A study to compare masitinib in combination with irinotecan to placebo in combination with irinotecan in the treatment of patients with esophagogastric adenocarcinoma
- Conditions
- ?atients with advanced-stage esophagogastric adenocarcinoma who have relapsed after first-line chemotherapyMedDRA version: 18.1Level: LLTClassification code 10017778Term: Gastric carcinoma stage IV without metastasesSystem Organ Class: 100000004864MedDRA version: 18.1Level: LLTClassification code 10017776Term: Gastric carcinoma stage IIISystem Organ Class: 100000004864MedDRA version: 18.1Level: LLTClassification code 10017777Term: Gastric carcinoma stage IV NOSSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2015-000897-36-GR
- Lead Sponsor
- AB science
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 364
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 < 30 mg/dL (1+) on the dipstick; if proteinuria is = on the dipstick, 24 hours proteinuria must be <1.5g/24 hours
•Troponin T < 0.1 ng/mL or Troponin I < 0.35 ng/mL
8.Female or Male patient = 18 years
9.Patient with life expectancy = 3 months
10.Patient weight > 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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: every 8 weeks;Secondary end point(s): •Survival rate every 8 weeks<br>•Tumor assessment<br>-Overall Progression Free Survival (PFS)<br>-PFS rate every 8 weeks<br>-Overall Time To Progression (TTP)<br>-TTP rate every 8 weeks<br>-Best response rate, Objective response rate (CR + PR) and Disease control rate (CR + PR + SD) every 8 weeks<br>•Quality of life assessment every 8 weeks <br>-ECOG Performance Status improvement or stabilisation<br>-Quality of Life according to the EORTC QLQ-C30<br>-Pain reduction (VAS)<br>•Pharmacogenomic assessment (Relationship between genomic data and overall survival)<br>•Safety profile using the NCI CTCAE v4.02 classification<br>