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: 30 June 2019
• Main ID: EUCTR2013-002293-41-DE
• Date of registration: 18/02/2014
• 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: 07/04/2015
• Target sample size: 549
• Recruitment status: Not Recruiting
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Cornelia Franke
• Affiliation: AB Science

• Name: Cornelia Franke
• Affiliation: AB Science

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically or cytologically confirmed adenocarcinoma of the pancreas, non resectable locally advanced or metastatic stage, 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. 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 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 = 2
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
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. Acceptable forms of contraception include:
• A documented placement of an intrauterine device (IUD) or intrauterine 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 (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
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 s
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 = 3
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
8. Patient eligible to Folfirinox treatment

SAFETY RULES FOR SECOND RANDOMISATION
• If patients discontinued for safety reasons related to study treatment or reasons not assessable, the patients cannot be re-randomized.
• If patient’s dose of study treatment was reduced for safety reasons and patient had progressed at the dose reduced, the patients will be re-randomized at the last reduced dose tolerated.
The second randomisation will only be made at the last dose of masitinib or placebo treatment received during the first randomisation. This is the dose that the patient tolerated in the first randomisation phase.
• If patients are ongoing with a grade 2 or grade 3 AE and progressed, patients cannot be re-randomized while having AE.
The outcome of grade 2 or grade 3 AE might be:
- Discontinuation. In this case patients will not be re-randomized (see before).
- Dose reduction and the reduced dose is tolerated. In this case patients will be re-randomized in case of progression at this reduced tolerated dose (see before).
- Return to baseline or grade 1 with no dose reduction and the reduced dose is tolerated. In this case patients will be re-randomized at this tolerated dose in case of progression.
• Patient having presented with disabling or life-threatening adverse event due to first line treatment will be excluded.

Those patients who according to the assessment of the PI would benefit more from an alternative therapy will continue to be excluded from the second randomi

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

Health Condition(s) or Problem(s) studied

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

Non resectable locally advanced or metastatic pancreatic cancer
MedDRA version: 18.1 Level: PT Classification code 10033610 Term: Pancreatic carcinoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: masitinib 100mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: MASITINIB MESYLATE
CAS Number: 1048007-93-7
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 200mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: MASITINIB MESYLATE
CAS Number: 1048007-93-7
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

Primary Outcome(s)

Main Objective: Overall survival (OS)

Secondary Objective: • 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.
• PFS rate is defined as the rate of patients without progression or death at each time point. Progression is assessed by CT scan.
• Overall Time To Progression (TTP) is defined as the time from the date of randomization to the date of documented progression
• TTP rate is defined as the rate of patients without documented progression .
• Best response is defined as the best response from baseline (CR or PR or SD or PD) assessed by CT scan.
• 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.
• Change in percentage and in absolute value for the level of serum CA 19-9 between baseline and at each time point.

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)

Timepoint(s) of evaluation of this end point: Every 8 weeks

Secondary end point(s): Progression Free Survival

Secondary ID(s)

AB12005

2013-002293-41-CZ

Source(s) of Monetary Support

AB Science

Ethics review

Status: Approved
Approval date:
Contact: