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

Phase 1

• Conditions: 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]

• Registration Number: EUCTR2010-022620-77-ES
• Lead Sponsor: AB Science

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-10-30
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 36

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified