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

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2010-022620-77-ES
• Date of registration: 30/10/2014
• 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: 03/02/2015
• 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; 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

Contacts

• Name: Consuelo Pozo
• Affiliation: Alpha Bioresearch, S.L

• Name: Consuelo Pozo
• Affiliation: Alpha Bioresearch, S.L

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient with histologically or cytologically confirmed advanced-stage hepatocellular carcinoma (unresectable, and/or metastatic) or responding to the Barcelona diagnostic criteria
2. Patient who has received sorafenib single agent as first 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 one 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 one untreated target lesion that could be measured in one dimension:
? according to the Response Evaluation Criteria in Solid Tumors (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 [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 symptomatic and asymptomatic HBV Ag carriers
7. Patient eligible for receiving etoposide and irinotecan (either as a second line treatment after sorafenib or first line for patient not previously treated with sorafenib)
8. Child-Pugh liver function class A (see following page)
9. Eastern Cooperative Oncology Group (ECOG) Performance Status ? 2
10. Patient with adequate organ function:
? 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
? Total bilirubin ? 3x ULN
? Normal Creatinine or if abnormal creatinine, creatinine clearance ? 50 mL/min (Cockcroft and Gault formula)
? Albumin ? 0.75 LLN
? Proteinuria < 30 mg/mL (1+) on the dipstick. If proteinuria is ? 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hour
11. life expectancy > 3 months
12. patient ? 18 years
13. Patient weight > 40 kg and BMI > 18 kg/m²
14. Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), 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.
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.
Male patients must use two highly effective methods (one for the patient and
Exclusion criteria:
A patient must not be enrolled if he (she) fulfills one of the following 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

Hepatocellular carcinoma
MedDRA version: 17.1 Level: LLT Classification code 10019829 Term: Hepatocellular carcinoma recurrent System Organ Class: 100000004864
MedDRA version: 17.1 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 100000004864
MedDRA version: 17.1 Level: LLT Classification code 10019830 Term: Hepatocellular carcinoma resectable System Organ Class: 100000004864

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: 790-29979-5
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
INN or Proposed INN: ETOPOSIDE
CAS Number: 117091642
Current Sponsor code: ETOPOSIDE
Other descriptive name: ETOPOSIDE
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 60-
INN or Proposed INN: ETOPOSIDE
CAS Number: 33419420
Current Sponsor code: ETOPOSIDE
Other descriptive name: ETOPOSIDE
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: 180-
INN or Proposed INN: IRINOTECAN
CAS Number: 97682445
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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 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 weeks 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 weeks after.
o Best response during study treatment
o Alpha fetoprotein dosage at week 6, 12, 18, 24 and every 12 weeks after.
? Safety profile using the NCI CTC v4.02 classification
? Pharmacokinetics
? Phenotypic Analysis of selected genes

Timepoint(s) of evaluation of this end point: week 6, 12, 18, 24 and every 12 weeks

Secondary Outcome(s)

Secondary end point(s): 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 weeks 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 weeks after.
o Best response during study treatment
o Alpha fetoprotein dosage at week 6, 12, 18, 24 and every 12 weeks after.
? Safety profile using the NCI CTC v4.02 classification
? Pharmacokinetics
? Phenotypic Analysis of selected genes

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

Secondary ID(s)

AB10006

2010-022620-77-FR

Source(s) of Monetary Support

AB Science

Ethics review

Status: Approved
Approval date:
Contact: