Evaluation of safety and efficacy of masitinib combined with etoposide or irinotecan in patients with relapsing liver cancer

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2010-022620-77-GR
• Date of registration: 06/08/2015
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: Evaluation of safety and efficacy of masitinib combined with etoposide or irinotecan in patients with relapsing liver cancer
• 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: 16/11/2015
• Target sample size: 34
• 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: no; 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: no; Number of treatment arms in the trial: 2
• 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, Slovakia, Spain, United States

Contacts

• Name: Christine PELVIN
• Affiliation: AB Science

• Name: Christine PELVIN
• Affiliation: AB Science

Key inclusion & exclusion criteria

Inclusion criteria:
1. ?istologically or cytologically confirmed advanced-stage hepatocellular carcinoma (HCC) (unresectable, and/or metastatic) or responding to the Barcelona diagnostic criteria
2. Patient who has received sorafenib single agent as 1st line treatment and had discontinued from this treatment for any reason (ie, tumor disease progression, intolerance) at least 14 days prior to baseline (A line of treatment is defined as at least 1 prior therapeutic regimen consisting of chemotherapy or biologic agent). Requirement for sorafenib treatment is not applicable to patients who have not been previously treated with sorafenib for any reason (e.g., contra-indication to sorafenib, patient refusal to sorafenib treatment due to expected toxicity, etc.)
3. Patient who has recovered from any significant sorafenib-related treatment toxicities prior to baseline (=Grade 2)
4. Patient with at least 1 untreated target lesion that could be measured in 1 dimension:
• according to the RECIST 1.1
• and according to Modified RECIST assessment for hepatocellular carcinoma
5. Patient who has received local therapy prior to sorafenib administration (surgery, hepatic arterial embolization, chemoembolization, radioembolisation, radiofrequency ablation, percutaneous ethanol injection or cryoablation) are eligible. Local therapy must be completed at least 4 weeks prior to the baseline scan
6. Adequate antiviral systemic therapy in symptomatic and asymptomatic HBV Ag carriers
7. Patient eligible for receiving etoposide and irinotecan (either as a 2nd line treatment after sorafenib or 1st line for patient not previously treated with sorafenib)
8. Child-Pugh liver function class A
9. Barcelona Clinic Liver Cancer classification: class C
10. ECOG Performance Status = 2
11. Patient with adequate organ function:
• ANC = 1.5 x 109/L
• Hb = 10 g/dL
• Platelets = 75 x 109/L
• AST/ALT = 5 x ULN
• ?GT = 5 x ULN
• Total bilirubin = 3 x ULN
• Normal Creatinine or if abnormal creatinine, creatinine clearance = 50 mL/min (Cockcroft and Gault formula)
• Albumin = 0.75 x LLN
• Urea < 2 x ULN
• Proteinuria < 30 mg/mL (1+) on the dipstick. If proteinuria is = 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hour
12. Patient with life expectancy > 3 months
13. = 18 years
14. weight > 40 kg and BMI > 18 kg/m²
15. Female patient of childbearing potential, who agrees to use 2 highly effective methods (1 for the patient and 1 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 IUD or IUS and the use of a barrier method used with spermicidal
foam/gel/film/cream/suppository)
• Documented tubal ligation (female sterilization). In addition, a barrier method should also be used
• Double barrier method: Condom and occlusive cap with spermicidal foam/gel/film/cream/suppository
• Any other con
Exclusion criteria:
1. Patient intolerant to etoposide or irinotecan
2. Patient who has received a liver transplant
3. Patient with clinically significant symptoms of hepatic encephalopathy
4. Patient who has previously received more than two line of systemic therapy. One previous therapy must at least be with sorafenib monotherapy unless the patient has not been treated with sorafenib for any reason (e.g. contra-indication to sorafenib, patient refusal to sorafenib due to expected toxicity, etc.) (See Inclusion Criterion 2). Patients participating in surveys or observational studies are eligible to participate in this study.
5. 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 > 5 years prior to entry is permitted
6. 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
7. Pregnant or nursing female patient
8. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
9. Patient with history of poor compliance, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent.
WASH OUT
10. Patient treated with any investigational agent within 4 weeks prior baseline
11. Patient who has had treatment with any of the following within the specified timeframe prior to baseline:
• Any sorafenib within the 14 days prior to baseline
• Major surgery within the 4 weeks prior to baseline
• Any transfusion, treatment with blood component preparation, received erythropoietin, albumin preparation, and granulocyte colony-stimulating factor (G CSF) within the 2 weeks prior to baseline


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

Health Condition(s) or Problem(s) studied

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

Hepatocellular carcinoma
MedDRA version: 18.1 Level: LLT Classification code 10019829 Term: Hepatocellular carcinoma recurrent System Organ Class: 100000004864
MedDRA version: 18.1 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 100000004864
MedDRA version: 18.1 Level: LLT Classification code 10019830 Term: Hepatocellular carcinoma resectable System Organ Class: 100000004864

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-

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
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: ETOPOSIDE/PHARMACHEMIE
Product Name: Etoposide
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Etoposide
CAS Number: 117091642
Other descriptive name: ETOPOSIDE PHOSPHATE
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 50-

Trade Name: IRINOTECAN/DEMO
Product Name: Irinotecan
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: IRINOTECAN
CAS Number: 97682445
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Main Objective: Overall Survival (OS)

Primary end point(s): Overall Survival (OS) defined as the time from randomisation to the date of death from any cause

Secondary Objective: • Survival rate at week 6, 12, 18, 24 and every 12 weeks after
• Overall Progression Free Survival (PFS) according to RECIST version 1.1 and according to Modified RECIST (mRECIST) assessment for hepatocellular carcinoma
• PFS rate at week 6, 12, 18, 24 and every 12 weeks after, according to RECIST version 1.1. and to mRECIST assessment for hepatocellular carcinoma
• Tumour assessment, first according to RECIST version 1.1. and secondly according to mRECIST assessment for hepatocellular carcinoma:
o Overal Time to progression (TTP)
o TTP rate at week 6, 12, 18, 24 and every 12 wks after
o Objective response rate (CR + PR) at week 6, 12, 18, 24 and every 12 weeks after
o Control disease rate (CR + PR + SD) at week 6, 12, 18, 24 and every 12 wks after
o Best response during study treatment
o Alpha fetoprotein dosage at week 6, 12, 18, 24 and every 12 wks after
• Safety profile using the NCI CTC v4.02 classification
• Pharmacokinetics
• Phenotypic Analysis of selected genes

Timepoint(s) of evaluation of this end point: From randomisation to the date of death from any cause

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: W6, W12, W18, W24 and every 12 weeks

Secondary end point(s): - Survival rate at week 6, 12, 18, 24 and every 12 weeks
- Overall PFS according to Modified RECIST (mRECIST) assessment for hepatocellular carcinoma
- PFS rate at week 6, 12, 18, 24 and every 12 weeks according to RECIST version 1.1. and to mRECIST assessment for hepatocellular carcinoma
- Tumour assessment, first according to RECIST version 1.1. and secondly according to mRECIST assessment for hepatocellular carcinoma:
- Overall Time to progression (TTP)
- Objective response rate (CR + PR) at week 6, 12, 18, 24 and every 12 weeks
- Control disease rate (CR + PR + SD) at week 6, 12, 18, 24 and every 12 weeks
- Best response during study treatment
- Alpha fœto protein dosage at week 6, 12, 18, 24 and every 12 weeks
- Safety profile using the NCI CTC v4.02 classification
- Pharmacokinetics
- Phenotypic analysis

Secondary ID(s)

AB10006

2010-022620-77-FR

Source(s) of Monetary Support

AB Science

Ethics review

Status: Approved
Approval date: 07/10/2015
Contact: