Clinical Trials Register

Summary
EudraCT Number:	2013-000491-14
Sponsor's Protocol Code Number:	AB12008
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2014-08-18
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

2013-000491-14

A.3

Full title of the trial

A prospective, multicenter, open-label, centrally allocated, active-controlled,
phase 2/3 study to evaluate the efficacy and safety of masitinib in combination with gemcitabine versus gemcitabine alone in advanced/metastatic epithelial ovarian cancer patients in second line being refractory to first line platinum treatment or in third line.

A.3.1

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

Evaluation of masitinib in patients with advanced ovarian cancer

A.3.2

Name or abbreviated title of the trial where available

Phase 2 comparing masitinib with gemcitabine in ovarian cancer v1

A.4.1

Sponsor's protocol code number

AB12008

A.5.4

Other Identifiers

Name:

IND Number

Number:

120579

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	Igor Antonshchuk/Project Manager
B.5.3	Address:
B.5.3.1	Street Address	AB Science, 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	33147209783
B.5.5	Fax number	33147202411
B.5.6	E-mail	igor.antonshchuk@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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Masitinib
D.3.2	Product code	AB 1010
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	Mastinib mesylate
D.3.9.1	CAS number	790-200-79-5
D.3.9.2	Current sponsor code	AB1010
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	equal
D.3.10.3	Concentration number	119 to 238
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Gemcitabine
D.2.1.1.2	Name of the Marketing Authorisation holder	Hospira UK Limited
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	Gemcitabine
D.3.4	Pharmaceutical form	Powder for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Gemcitabine
D.3.9.1	CAS number	95058-81-4
D.3.9.3	Other descriptive name	SUB07892MIG
D.3.9.4	EV Substance Code	AS3
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	750 to 1000
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced / metastatic epithelial ovarian cancer patients in second
line being refractory to first line platinum treatment or in third line

E.1.1.1

Medical condition in easily understood language

Advanced / metastatic ovarian cancer

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	PT
E.1.2	Classification code	10033158
E.1.2	Term	Ovarian epithelial cancer 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

E.2 Objective of the trial

E.2.1

Main objective of the trial

The objective is to compare the efficacy and safety of masitinib in combination with gemcitabine versus gemcitabine alone in advanced / metastatic epithelial ovarian cancer patients in second line being refractory to first line platinum treatment or in third line.

E.2.2

Secondary objectives of the trial

The primary endpoint is overall survival (OS) of the patient. Secondary objectives includes:
Secondary endpoints
• Survival rate every 6 months
• Progression Free Survival (PFS)
• PFS rate week every 8 weeks
• Time To Progression (TTP)
• TTP rate every 8 weeks
• Best response rate during the study,
• Disease control rate (CR + PR + SD)
• Tumor biomarkers levels (CA 125)
• Quality of Life every 8 weeks
• Pharmacogenomic assessment of selected genes
• Safety profile using the CTCAE v4.03 classification

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

1.Pharmacogenomic assessments (relationship between genomic data and all efficacy variables,survival and tumor assessment)
a)Blood sample.
This ancillary study is aimed at finding potential DNA mutations, amplification and/or deletion that might explain short or long survival, side effects and treatment response. RNA expression patterns will also be studied thorough RNA analyses performed on peripheral blood.
b) Biopsies.
The tumor biopsies of all patients participating to this study and willing to take part to this Pharmacogenomic study will be collected at baseline.

2.In case a patient experiences either severe neutropenia or severe skin toxicity, an optional Pharmacogenomic blood sample would be collected. A genetic analysis will be conducted in order to better understand why patients are presenting these side effects. The samples collected will be analysed for polymorphism (point mutations) in relation to neutropenia and skin toxicity reactions.

Biopsy analysis and blood sample collected due to neutropenia/skin toxicity are optional. RNA analysis is mandatory.

E.3

Principal inclusion criteria

1. Female patient, with histologically or cytologically confirmed advanced / metastatic epithelial ovarian cancer either:
a. first line platinum-refractory ovarian cancer (progression during first-line platinum-based chemotherapy)
b. first line platinum-resistant ovarian cancer (relapsing within 6 months after the end of first-line chemotherapy)
c. candidate to third line treatment (refractory or resistant to 2nd line platinum-based therapy or patients who progressed after other type of chemotherapy in 2nd line).
2. Patient has recovered of all acute toxic side effects of prior therapy or surgical procedures to grade ≤ 1 Common Toxicity Criteria for Adverse Event (CTCAE v4.03), except for the laboratory values
3. Patient has at least one target lesion that can be measured in one dimension, according to the Response Evaluation Criteria in Solid Tumors (RECIST)
4. ECOG Performance status ≤ 2
5. Patient with adequate organ function
a. Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
b. Haemoglobin ≥ 10 g/dl
c. Platelets (PLT) ≥ 75 x 109/L
d. AST and ALT ≤ 3 x ULN (≤ 5 x ULN in case of liver metastases)
e. Gamma GT ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastases)
f. Bilirubin ≤ 1.5x ULN (≤ 3xULN in case of liver metastases)
g. Normal Creatinine or if abnormal creatinine, creatinine clearance ≥ 50 mL/min (Cockcroft and Gault formula)
h. Albuminaemia > 1 x LLN
i. Proteinuria < 30 mg/dL (1+) on the dipstick. If proteinuria is ≥ 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours
6. Patient with life expectancy > 3 months
7. Patient weight> 40 kg and BMI > 18 Kg/m2
8. Female patient ≥ 18 years
9. Patient with nutritional risk index (NRI) ≥ 83.5, i.e. with no or moderate malnutrition; NRI is calculated as follows: NRI = 1.519 x serum albumin level + 0.417 x (current weight / basic weight) x 100
- serum albumin in g/L
- basic weight calculation with Lorentz formula for ideal BW for women: (height − 100) − ((height − 150)/2)
- serum albumin in g/L
- basic weight calculation with Lorentz formula for ideal BW for women: (height − 100) − ((height − 150)/2)
10. Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use two highly effective 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. Acceptable forms of contraception include:
· A documented placement of an intrauterine device (IUD) or intrauterine system (IUS) and the useof a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository);
· Documented tubal ligation (female sterilisation). In addition, a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal
foam/gel/film/cream/suppository) should also be used;
· Double barrier method: Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository;
· Any other contraceptive method with a documented failure rate of <1% per year;
· Abstinence when this is in line with the preferred and usual lifestyle of the patient.
11. Patient able and willing to comply with study visits and procedures as per protocol
12. Patient is able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures performed.
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.

E.4

Principal exclusion criteria

EXCLUSION CRITERIA
A patient must not be enrolled if she fulfils one of the following exclusion criteria:
1. Patient intolerant to gemcitabine
2. Patient who has not recovered from any significant treatment toxicities prior to baseline (≥Grade 2)
3. Patient presenting with cardiac disorders defined by at least one of the following conditions:
a) 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)
b) Patient with cardiac failure class III or IV of the NYHA classification
c) Patient with severe conduction disorders which are not prevented by permanent pacing (atrioventricular block 2 and 3, sino-atrial block)
d) Syncope without known aetiology within 3 months
e) Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
4. Pregnant or nursing female patient
5. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
6. Patient treated for a cancer other than epithelial ovarian cancer within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ
7. 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
WASH-OUT
1. Patient who had any major surgery within 4 weeks before baseline/W0
2. Patient treated with any investigational agent within 4 weeks prior baseline
3. Patient who had systemic chemotherapy within 4 weeks before baseline
4. Patient who had radiotherapy within 4 weeks before baseline

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

Time from baseline to documented death.

E.5.2

Secondary end point(s)

Secondary endpoints
• Survival rate every 6 months
• Progression Free Survival (PFS)
• PFS rate week every 8 weeks
• Time To Progression (TTP)
• TTP rate every 8 weeks
• Best response rate during the study,
• Disease control rate (CR + PR + SD)
• Tumor biomarkers levels (CA 125)
• Quality of Life every 8 weeks
- according to the EORTC QLQ-C30 questionnaire
- ECOG Performance Status
- Analgesic intake
- Pain improvement (VAS)
• Pharmacogenomic assessment of selected genes
• Safety profile using the CTCAE v4.03 classification

E.5.2.1

Timepoint(s) of evaluation of this end point

Disease control rate, CA 125 and Quality of Life will be evaluated at Baseline, Week 8 and every 8 Weeks after W 8 and at the end of study visit.

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)

Yes

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

Yes

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

Yes

E.8.1.7.1

Other trial design description

prospective, active-controlled, seamless adaptive

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

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

Austria

Czech Republic

France

Germany

Greece

Spain

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

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