?atients with advanced-stage esophagogastric adenocarcinoma who have relapsed after first-line chemotherapy MedDRA version: 18.1 Level: LLT Classification code 10017776 Term: Gastric carcinoma stage III System Organ Class: 100000004864 MedDRA version: 18.1 Level: LLT Classification code 10017777 Term: Gastric carcinoma stage IV NOS System Organ Class: 100000004864 MedDRA version: 18.1 Level: LLT Classification code 10017778 Term: Gastric carcinoma stage IV without metastases System Organ Clas
Conditions
Interventions
Product Name: Masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
CAS Number: 790-299-79-5
Other descriptive name: MASITINIB MESYLATE
Concentration unit: mg milligram(s)
Concentrati
Sponsors
AB science
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient with histologically or cytologically advanced-stage, recurrent esophagogastric adenocarcinoma (unresectable, and/or metastatic) 2. Patient has failed to one prior cycle cancer therapy (radiotherapy, chemotherapy, chemoradiotherapy or targeted therapy given > 4 weeks prior to baseline). Failure is defined either by progression of disease or by significant toxicity that precludes further treatment. A patient who has documented metastasis after resection and adjuvant therapy is eligible for the study. 3. Patient has recovered of all acute toxic side effects of prior therapy or surgical procedures to grade = 1 National Cancer Institute-Common Toxicity Criteria (NCI-CTCAE), except for the laboratory values 4. Patient is eligible for a second line treatment with irinotecan 5. Patient has at least one target lesion that can be measured in one dimension, according to the Response Evaluation Criteria in Solid Tumors (RECIST) 6. ECOG Performance status = 2 7. 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 =3 x ULN (=5 x ULN in case of liver metastases) • Gamma-GT = 2.5 x ULN (=5 x ULN in case of liver metastases) • Bilirubin =1.5 x ULN (=3x ULN in case of liver metastases) • Normal creatinine or if abnormal creatinine, creatinin clearance =50 mL/min (Cockcroft and Gault formula) • Albumin >1 xLLN • Proteinuria 40 kg and BMI > 18 kg/m² 11. Patient with nutritional risk index (NRI) = 83.5, i.e. with no or moderate malnutrition; NRI is calculated as follows: NRI = 1.519 x serum albumin level (g/L) + 0.417 x (current weight (kg) / basic weight (kg)) x 100 12. Female patient of childbearing potential (entering the study after a menstrual period and who has 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. 13. Patient is able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures 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 must sign the informed consent 14. 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 15. 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 164 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: 1. Patient intolerant to irinotecan 2. Patient previously treated with more than one prior systemic regimen for the treatment of esophagogastric cancer including chemotherapy and/or targeted anticancer therapy 3. Patient who had radiotherapy within 4 weeks before baseline 4. Patient who had major surgery within 4 weeks before the start of study treatment (central venous access device placement is not considered major surgery) 5. Patient who has not recovered from any significant treatment toxicities prior to baseline (= Grade 2) 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 hypertension or symptomatic hypertension, where hypertension is defined by systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg and uncontrolled means that SBP lower than 140 mmHg and DBP lower than 90 mmHg are not achieved despite anti-hypertensive drugs, whatever the reason of failure (inadequate treatment, poor compliance, secondary hypertension or resistant hypertension). • Patient with co-existing dermatological disease (e.g. eczema, psoriasis) or history of skin allergy • Patient presenting with oedemas • Patient with chronic diarrhea 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 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 WASH OUT 10. Patient treated with any investigational agent within 4 weeks prior baseline
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate efficacy in tearms of Overall Survival of masitinib with irinotecan in patients with advanced-stage esophagogastric adenocarcinoma who have relapsed after first-line chemotherapy.;Secondary Objective: Secondary objectives are to evaluate the complementary efficacy (Progression Free Survival and Tumor Response) and safety in each group of patients with advanced-stage esophagogastric adenocarcinoma who have relapsed after first-line chemotherapy.;Primary end point(s): Overall survival (OS) ;Timepoint(s) of evaluation of this end point: Not Applicable | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Survival rate every 8 weeks • Tumor assessment - Overall Progression Free Survival (PFS) - PFS rate every 8 weeks - Overall Time To Progression (TTP) - TTP rate every 8 weeks - Best response rate, Objective response rate (CR + PR) and Disease control rate (CR + PR + SD) every 8 weeks • Quality of life assessment every 8 weeks - ECOG Performance Status improvement or stabilisation - Quality of Life according to the EORTC QLQ-C30 - Pain reduction (VAS) • Pharmacogenomic assessment (Relationship between genomic data and overall survival) • Safety profile using the NCI CTCAE v4.02 classification ;Timepoint(s) of evaluation of this end point: every 8 weeks | — |
Countries
Brazil, European Union, Greece, Peru
Contacts
Public ContactLaurent Guy
AB science
Outcome results
None listed