Clinical Trials Register

Summary
EudraCT Number:	2018-002514-12
Sponsor's Protocol Code Number:	FACILE
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-20
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-002514-12

A.3

Full title of the trial

Phase II, multicenter, single arm trial to assess the feasibility of first line ribociclib in combination with a non steroidal aromatase inhibitor in elderly patients with hormone receptor positive/HER2 negative advanced breast cancer

FACILE: FeAsibility of first-line riboCIclib in oLdEr patients with advanced breast cancer

Studio di fase II, multicentrico, a braccio singolo, per valutare la fattibilità della combinazione di ribociclib e un inibitore dell’aromatasi non steroideo, in prima linea in anziani affetti da carcinoma mammario avanzato con recettori ormonali positivi/HER2 negativo

A.3.1

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

Combined treatment (hormone and biological therapy) for patients with advanced breast cancer with hormone (HR) positive and HER2 negative receptors

Trattamento combinato (terapia ormonale + biologica) per i pazienti con carcinoma mammario avanzato con recettori ormonali (HR) positivi ed HER2 negativo

A.3.2

Name or abbreviated title of the trial where available

FACILE

A.4.1

Sponsor's protocol code number

FACILE

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	FONDAZIONE SANDRO PITIGLIANI PER LA LOTTA CONTRO I TUMORI - ONLUS
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	Novartis Farma 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	Azienda USL Toscana Centro, Nuovo Ospedale di Prato
B.5.2	Functional name of contact point	SOC Oncologia Medica
B.5.3	Address:
B.5.3.1	Street Address	via Suor Niccolina 20
B.5.3.2	Town/ city	Prato
B.5.3.3	Post code	59100
B.5.3.4	Country	Italy
B.5.4	Telephone number	0574802531
B.5.5	Fax number	0574802903
B.5.6	E-mail	laura.biganzoli@uslcentro.toscana.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	Kisqali
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharma LTD
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Kisqali
D.3.4	Pharmaceutical form	Film-coated 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	Ribociclib
D.3.9.2	Current sponsor code	Non applicabile
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	200
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

HR+, HER2 negative advanced breast cancer

carcinoma mammario avanzato HR positivo HER2 negativo

E.1.1.1

Medical condition in easily understood language

advanced breast cancer

cancro della mammella metastatico

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10072737
E.1.2	Term	Advanced breast cancer
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 assess the feasibility of first-line treatment with ribociclib plus NSAI in a cohort of older patients with advanced breast cancer.

• Valutare la fattibilità di un trattamento di prima linea con ribociclib e NSAI in una coorte di pazienti anziani con tumore mammario avanzato.

E.2.2

Secondary objectives of the trial

• Treatment adherence
• Safety and tolerability
• Patient reported outcomes (PROs)
• Overall response rate (ORR)
• Progression free survival (PFS)

• Aderenza al trattamento
• Sicurezza e tollerabilità
• Risultati riportati dai pazienti (patient reported outcomes - PROs)
• Tasso di risposta globale (overall response rate – ORR)
• Progressione libera da malattia (progression free survival – PFS)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients male or female, aged 70 years-old or older at the time of informed consent.
2. Patients with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
3. Measurable or not measurable but evaluable disease according to RECIST criteria 1.1
4. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
5. Patient has a HER2 negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.

1. Pazienti di sesso maschile o femminile, di età pari o superiore a 70 anni al momento della firma del consenso informato.
2. Pazienti con carcinoma mammario avanzato (recidivato localmente o metastatico) non suscettibili di terapia curativa.
3. Malattia misurabile o non misurabile ma valutabile in base ai criteri RECIST 1.1.
4. Diagnosi istologicamente e/o citologicamente confermata di carcinoma mammario con positività del recettore estrogenico e/o progestinico da parte del laboratorio locale.
5. Carcinoma mammario HER2 negativo definito mediante test di ibridazione in situ negativo o uno stato immunoistochimico (IHC) di 0, 1+ o 2+. In caso di valore IHC è 2+, è richiesto un test di ibridazione in situ negativo (FISH, CISH o SISH) presso il laboratorio locale.

E.4

Principal exclusion criteria

Patients eligible for this study must not meet any of the following criteria:
1. Patient has received prior treatment with chemotherapy or hormonal therapy (except for neoadjuvant/ adjuvant chemotherapy), or any CDK4/6 inhibitor.
NOTE:
- Patients who received (neo) adjuvant therapy for breast cancer are eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole the disease-free interval must be greater than 12 months from the completion of treatment until study entry.
- Patients who received = 28 days of letrozole or anastrozole for advanced disease prior to inclusion in this trial are eligible.
2. Patient has a known hypersensitivity to any of the excipients of ribociclib or NSAI
3. Patient in concurrently using other anti-cancer therapy.
4. Patient who has not had resolution of all acute toxic effects of prior anti-cancer therapy to NCI CTCAE version 5.0 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 radiation 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 investigator’s discretion). Patient from whom = 25% of the bone marrow has been previously irradiated are also excluded
6. Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.

1. Pazienti che hanno ricevuto precedenti trattamenti con chemioterapia o terapia endocrina (eccetto nel setting neoadiuvante o adiuvante) o qualunque inibitore di CDK 4/6.
NOTA:
- I pazienti che hanno ricevuto terapie (neo)adiuvanti per tumore mammario sono eleggibili. Se la precedente terapia (neo)adiuvante comprendeva letrozolo o anastrozolo, l’intervallo libero da malattia (DFS) deve essere maggiore di 12 mesi dalla conclusione del trattamento sino all’ingresso in studio.
- I pazienti che hanno ricevuto = 28 giorni di letrozolo o anastrozolo per precedente malattia avanzata prima dell’inclusione in questo studio sono eleggibili.
2. Pazienti che hanno una nota ipersensibilità a qualunque eccipiente del ribociclib o del letrozolo o dell’anastrozolo.
3. Pazienti sottoposti ad altre terapie anti-tumorali.
4. Pazienti che non hanno avuto risoluzione di tutti gli effetti tossici acuti di precedenti terapie anti-tumorali sino a un grado = 1 secondo CTCAE versione 5.0 (eccetto alopecia o altre tossicità non considerate un rischio per la sicurezza del paziente a discrezione dell’investigatore).
5. Pazienti che hanno ricevuto radioterapia a campo esteso = 4 settimane o radiazioni circoscritte limitate per palliazione = 2 settimane prima dell'inizio del trattamento e che non hanno recuperato al grado = 1 dagli effetti indesiderati correlati a tale terapia (con l'eccezione di alopecia o altre tossicità non considerate un rischio per la sicurezza del paziente a discrezione dello sperimentatore). Sono esclusi anche i pazienti dei quali è stato irradiato = 25% del midollo osseo.
6. Pazienti con una neoplasia concomitante o precedente sino a 3 anni prima dell'inizio dello studio, ad eccezione di carcinoma basocellulare o squamocellulare adeguatamente trattato o tumore cutaneo non melanomatoso o neoplasia della cervice uterina resecato in modo curativo.

E.5 End points

E.5.1

Primary end point(s)

The treatment feasibility will be evaluated as the proportion of patients not having experienced disease progression (PD), still on treatment with ribociclib plus NSAI 6 months after the first drug administration.

La fattibilità del trattamento sarà valutata come la proporzione di pazienti, che non hanno avuto progressione di malattia (PD), ancora in trattamento con ribociclib e letrozolo o anastrozolo 6 mesi dopo la loro prima somministrazione

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months after the first drug administration

6 mesi dalla prima somministrazione

E.5.2

Secondary end point(s)

Treatment adherence

Aderenza al trattamento

E.5.2.1

Timepoint(s) of evaluation of this end point

6 months after the first drug administration

a 6 mesi dalla prima somministrazione

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

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)

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

194

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

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

194

F.4.2

For a multinational trial

F.4.2.1

In the EEA

194

F.4.2.2

In the whole clinical trial

194

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)

clinical practice

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

2019-02-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-11-12

P. End of Trial
P.	End of Trial Status	Ongoing

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