelli

Palermo, PA, Italy

Ospedale "Guglielmo da Saliceto"

Piacenza, PC, Italy

Azienda Ospedaliero-Universitaria Pisana

Pisa, PI, Italy

CRO Centro di Riferimento Oncologico

Aviano, PN, Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, PV, Italy

Azienda Ospedaliera Regionale San Carlo

Potenza, PZ, Italy

Ospedale "degli Infermi"

Faenza, RA, Italy

Ospedale "Umberto I"

Lugo, RA, 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

ASST Valtellina e Alto Lario

Sondrio, SO, Italy

Azienda Ospedaliero Universitaria di Sassari

Sassari, SS, Italy

Fondazione del Piemonte per l'Oncologia - IRCCS

Candiolo, TO, 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, Italy

Medical Oncology Division, Ente Ospedaliero Ospedali Galliera

Genova, , Italy

Istituto Nazionale Tumori - IRCCS "Fondazione G.Pascale"

Napoli, , Italy

Azienda Ospedaliero-Universitaria Maggiore della Carità

Novara, , Italy

Countries

Italy

Other Identifiers

2018-000693-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

56UCS2017

Identifier Type: -

Identifier Source: org_study_id