A prospective, multicentre, open-label, randomised, uncontrolled, phase 1/2 study to evaluate efficacy and safety of masitinib in combination with etoposide, or masitinib in combination with irinotecan in patients with advanced hepatocellular carcinoma and who relapsed after a first line therapy with sorafenib.

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2010-022620-77-FR
• Date of registration: 01/10/2010
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: A prospective, multicentre, open-label, randomised, uncontrolled, phase 1/2 study to evaluate efficacy and safety of masitinib in combination with etoposide, or masitinib in combination with irinotecan in patients with advanced hepatocellular carcinoma and who relapsed after a first line therapy with sorafenib.
• Scientific title: A prospective, multicentre, open-label, randomised, uncontrolled, phase 1/2 study to evaluate efficacy and safety of masitinib in combination with etoposide, or masitinib in combination with irinotecan in patients with advanced hepatocellular carcinoma and who relapsed after a first line therapy with sorafenib.
• Date of first enrolment: 15/07/2013
• Target sample size: 36
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022620-77
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: masitinib in combination with other medicinal product in each group
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, France, Greece, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient with histologically or cytologically confirmed advanced-stage hepatocellular carcinoma (HCC) (unresectable, and/or metastatic) or responding to the Barcelona diagnostic criteria
2. Patient who have discontinued from first line treatment with sorafenib monotherapy for any reason (ie, tumor disease progression, intolerance) at least 14 days prior to planned randomization but have not received any second line treatment for HCC
3. Patient who have recovered from any significant sorafenib-related treatment toxicities prior to randomization (=Grade 2)
4. Patient with at least one untreated target lesion that could be measured in one dimension, according to the Response Evaluation Criteria in Solid Tumors (RECIST)
5. Patients who have received local therapy prior to sorafenib administration (radiation, surgery, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection [PEI] or cryoablation) are eligible. Local therapy must be completed at least 4 weeks prior to the baseline scan
6. Adequate antiviral systemic therapy in sympotomatic and asymptomatic HBV Ag carriers
7. Patient eligible for receiving a second line treatment including etoposide and irinotecan
8. Child-Pugh liver function class A
9. Barcelona Clinic Liver Cancer (BCLC) classification: class C
10. Eastern Cooperative Oncology Group (ECOG) Performance Status = 2
11. Patient with adequate organ function:
• Absolute Neutrophil Count (ANC) = 1.5 x 109/L
• Haemoglobin = 10 g/dL
• Platelets (PTL) = 85 x 109/L
• AST/ALT = 5 x ULN
• Gamma-GT = 5 x ULN
• Bilirubin = 1.5 x ULN
• Creatinin clearance = 50 mL/min (Cockcroft and Gault formula)
• Albumin > LLN
• Urea = 2 x ULN
• Proteinuria < 30 mg/dL; in case of proteinuria = 30 mg/dL on the dipstick, 24 hours proteinuria < 1.5g/24 hours
12. Patient with life expectancy = 3 months
13. Female or male patient = 18 years
14. Patient weight > 40 kg and BMI > 18
15. Female patient of child bearing potential who agrees to use a method of medically acceptable forms of contraception during the study and 3 months after the last intake of study treatment
16. Patient able and willing to comply with study visits and procedures as per protocol
17. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures are performed
18. Patient affiliated to a social security regimen

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Patient intolerant to etoposide or irinotecan
2. Patient who have received a liver transplant
3. Patient with clinically significant symptoms of hepatic encephalopathy
4. Patient who have received a previous systemic therapy (including investigational agents) other than sorafenib (see Inclusion Criterion 2) for treatment of HCC. Patients participating in surveys or observational studies are eligible to participate in this study
5. Patient who have had treatment with any of the following within the specified timeframe prior to randomization:
• Any sorafenib within the 14 days prior to randomization
• Major surgery within the 4 weeks prior to randomization
• Any transfusion, treatment with blood component preparation, received erythropoietin , albumin preparation, and granulocyte colony-stimulating factor (G CSF) within the 2 weeks prior to randomization
6. Patient with previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to entry is permitted
7. Patient presenting with at least one of the following condition:
- Ischemic heart disease, defined by at least one of the following condition:
a. Medical history of ischemic heart disease
b. Clinical symptoms of ischemic heart disease
c. Q wave > 3 mm on the electrocardiogram
d. ST elevation or depression > 2 mm on the electrocardiogram
e. Negative T wave in at least 2 leads of the electrocardiogram
- Cardiac failure, defined by at least one of the following condition:
a. Medical history of cardiac failure defined by a previous left ventricular ejection fraction = 50%
b. Clinical symptoms of cardiac failure
c. Current treatment for cardiac failure
d. NT Pro-BNP = 300 pg/mL or BNP = 75 pg/mL and/or troponin T > 0.1 ng/mL or troponin I > 0.35 ng/mL
- Conduction disorders or arrhythmia, defined by at least one of the following and confirmed by electrocardiogram:
a. Severe ventricular arrhythmia (frequent premature ventricular beats)
b. Atrioventricular block at second or third level
c. Left bundle branch block
8. Pregnant or nursing female patient
9. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
10. 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.
Previous treatment
11. Patient treated with any investigational agent within 4 weeks prior baseline



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

Health Condition(s) or Problem(s) studied

hepatocellular carcinoma
MedDRA version: 12.1 Level: LLT Classification code 10019830 Term: Hepatocellular carcinoma resectable
MedDRA version: 12.1 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable
MedDRA version: 12.1 Level: LLT Classification code 10019829 Term: Hepatocellular carcinoma recurrent

Intervention(s)

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number: 790-29979-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Toposar®, VePesid®, Etopophos®
Product Name: etoposide
Pharmaceutical Form: Solution for infusion
CAS Number: 117091642
Other descriptive name: ETOPOSIDE PHOSPHATE
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 60-
INN or Proposed INN: ETOPOSIDE
CAS Number: 33419420
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 45-

Trade Name: Camptosar
Product Name: irinotecan
Pharmaceutical Form: Solution for injection
INN or Proposed INN: IRINOTECAN
CAS Number: 97682445
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 350-
INN or Proposed INN: IRINOTECAN
CAS Number: 97682445
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 262.5-

Primary Outcome(s)

Secondary Objective: Survival
- Overall survival (OS)
- Survival rate at week 6, 12, 18, 24
- PFS rate at week 6, 12, 18, 24
Tumour assessment:
- Overall Time to progression (TTP)
- Objective response rate (CR + PR) at week 6, 12, 18, 24
- Control disease rate (CR + PR + SD) at week 6, 12, 18, 24
- Best response during study treatment
- Time to response
- Quality of life assessment according to the EORTC QLQ-C30 questionnaire at week 6, 12, 18, 24
- ECOG Performance Status

Safety profile using the NCI CTC v4.02 classification

Pharmacokinetics

Main Objective: Overall Progression Free Survival (PFS)

Primary end point(s): Progression Free Survival (PFS) is defined as the time from the randomization to the date of documented progression or any cause of death during the study. Progression will be assessed by CT scan according to Modified-RECIST criteria version 1.1.

Secondary ID(s)

AB10006

Ethics review

Status: Approved
Approval date:
Contact: