Clinical Trials Register

Summary
EudraCT Number:	2014-005696-93
Sponsor's Protocol Code Number:	ACT14205
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:	2021-05-27
Trial results	View 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

2014-005696-93

A.3

Full title of the trial

Phase II, Open Label, Single Arm Study Assessing the Clinical Benefit of SAR125844, Administered as Single Agent by Weekly Intravenous (IV) Infusion, for the Treatment of Patients with Advanced Pretreated Non-Small Cell Lung Cancer (NSCLC) Harboring MET Gene Amplification

Studio di fase II, in aperto, su braccio singolo per valutare il beneficio clinico di SAR125844, somministrato come agente singolo in infusione endovenosa settimanale, per il trattamento di pazienti con tumore polmonare non a piccole
cellule (NSCLC) in stadio avanzato, pretrattato e con amplificazione del gene MET

A.3.1

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

Phase II Study Assessing Efficacy and Safety of SAR125844 in NSCLC Patients with MET Amplification

Studio di fase II per valutare l'efficacia e la sicurezza di SAR125844 in pazienti NSCLC con amplificazione del gene MET

A.3.2

Name or abbreviated title of the trial where available

ACT14205

A.4.1

Sponsor's protocol code number

ACT14205

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	SANOFI-AVENTIS RECHERCHE E DEVELOPPEMENT
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sanofi S.p.A.
B.5.2	Functional name of contact point	CONTACT POINT
B.5.3	Address:
B.5.3.1	Street Address	VIALE BODIO, 37/B
B.5.3.2	Town/ city	MILANO
B.5.3.3	Post code	20158
B.5.3.4	Country	Italy
B.5.4	Telephone number	800226343
B.5.5	Fax number	00390239394168
B.5.6	E-mail	informazioni.medicoscientifiche@sanofi.com

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	No
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	SAR125844
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1116743-46-4
D.3.9.2	Current sponsor code	SAR125844
D.3.9.4	EV Substance Code	SUB88508
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
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

Neoplasm malignant

Tumore maligno

E.1.1.1

Medical condition in easily understood language

Neoplasm malignant

Tumore maligno

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	PT
E.1.2	Classification code	10028997
E.1.2	Term	Neoplasm malignant
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 determine objective response rate (ORR).

Determinazione del tasso di risposta obiettiva (ORR).

E.2.2

Secondary objectives of the trial

- To assess duration of response (DR), progression free survival (PFS) and overall survival (OS).
- To evaluate global safety profile.
- To determine pharmacokinetic profile.
- To assess clinical utility of fluorescence in situ hybridization (FISH) assay in selection of patients with mesenchymal-epithelial hybridization (MET) gene amplifcation.
- To assess lung cancer symptoms, health-related quality of life and treatment satisfaction.

- Valutazione della durata della risposta (DR), della sopravvivenza libera da progressione (PFS) e della sopravvivenza globale (OS)
- Valutazione del profilo di sicurezza globale
- Determinazione del profilo farmacocinetico
- Valutazione dell'utilit¿ clinica del test di ibridazione fluorescente in situ (FISH) per la selezione dei pazienti con amplificazione del gene MET
- Valutazione dei sintomi specifici del tumore del polmone, della qualit¿ della vita correlata alla salute e della soddisfazione rispetto al trattamento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Metastatic non-small-cell lung cancer patients with progressive disease during or after first or second line therapy harboring MET gene amplification and with measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

NSCLC metastatico in pazienti con progressione di malattia durante o dopo la prima o seconda linea di terapia con amplificazione del gene MET e malattia misurabile in base a criteri RECIST 1.1

E.4

Principal exclusion criteria

- Eastern Cooperative Oncology Group (ECOG) performance status >2.
- More than 2 episodes of disease progression under anticancer therapy.
- Wash out period of less than 3 weeks from prior treatment with chemotherapy, radiotherapy or, surgery or any investigational treatment.
- Adequate hematologic, hepatic, renal, coagulation, and metabolic functions.
- No resolution of any specific toxicities (excluding alopecia) related to any prior anti-cancer therapy to grade =1 according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.03.
- Pregnant or breast-feeding women.
- Patient with reproductive potential without method of contraception.
- Symptomatic brain metastasis.
- Any clinically significant medical condition other than cancer which could interfere with the safe delivery of study treatment or risk of toxicity.
- Known hypersensitivity or any adverse event related to the study drug excipient (Captisol®).
- Prior treatment with any MET Tyrosine Kinase Inhibitors (TKIs) or anti-MET antibodies (excluding onartuzumab).
- Patients treated with potent CYP3A inhibitor unless it can be discontinued.
- Patients treated with potent and moderate CYP3A inducers unless it can be discontinued.
- Mean QTc interval prolongation >470 msec.

- Pazienti di età inferiore a 18 anni
- Eastern Cooperative Oncology Group (ECOG) performance status > 2
- Più di 2 episodi di progressione di malattia in precedente terapia antitumorale
- Periodo di wash out inferiore a 3 settimane dal precedente trattamento chemioterapico, radioterapia, chirurgia o qualsiasi altro trattamento sperimentale
- Adeguata funzionalità ematologica, epatica, renale, coagulazione e metabolica
- Mancata risoluzione di qualsiasi tossicità specifica (esclusa alopecia) correlata a qualunque precedente terapia antitumorale a un grado = 1 in accordo ai criteri NCI-CTCAE v.4.03
- Donne in gravidanza o in fase di allattamento
- Pazienti in età fertile senza un metodo contraccettivo
- Metastasi cerebrali sintomatiche
- Qualsiasi altra grave condizione medica oltre al tumore che possa interferire con la capacità di partecipare allo studio o con l'interpretazione dei risultati.
- Ipersensibilità nota o qualsiasi evento avverso correlato all'eccipiente del farmaco dello studio (Captisol®).
- Precedente trattamento con inibitori della tirosin-chinasi MET (TKIs) o anticorpi anti-MET (escluso onartuzumab).
- Pazienti trattati con potenti inibitori del CYP3A eccetto se interrotti
- Pazienti trattati con potenti e moderati induttori del CYP3A eccetto se possono essere Interrotti
- Intervallo QTc medio > 470 msec

E.5 End points

E.5.1

Primary end point(s)

Determination of the objective response rate of SAR125844 as per RECIST 1.1

Determinazione della risposta obiettiva di SAR125844 in accordo ai criteri RECIST 1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

Every 6 weeks up to disease progression

Ogni 6 settimane fino a progressione della malattia

E.5.2

Secondary end point(s)

Progression-free survival rate; Overall survival rate; Proportion of patients with adverse events; Assessment of pharmacokinetic parameters: maximum plasma concentration (Cmax); Assessment of pharmacokinetic parameters: area under curve (AUC); Assessment of pharmacokinetic parameters: half-life (t1/2); Assessment of pharmacokinetic parameters: total clearance (CL); Assessment of lung cancer symptoms by Core Quality of Life questionnaire (QLQ-C30) +LC13; Assessment of health-related quality of life by QLQ-C30/LC13; Assessment of treatment satisfaction by Cancer Therapy Satisfaction Questionnaire

Sopravvivenza libera da progressione; Sopravvivenza globale; Proporzione di pazienti con eventi avversi; Valutazione dei parametri farmacocinetici: concentrazione massima di plasma (Cmax); Valutazione dei parametri farmacocinetici: area sotto la curva (AUC); Valutazione dei parametri farmacocinetici: met¿ vita (t1/2); Valutazione dei parametri farmacocinetici: clearance totale (CL); Valutazione dei sintomi di tumore polmonare attraverso questionario sulla qualit¿ della vita (QLQ-C30) +LC13; Valutazione della salute connessa alla qualit¿ della vita attraverso QLQ-C30/ LC13; Valutazione della soddisfazione del trattamento mediante il Cancer Therapy Satisfaction Questionnaire

E.5.2.1

Timepoint(s) of evaluation of this end point

Up to 34 months; Up to 34 months; Up to 40 months; Up to 3 days; Up to 3 days; Up to 3 days; Up to 3 days; Every 3 weeks up to 34 months; Every 3 weeks up to 34 months; Every 6 weeks up to 34 months

Fino a 34 mesi; Fino a 34 mesi; Fino a 40 mesi; Fino a 3 giorni; Fino a 3 giorni; Fino a 3 giorni; Fino a 3 giorni; Ogni 3 settimane fino a 34 mesi; Ogni 3 settimane fino a 34 mesi; Ogni 6 settimane fino a 34 mesi

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Lung Cancer symptoms, health-related quality of life, and treatment satisfaction

Sintomi cancro ai polmoni, qualit¿ della vita connessa alla salute, e soddisfazione del trattamento

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

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

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:

112

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

156

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

161

F.4.2.2

In the whole clinical trial

168

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)

none

nessuno

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

2015-07-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-04-01

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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