Clinical Trials Register

Summary
EudraCT Number:	2013-002293-41
Sponsor's Protocol Code Number:	AB12005
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Temporarily Halted
Date on which this record was first entered in the EudraCT database:	2014-06-21
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

UK - MHRA

A.2

EudraCT number

2013-002293-41

A.3

Full title of the trial

A prospective, multicenter, double-randomised, double-blind, 2-parallel groups, phase 3 study to compare as first line therapy efficacy and safety of masitinib in combination with gemcitabine, to gemcitabine in combination with placebo, followed as second line treatment by masitinib in combination with Folfiri 3 versus placebo in combination with Folfiri 3 in the treatment of patients with non resectable locally advanced or metastatic pancreatic cancer

A.3.1

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

A specially designed study at many medical sites to compare whether Masitinib in combination with a currently available medicines which are used for first line & second line treatments, namely gemcitabine or with a currently available series of medicinal treatments (called Folfiri 3), is effective and safe for the treatment of certain types of pancreatic cancer which cannot be removed or is spreading in the body.

A.3.2

Name or abbreviated title of the trial where available

AB12005

A.4.1

Sponsor's protocol code number

AB12005

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	Clinical Study Project Manager
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	+ 33 147 20 66 23
B.5.5	Fax number	+ 33 147 20 24 11
B.5.6	E-mail	elena.radu@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.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/09/684
D.3 Description of the IMP
D.3.1	Product name	Masitinib mesylate
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Masitinib mesylate
D.3.9.1	CAS number	790-299-79-5
D.3.9.3	Other descriptive name	MASITINIB MESYLATE
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	119.3 to 238.5
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	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	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

Non-resectable locally advanced or metastatic pancreatic cancer.

E.1.1.1

Medical condition in easily understood language

Tumour in the pancreas that can't be surgically removed or cancer that has spread from where it started in the pancreas to other parts of the body.

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	17.0
E.1.2	Level	PT
E.1.2	Classification code	10033610
E.1.2	Term	Pancreatic carcinoma metastatic
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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare efficacy and safety of masitinib in combination with gemcitabine to placebo in combination with gemcitabine, in treatment of patients with advanced/metastatic pancreatic cancer.

E.2.2

Secondary objectives of the trial

To compare efficacy and safety of masitinib in combination with Folfiri.3 to placebo in combination with Folfiri.3, in the treatment of patients previously treated by masitinib in combination with gemcitabine who were progressive, or non progressive and having discontinued study for any adverse event not defined as a severe adverse event (grade ≥ 3) due to the mechanism of action of masitinib.

During this study, a pharmacogenomic study will be performed in order to confirm or define predictive criteria of overall survival from genomic data.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

During this study, a pharmacogenomic assessment will be conducted of pancreatic tumours from patients in the main study. An analysis of the regions coding for some kinases as c-kit, PDGF-R, FGF-R3, JAK, LYN, FYK, LCK).will be done and results will be correlated to the proteins expression. Two specific blood samples per patient will be regularly performed: at W0, W1, W2 and W12. These samples will be done according to the process described in the ‘Manual for pharmacogenomic study’. The objective of this ancillary study is to evaluate modifications and amplification of genes coding for kinases and other genes that could be predictive of sensitivity and/or resistance to study treatment, and so to confirm or redefine the ‘genetic fingerprint’ discovered as a predictive endpoint in the previous study.

E.3

Principal inclusion criteria

1. Histologically or cytologically confirmed adenocarcinoma of the pancreas
2. Patient with pain related to the disease, as assessed by the investigator and the patient:
- Pain related to the disease as assessed by the investigator is defined as clinical and documented evaluation by the investigator during physical examinations at screening and/or baseline.
- Pain, as assessed by the patient is defined as at least one value out of two values > 5mm on Visual Analogic Scale at screening or baseline. Visual Analogic scale consists in the visual representation of pain amplitude as perceived by the patient. The amplitude is represented by a 100 mm long line having no reference marks. One extremity indicates an absence of pain (0 value) and the other the worst imaginable pain (100 value).
OR
Patient treated with opioid analgesics at a dose ≥ 1 mg/kg/day (morphinic equivalent).
OR
Patients with ‘genetic fingerprint of aggressiveness’:
3. Chemotherapy naïve patient for the advanced/metastatic disease
4. Documented decision justifying non eligibility for surgical resection.
5. Patient with measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according to RECIST 1.1
6. Patient with ECOG ≤ 1
7. Patient with adequate organ functions:
-Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
- Haemoglobin ≥ 10 g/dL
- Platelets (PTL) ≥ 75 x 109/L
- AST/ALT ≤ 5 x ULN
- Gamma GT ≤ 5 x ULN
- Bilirubin ≤ 3 x ULN
- Normal Creatinine or if abnormal creatinine, creatinine clearance ≥ 50 mL/min (Cockcroft and Gault formula)
- Albumin > 1x 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
- Patient with life expectancy > 3 months
8. Male or female patient, age ≥18 years
9. Patient with a BMI > 18 kg/m² and >40 kg
10. Male patient or female patient of childbearing potential must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception (with failure rate < 1%) 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 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.
14. 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.

E.4

Principal exclusion criteria

1. Patient treated for a cancer other than pancreatic cancer within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ
2. Patient with no pain related to the disease (as defined in the inclusion criterion number 2) and no genetic fingerprint of aggressiveness
3. Patient with ECOG ≥ 2
4. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
5. 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
6. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
7. Pregnant, intent to be pregnant, or nursing female patient.

E.5 End points

E.5.1

Primary end point(s)

Overall survival (OS)

E.5.1.1

Timepoint(s) of evaluation of this end point

Defined as time from first randomisation to date of documented death.

E.5.2

Secondary end point(s)

1 Survival rate is defined as the rate of patients alive at each time point.
2. 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.
3. PFS rate is defined as the rate of patients without progression or death at each time point. Progression is assessed by CT scan.
4. Overall Time to progression (TTP) is defined as the time from the date of randomization to the date of documented progression.
5. TTP rate is defined as the rate of patients without documented progression.
6. Best Response is defined as the best response from baseline (CR or PR or SD or PD) assessed by CT Scan.
7. 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.
8. Change in percentage and in absolute value for the level of serum CA 199 between baseline and at each time point.

E.5.2.1

Timepoint(s) of evaluation of this end point

Survival rate every 24 weeks.
Progression Free Survival (PFS) every 8 weeks.
Quality of life assessments every 4 weeks until week 48 then 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

E.6.11

Pharmacogenomic

Yes

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

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Study is double-randomised with two parallel groups

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

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

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

Austria

Belgium

Brazil

Canada

China

Czech Republic

Greece

Hong Kong

Hungary

India

Korea, Republic of

Malaysia

Mexico

Morocco

Peru

Philippines

Poland

Romania

Russian Federation

Singapore

South Africa

Spain

Tunisia

Ukraine

United Kingdom

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, limiting toxicity or withdrawal of consent. Follow up continued until death of patient

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