Clinical Trials Register

Summary
EudraCT Number:	2019-000510-11
Sponsor's Protocol Code Number:	Hermione-7
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-06-14
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2019-000510-11

A.3

Full title of the trial

A Phase 2, open label, multicenter, single arm trial evaluating the activity and safety of Abemaciclib + Aromatase Inhibitors (AIs) after 1st-line treatment with High-Dose Fulvestrant in Hormone-Receptor-Positive (HR+), Human-Epidermal-Growth-factor-negative (HER2-) advanced breast cancer patients. The HERMIONE-7 trial

Studio di fase 2, in aperto, multicentrico, a braccio singolo per valutare l'attività e la sicurezza degli Inibitori di Aromatasi (AI) in associazione ad Abemaciclib in pazienti affetti da carcinoma mammario avanzato positivo per il recettore ormonale (HR+), HER2 negativo dopo il trattamento di prima linea con Fulvestrant ad alto dosaggio (HD-FUL). Lo studio HERMIONE-7

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Clinical study to evaluate the activity and safety of Aromatase inhibitors administered together with Abemaciclib in patients with advanced breast cancer after treatment with high-dose Fulvestrant.

Studio clinico per valutare l'attività e la sicurezza degli Inibitori di Aromatasi somministrati insieme ad Abemaciclib in pazienti con tumore mammario avanzato dopo il trattamento con Fulvestrant ad alte dosi.

A.3.2

Name or abbreviated title of the trial where available

Hermione-7

A.4.1

Sponsor's protocol code number

Hermione-7

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	UNIVERSITÀ DEGLI STUDI MILANO BICOCCA
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Eli Lilly Italia S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ASST Monza
B.5.2	Functional name of contact point	UOC Centro di Ricerca di Fase 1 - d
B.5.3	Address:
B.5.3.1	Street Address	via Pergolesi, 33
B.5.3.2	Town/ city	Monza
B.5.3.3	Post code	20900
B.5.3.4	Country	Italy
B.5.4	Telephone number	0392339037
B.5.5	Fax number	0392333539
B.5.6	E-mail	dir.centroricerca@asst-monza.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	verzenios
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly Nederland BV
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	abemaciclib
D.3.2	Product code	[abemaciclib]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	abemaciclib
D.3.9.2	Current sponsor code	abemaciclib
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced breast cancer Hormone-Receptor-Positive (HR+), Human-Epidermal-Growth-factor-negative (HER2-)

Carcinoma mammario avanzato positivo al recettore ormonale (HR+), negativo al fattore di crescita epidermico umano (HER2-)

E.1.1.1

Medical condition in easily understood language

Advanced breast cancer

Tumore della mammella in stadio avanzato

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10006283
E.1.2	Term	Breast neoplasm malignant female
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To describe the activity of Abemaciclib with aromatase inhibitors (letrozole or anastrozole) in high dose fulvesartan (HD-FUL) pre-treated metastatic breast cancer patients in terms of clinical benefit rate (CBR).

Descrivere l'attività di abemaciclib più inibitori dell'aromatasi (letrozolo o anastrozolo) in pazienti con carcinoma della mammella avanzato pre-trattati con alte dosi di fulvesartan (HD-FUL) in termini di tasso di beneficio clinico (CBR).

E.2.2

Secondary objectives of the trial

• To evaluate the efficacy in terms of Time To Progression (TTP)
• To evaluate the efficacy in terms of Overall Response Rate (ORR)
• To estimate Duration of Overall Response (DoOR)
• To evaluate duration of Clinical Benefit (DoCB)
• To assess the safety profile of Abemaciclib in association with aromatase inhibitors (letrozole or anastrozole)
• To evaluate the activity of Abemaciclib with aromatase inhibitors according to the duration of previous HD-FUL treatment

Descrivere:
• Tempo di progressione (TTP)
• Tasso di risposta globale (ORR)
• Durata della risposta (DoOR)
• Durata del beneficio clinico (DoCB)
• Sicurezza
• l'attività di abemaciclib più inibitori di aromatasi in accordo alla durata del precedente trattamento con HD-FUL

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Female >= 18 years of age regardless of menopausal status, who have relapsed while on prior first-line therapy with HD-FUL
2. Patients with advanced (loco-regionally recurrent, or metastatic) breast cancer not amenable to curative therapy.
3. Patient has a histological and/or cytological confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
4. WHO performance status of 0–2
5. Measurable disease (according to Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1) or at least one lytic bone lesion
6. The patient is able to swallow oral medications.
7. The patient has adequate organ function
8. Patient has signed ICF (ICF) obtained before any trial-related activities Patients must be able to communicate with the investigator and comply with the requirements of the study procedures

1. Donne di età >= 18 anni indipendentemente dallo stato di menopausa, che hanno recidivato durante la precedente terapia di prima linea con HD-FUL
2. pazienti con carcinoma mammario avanzato (con recidiva locale o metastatico) non suscettibili a terapia curativa.
3. pazienti con una diagnosi istologica e/o citologica confermata da laboratorio locale di carcinoma mammario positivo a recettore estrogeno e/o a recettore progesterone.
4. WHO performance status di 0 – 2
5. Malattia misurabile (secondo i criteri di valutazione della risposta in tumori solidi [RECIST], versione 1,1) o almeno una lesione ossea litica
6. il paziente è in grado di deglutire farmaci orali.
7. il paziente ha una funzione di organo adeguata
8. il paziente ha firmato il consenso informato (ICF) ottenuto prima di qualsiasi attività correlata alla sperimentazione; i pazienti devono essere in grado di comunicare con lo sperimentatore e rispettare i requisiti delle procedure di studio

E.4

Principal exclusion criteria

1. Patient has a known hypersensitivity to any of the excipients of Abemaciclib or letrozole/anastrozole
2. Patient who received any CDK4/6 inhibitor
3. Patient who received > 1 prior systemic hormonal therapy for advanced breast cancer; the only admitted previous therapy as 1st-line treatment is HD FUL. Note: Patients who received >= 28 days of letrozole or anastrozole for advanced disease prior to inclusion in this trial are eligible.
4. Patient who has not had resolution of all acute toxic effects of prior anti-cancer therapy to NCI CTCAE version 4.03 Grade <= 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion)
5. Patient who has received extended-field radiotherapy <= 4 weeks or limited field radiotherapy for palliation <= 2 weeks prior to start of treatment, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia or other toxicities not considered a safety risk for the patient at the investigator’s discretion).
6. Patients from whom >= 25% (Ellis RE 1961) of the bone marrow has been previously irradiated are also excluded.
7. Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of treated, basal or squamous cell carcinoma, non melanomatous skin cancer or curatively resected cervical cancer.
8. Patient with central nervous system (CNS) metastases unless they meet ALL of the following criteria:
a. At least 4 weeks from prior therapy for CNS disease completion (including radiation and/or surgery) to starting the study treatment
b. Clinically stable CNS lesions at the time of study treatment initiation and not receiving steroids and/or enzyme-inducing anti-epileptic medications for the management of brain metastases for at least 2 weeks
9. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection, or preexisting Crohn’s disease or ulcerative colitis, or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)
10. Patient has a known history of HIV infection (testing not mandatory)
11. The patient has serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (such as severe renal impairment, [for example, estimated creatinine clearance <30 mL/min], interstitial lung disease, sever dyspnea at rest or requiring oxygen therapy
12. The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Exception: patients with controlled atrial fibrillation for >30 days prior to randomization are eligible. Any patient with a history of VTE (for example, DVT of the leg or arm and/or PE) will be excluded

1. il paziente ha una nota ipersensibilità ad uno qualsiasi degli eccipienti di Abemaciclib o letrozolo/anastrozolo
2. paziente che ha ricevuto un inibitore di CDK4/6
3. paziente che ha ricevuto più di una precedente terapia ormonale sistemica per carcinoma mammario avanzato; l'unica terapia precedentemente ammessa come trattamento di prima linea è HD-FUL.
4. paziente che non ha avuto la risoluzione di tutti gli effetti tossici acuti della precedente terapia antitumorale ad un grado <= 1 secondo i criteri NCI CTCAE 4.03 (eccetto alopecia o altre tossicità non considerate dallo sperimentatore un rischio per la sicurezza del paziente)
5. paziente che ha ricevuto radioterapia a campo esteso <= 4 settimane o radioterapia circoscritta palliativa <= 2 settimane prima dell'inizio del trattamento e che non ha recuperato almeo a grado 1 dagli effetti indesiderati correlati a tale terapia (ad eccezione dell'alopecia o altre tossicità non considerate dallo sperimentatore un rischio per la sicurezza del paziente).
6. sono esclusi anche i pazienti dai quali è stato precedentemente irradiato >= 25% del midollo osseo (Ellis RE 1961).
7. pazienti con un tumore concomitante o che hanno avuto un tumore entro 3 anni prima di iniziare il farmaco di studio, ad eccezione del carcinoma a cellule basali o squamose trattato, tumore della pelle non melanoma o tumore della cervice resecato.
8. pazienti con metastasi del sistema nervoso centrale (CNS) a meno che non soddisfino tutti i seguenti criteri:
a. almeno 4 settimane dalla precedente terapia per la malattia del CNS (comprese le radiazioni e/o la chirurgia) prima di iniziare il trattamento in studio
b. lesioni del CNS clinicamente stabili al momento dell'inizio del trattamento di studio e che non ricevono terapie steroidee e/o farmaci anti-epilettici che inducano gli enzimi, usati per il trattamento delle metastasi cerebrali, per almeno 2 settimane
9. il paziente ha una compromissione della funzione gastrointestinale (GI) o è affetto da una malattia GI che può alterare significativamente l'assorbimento dei farmaci dello studio (ad esempio, malattie ulcerative incontrollate, nausea, vomito, diarrea incontrollate, sindrome da malassorbimento o resezione dell’intestino tenue, o malattia di Crohn preesistente o colite ulcerosa, o una condizione cronica preesistente risultante in diarrea di grado 2 o superiore)
10. il paziente ha una storia nota di infezione da HIV (test non obbligatorio)
11. il paziente ha gravi condizioni mediche preesistenti che, a giudizio dello sperimentatore, impedirebbero la partecipazione a questo studio (come la compromissione renale severa, [ad esempio, la clearance della creatinina stimata <30 ml/min], malattia polmonare interstiziale, dispnea severa a riposo o che richiede ossigeno)
12. Il paziente ha una storia clinica che include una qualsiasi delle seguenti condizioni: sincope di eziologia cardiovascolare, aritmia ventricolare di origine patologica (compresi, ma non limitati a, tachicardia ventricolare e fibrillazione ventricolare), o arresto cardiaco improvviso. Eccezione: i pazienti con fibrillazione atriale controllata per > 30 giorni prima della randomizzazione sono ammissibili. Qualsiasi paziente con una storia di tromboembolismo venoso (ad esempio, trombosi venosa profonda della gamba o del braccio e/o embolia polmonare) sarà escluso.

E.5 End points

E.5.1

Primary end point(s)

Clinical benefit rate (CBR) is defined as the proportion of patients in Complete Response (CR), Partial Response (PR) or with Stable Disease (SD) >= 24 weeks (as defined by RECIST 1.1 Criteria) evaluated at 6 months from treatment initiation.

Il tasso di beneficio clinico (CBR) è definito come la proporzione di pazienti in risposta completa (CR), risposta parziale (PR) o con malattia stabile (SD)> = 24 settimane (come definito dai criteri di RECIST 1.1) valutati a 6 mesi dall'inizio del trattamento.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months from treatment initiation.

6 mesi dell'inizio del trattamento

E.5.2

Secondary end point(s)

Time to Progression (TTP); Overall response rate (ORR); Duration of Overall Response (DoOR); Duration of Clinical Benefit (DoCB); Safety

Tempo di progressione (TTP); Tasso di risposta globale (ORR); Durata della risposta (DoOR); Durata del beneficio clinico (DoCB); Sicurezza

E.5.2.1

Timepoint(s) of evaluation of this end point

Entire study duration; Entire study duration; Entire study duration; Entire study duration; Entire study duration

Intera durata dello studio; Intera durata dello studio; Intera durata dello studio; Intera durata dello studio; Intera durata dello studio

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

121

F.4.2

For a multinational trial

F.4.2.1

In the EEA

121

F.4.2.2

In the whole clinical trial

121

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will be treated as per local clinical practice

I pazienti verranno trattati come da normale pratica clinica

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-10-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-12

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-12-31

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials