Study to evaluate 2 types of treatment as first line treatment (masitinib + gemcitabine or placebo + gemcitabine ) and 2 types of treatment as second line treatment (masitinib + FOLFIRI 3 or placebo + FOLFIRI 3) in the treatment of patients with with non resectable locally advanced or metastatic pancreatic cancer.

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2013-002293-41-GR
• Date of registration: 24/02/2014
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: Study to evaluate 2 types of treatment as first line treatment (masitinib + gemcitabine or placebo + gemcitabine ) and 2 types of treatment as second line treatment (masitinib + FOLFIRI 3 or placebo + FOLFIRI 3) in the treatment of patients with with non resectable locally advanced or metastatic pancreatic cancer.
• Scientific title: 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.
• Date of first enrolment: 22/05/2015
• Target sample size: 549
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002293-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Austria, Belgium, Brazil, Canada, China, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, India, Italy, Korea, Republic of, Malaysia, Mexico, Morocco, Peru, Philippines, Poland, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Tunisia, Ukraine, United Kingdom, United States

Contacts

• Name: Denys ZAITSEV
• Affiliation: AB Science

• Name: Denys ZAITSEV
• Affiliation: AB Science

Key inclusion & exclusion criteria

Inclusion criteria:
First randomisation:
1. Histologically or cytologically confirmed adenocarcinoma of the pancreas, non resectable locally advanced or metastatic stage
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 > 20mm on Visual Analogue Scale at screening or baseline.
OR
Patient treated with opioid analgesics at dose = 1 mg/kg/day
OR
Patients with ‘genetic fingerprint of aggressiveness ACOX1 (DCt = 3.05)
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 = 5x ULN
• Gamma GT = 5x ULN
• Bilirubin = 3x ULN
• Normal Creatinine or if abnormal creatinine, CrCl=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
8. Patient with life expectancy > 3 months
9. Male or female patient, age ?18 years
10. Patient with a BMI > 18 kg/m² and >40 kg
11. Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test at screening and baseline), 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. These include:
• A documented placement of an intrauterine device (IUD) or system (IUS) and the use of a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository)
• Documented tubal ligation (female sterilization). In addition, a barrier method used with spermicidal should also be used
• Double barrier method: Condom and occlusive cap with spermicidal
• Any other contraceptive method with a failure rate of <1% per year
• Abstinence
12. Male patients must use medically acceptable methods of contraception if your female partner is pregnant, from the time of the first administration of the study drug until three months following administration of the last dose of study drug. These include:
• Condom;
• If the patient has undergone surgical sterilization (vasectomy with documentation of azoospermia) a condom should also be used.
Male patients must 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. These are:
• Condom and occlusive cap with spermicidal foam/gel/film/cream/suppository;
• Surgical sterilization (vasectomy with documentation of azoospermia) and a barrier method used with spermicidal;
• The female partner uses oral contraceptives (combination oestrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier
Exclusion criteria:
First randomisation 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
WASH OUT & PREVIOUS TREATMENT
1. Any anti-tumour therapy (any chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy) within 6 months prior to baseline
2. Treatment with any investigational agent within 4 weeks prior to baseline
3. Patients with an active infection requiring antibiotics within 14 days prior to registration

Second randomisation exclusion criteria:
1. Patient intolerant to masitinib
The patient is considered as intolerant to masitinib if he/she presented with a severe adverse event (grade = 3) due to the mechanism of action of masitinib (i.e. rash, nausea, vomiting or diarrhea) which led to interruption and/or dose reduction of first line treatment followed by a re-challenge of first line treatment leading to the same severe adverse event.
2. Patient having presented with disabling or life-threatening adverse event due to first line treatment



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non resectable locally advanced or metastatic pancreatic cancer after
MedDRA version: 18.0 Level: PT Classification code 10033610 Term: Pancreatic carcinoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib, mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: MASITINIB MESYLATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib, mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: MASITINIB MESYLATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: GEMZAR
Product Name: Gemcitabine
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 1000-

Trade Name: IRINOTECAN/GENERICS
Product Name: Irinotecan
Product Code: INEOF00997
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: IRINOTECAN
CAS Number: 97682-44-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: LEUCOVORIN/PFIZER
Product Name: Calcium Folinate
Pharmaceutical Form: Solution for injection
INN or Proposed INN: CALCIUM FOLINATE
CAS Number: 1492-18-8
Other descriptive name: ANHYDROUS CALCIUM FOLINATE
Concentration unit: mg/l milligram(s)/litre
Concentration type: equal
Concentration number: 200/20-

Trade Name: URACIFLOR
Product Name: 5-FLUOROURACIL
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: FLUOROURACIL SODIUM
CAS Number: 66048-65-1
Other descriptive name: 5-FU
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concen

Primary Outcome(s)

Secondary Objective: 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.

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

Primary end point(s): • Overall Survival (OS) is defined as the time from the randomization to the date of documented death

Timepoint(s) of evaluation of this end point: Date of documented death

Secondary Outcome(s)

Secondary end point(s): 1. Survival rate every 24 weeks
2. Tumour assessment:
- Overall Progression Free Survival (PFS) central and local
- PFS rate every 8 weeks,
- Time To Progression (TTP) central and local
- TTP rate every 8 weeks central and local
- Overall Time to Progression (TTP) according to RECIST 1.1
- TTP rate every 8 weeks according to RECIST 1.1
- Overall Time to Treatment switch (TTS)
- TTS rate every 8 weeks
- Best response along study: Complete response (CR) rate, Partial Response (PR) rate, Progressive disease (PD) every 8 weeks
- Level of serum CA 19-9 every 8 weeks
3. Quality of life assessment:
- EORTC QLQ-C30 questionnaire every 4 weeks until week 48 then every 8 weeks
- ECOG Performance Status every 4 weeks until week 48 then every 8 weeks
- Patient’s visual analogue scale (VAS) and Brief Pain Inventory (BPI) every 4 weeks until week 48 then every 8 weeks
- Analgesic consumption every 4 weeks until week 48 then every 8 weeks
4. Safety profile using the NCI CTC v4.02 classification
- Discontinuation for related adverse event
-Related Grade 3 non haematological or any related grade 4 related adverse event
-Adverse events leading to death
-Cardiac adverse events
-Adverse events related to cancer pain: abdominal pain, back pain…

Timepoint(s) of evaluation of this end point: 1. every 24 weeks
2. every 8 weeks
3. every 4 weeks until week 48 then every 8 weeks
4. per case & at the end of the study

Secondary ID(s)

2013-002293-41-BE

AB12005

Source(s) of Monetary Support

AB Science