Clinical Trials Register

Summary
EudraCT Number:	2013-000490-79
Sponsor's Protocol Code Number:	AB12010
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-06-16
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

France - ANSM

A.2

EudraCT number

2013-000490-79

A.3

Full title of the trial

A prospective, multicenter, randomized, double blind, placebo-controlled, 2-parallel groups, phase 3 study to compare the efficacy and safety of masitinib in combination with FOLFIRI (irinotecan, 5-fluorouracil and folinic acid) to placebo in combination with FOLFIRI in second line treatment of patients with metastatic colorectal cancer

Etude de phase 3, prospective, multicentrique, randomisée, en double aveugle, contrôlée, avec 2 groupes parallèles, visant à comparer l’efficacité et la tolérance de masitinib en association avec FOLFIRI (irinotecan, 5-fluorouracil et acide folinique) versus placebo en association avec FOLFIRI, chez des patients atteint d’un cancer colorectal métastatique en 2ème ligne de traitement

A.3.1

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

Study to evaluate 2 types of treatment (masitinib + FOLFIRI or placebo + FOLFIRI) in the treatment of patients with metastatic colorectal cancer that have received 1 previous therapy

Etude visant à comparer 2 types de traitement (masitinib + FOLFIRI ou placebo + FOLFIRI) chez des patients atteints d'un cancer colorectal métastatique et qui ont déjà reçu une première ligne de traitement

A.4.1

Sponsor's protocol code number

AB12010

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	AB Science
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	AB Science
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	AB Science
B.5.2	Functional name of contact point	Olivier EYDOUX
B.5.3	Address:
B.5.3.1	Street Address	3 avenue George V
B.5.3.2	Town/ city	PARIS
B.5.3.3	Post code	75008
B.5.3.4	Country	France
B.5.4	Telephone number	+331 47 20 32 00
B.5.5	Fax number	+331 47 20 24 11
B.5.6	E-mail	olivier.eydoux@ab-science.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.2.1.2	Country which granted the Marketing Authorisation	France
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	masitinib 100mg
D.3.2	Product code	AB1010
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.3.11 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)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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.IMP: 2
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.2.1.2	Country which granted the Marketing Authorisation	France
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	masitinib 200mg
D.3.2	Product code	AB1010
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.3.11 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)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Metastatic colorectal cancer after 1 previous line of treatment

Cancer colorectal métastatique après une première ligne de traitement

E.1.1.1

Medical condition in easily understood language

Metastatic colorectal cancer

Cancer colorectal métastatique

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	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10052362
E.1.2	Term	Metastatic colorectal 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

Overall survival (OS)

E.2.2

Secondary objectives of the trial

Tumor assessment
- Overall Progression Free Survival (PFS)
- PFS rate every 8 weeks
- Overall Time To Progression (TTP)
- TTP rate every 8 weeks
- Best response rate, Objective response rate (CR + PR) and Disease control rate (CR + PR + SD) every 8 weeks
• Quality of life assessment at week every 8 weeks
- ECOG Performance Status
- Quality of Life according to the EORTC QLQ-C30
- Analgesic intake
- Pain improvement (VAS)
• Pharmacogenomic assessment (Relationship between genomic data and overall survival)
• Safety profile using the NCI CTCAE v4.02 classification

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient with non-resectable metastatic colorectal cancer with histological or cytological documentation of adenocarcinoma of the colon or rectum
2. Metastatic disease not amenable to surgical resection with curative intent
3. Patient in second line treatment after progression according to RECIST criteria following administration of a standard chemotherapy regimen for treatment of metastatic disease
4. Patient with measurable lesions according to RECIST criteria (version 1.1) with spiral CT scan and defined as 10 mm in longest diameter and 2X the slice thickness for extra nodal lesions and/or >15 mm in short axis diameter for nodal lesions
5. Patient with ECOG ≤ 2
6. Patient with adequate organ function
• Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
• Haemoglobin ≥ 10 g/dl
• Platelets (PLT) ≥ 75 x 109/L
• AST/ALT ≤ 3 x ULN (≤ 5 x ULN in case of liver metastases)
• GammaGT ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastases)
• Bilirubin ≤ 1.5 x ULN
• Normal Creatinine or if abnormal creatinine, creatinine clearance ≥ 50 mL/min (Cockcroft and Gault formula)
• Albumin > 1 x LLN
• Proteinuria < 30 mg/dL (1+) on the dipstick. If proteinuria is ≥ 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours
7. Patient with life expectancy > 3 months
8. Female or male patient ≥ 18
9. Patient weight >40 kg and BMI > 18
10. Man and woman of childbearing potential, who agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake
11. Female patient of childbearing potential must have a negative pregnancy test at screening and baseline
12. Patient able and willing to comply with study procedures as per protocol
13. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures are performed. If the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable, the designated legal guardian must sign the informed consent.
14. Patient able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity during the first 2 months of treatment.
15. Patient affiliated to a social security system

E.4

Principal exclusion criteria

1. Patient intolerant to one of these treatments: irinotecan, 5-fluorouracil (5-FU), folinic acid
2. More than 1 prior chemotherapy regimens for metastatic colorectal cancer.
3. Pregnant, intent to be pregnant, or nursing female patient
4. Patient with any chronic inflammatory bowel disease
5. Patient treated for a cancer other than colorectal cancer within five years before enrollment, with the exception of basal cell carcinoma or cervical cancer in situ
6. Patient with an hepatic involvement > 50%
7. Patient with active central nervous system (CNS) metastasis or history of CNS metastases
8. Patient with an active infection (Human immunodeficiency virus infection and/or hepatitis B or C infection …)
9. Patient presenting with cardiac disorders defined by at least one of the following conditions:
• Patient with recent cardiac history (within 6 months) of:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
• Patient with cardiac failure class III or IV of the NYHA classification
• Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
• Syncope without known aetiology within 3 months
• Uncontrolled severe hypertension, according to the judgement of the investigator, or symptomatic hypertension
10. Patient with a history of poor compliance or of drug/alcohol abuse, or excessive alcohol beverage consumption, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
WASH OUT
11. Any previous treatment with an investigational agent or chemotherapy or biological agent will require a wash-out period of four weeks prior to baseline.
________________________________________

E.5 End points

E.5.1

Primary end point(s)

• Overall Survival (OS) is defined as the time from the randomization to the date of documented death

E.5.1.1

Timepoint(s) of evaluation of this end point

Date of documented death

E.5.2

Secondary end point(s)

• Survival rate is defined as the rate of patients alive at each time point
• Overall Progression Free Survival (PFS) is defined as the delay between the date of randomization to the date of documented progression or any cause of death during the study. Progression will be assessed by CT scan according to RECIST criteria version 1.1 as defined in table 5.
• PFS rate is defined as the rate of patients without progression or death at each time point
• Overall Time To Progression (TTP) is defined as the time from the date of randomization to the date of documented progression defined according to RECIST criteria version 1.1
• TTP rate is defined as the rate of patients without documented progression at each time point
• Best Response is defined as the best response (CR or PR or SD or PD) defined according to to RECIST criteria version 1.1 recorded from the start of the treatment until end of study.
• Best Response rate is defined as the number of patients achieving the Best Response divided by the total number of patients in the population of analysis.
• Objective response rate (CR + PR) is defined as the number of patients with documented partial response or complete response defined according to RECIST, divided by the number of randomized patients
• Disease control rate (CR + PR + SD) is defined as the number of patients with documented partial response, complete response or stable disease defined according to RECIST criteria version 1.1, divided by the number of patients randomized at each time point.

E.5.2.1

Timepoint(s) of evaluation of this end point

Every 8 weeks

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

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Information not present in EudraCT

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Information not present in EudraCT

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

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

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

Argentina

Canada

China

Hong Kong

India

Korea, Republic of

Malaysia

Mexico

Morocco

Peru

Philippines

Russian Federation

South Africa

Tunisia

Ukraine

United States

E.8.7

Trial has a data monitoring committee

Yes

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

patient treated until disease progression limitoing toxicity or consnet withdrawal. Follow-up performed until patient's death

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

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:

350

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

200

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

200

F.4.2

For a multinational trial

F.4.2.1

In the EEA

350

F.4.2.2

In the whole clinical trial

550

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

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

2013-11-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-10-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-07-28

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