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: 10 December 2019
• Main ID: EUCTR2013-002293-41-SK
• Date of registration: 19/02/2014
• 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: 15/05/2014
• 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, Singapore, Slovakia, South Africa, Spain, Tunisia, Ukraine, United Kingdom, United States

Contacts

• Name: Elena Carmen RADU
• Affiliation: AB Science

• Name: Elena Carmen RADU
• Affiliation: AB Science

Key inclusion & exclusion criteria

Inclusion criteria:
First randomisation 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 and 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 agree to 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 m
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
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: 20.0 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 100mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
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
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: Overall survival (OS)

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

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.

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: