Metastatic colorectal cancer after 1 previous line of treatment MedDRA version: 18.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
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
Other descriptive n
Sponsors
AB Science
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient with non-resectable metastatic colorectal cancer with histological or cytological documentation of adenocarcinoma of the colon or rectum 2. Metastatic disease not amenable to surgical resection with curative intent 3. Patient in second line treatment after progression according to RECIST criteria following administration of a standard chemotherapy regimen for treatment of metastatic disease 4. Patient with measurable lesions according to RECIST criteria (version 1.1) with spiral CT scan and defined as ?10 mm in longest diameter and 2X the slice thickness for extra nodal lesions and/or >15 mm in short axis diameter for nodal lesions 5. Patient eligible for a standard second line therapy with FOLFIRI 6. Patient with ECOG = 2 7. Patient with adequate organ function • Absolute neutrophils count (ANC) = 1.5 x 109/L • Haemoglobin = 10 g/dl • Platelets (PLT) = 75 x 109/L • AST/ALT = 3 x ULN (= 5 x ULN in case of liver metastases) • GammaGT = 2.5 x ULN (= 5 x ULN in case of liver metastases) • Bilirubin = 1.5 x ULN (= 3 x ULN in case of liver metastasis) • Normal Creatinine or if abnormal creatinine, creatinine clearance = 50 mL/min (Cockcroft and Gault formula) • Albumin > 1 x LLN • Proteinuria 3 months 9. Female or male patient = 18 10. Patient weight >40 kg and BMI > 18 kg/m2 11. Contraception • 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. these include: - A documented placement of an intrauterine device (IUD) or system (IUS) and the use of a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository) - Documented tubal ligation (female sterilization). In addition, a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal should also be used - Double barrier method: condom and occlusive cap with spermicidal - Any other contraceptive method with a documented failure rate of <1% per year - Abstinence when this is in line with the preferred and usual lifestyle of the patient. • Male patients must 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. These are as follows: - Condom and occlusive cap with spermicidal - Surgical sterilization (vasectomy with documentation of azoospermia) and a barrier method used with spermicidal - If his female partner uses oral contraceptives (combination oestrogen/progesterone pills), injectable progesterone or subdermal implants, in addition a barrier method used with spermicidal foam should also be used. - Medically prescribed topically-applied transdermal contraceptive patch and a barrier method used with spermicidal - If his female partner has undergone documented tubal ligation (female sterilization), in addition a barrier method used with spermicidal should also be used. - If his female partner has undergone documented placement of an intrauterine device (IUD) or system (IUS), in
Exclusion criteria
Exclusion criteria: 1. Patient intolerant to one of these treatments: irinotecan, 5-fluorouracil (5-FU), folinic acid 2. More than 1 prior chemotherapy regimens for metastatic colorectal cancer. 3. Pregnant, intent to be pregnant, or nursing female patient 4. Patient with any chronic inflammatory bowel disease 5. Patient treated for a cancer other than colorectal cancer within five years before enrollment, with the exception of basal cell carcinoma or cervical cancer in situ 6. Patient required to receive other therapy than FOLFIRI for second line metastatic colorectal cancer 7. Patient with an hepatic involvement > 50% 8. Patient with active central nervous system (CNS) metastasis or history of CNS metastases 9. Patient with an active infection (Human immunodeficiency virus infection and/or hepatitis B or C infection …) 10. 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 11. Patient with a history of poor compliance or of drug/alcohol abuse, or excessive alcohol beverage consumption, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent WASH OUT 12. Any previous treatment with an investigational agent or chemotherapy or biological agent will require a wash-out period of four weeks prior to baseline.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Overall survival (OS);Secondary Objective: 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 at week every 8 weeks - ECOG Performance Status - Quality of Life according to the EORTC QLQ-C30 - Analgesic intake - Pain improvement (VAS) • Pharmacogenomic assessment (Relationship between genomic data and overall survival) • Safety profile using the CTCAE v4.03 classification ;Primary end point(s): Overall Survival (OS) is defined as the time from the randomization to the date of documented death;Timepoint(s) of evaluation of this end point: Date of documented death | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Survival rate is defined as the rate of patients alive at each time point • Overall Progression Free Survival (PFS) is defined as the delay between the date of randomization to the date of documented progression or any cause of death during the study. Progression will be assessed by CT scan according to RECIST criteria version 1.1 as defined in table 5. • PFS rate is defined as the rate of patients without progression or death at each time point • Overall Time To Progression (TTP) is defined as the time from the date of randomization to the date of documented progression defined according to RECIST criteria version 1.1 • TTP rate is defined as the rate of patients without documented progression at each time point • Best Response is defined as the best response (CR or PR or SD or PD) defined according to to RECIST criteria version 1.1 recorded from the start of the treatment until end of study. • Best Response rate is defined as the number of patients achieving the Best Response divided by the total number of patients in the population of analysis. • Objective response rate (CR + PR) is defined as the number of patients with documented partial response or complete response defined according to RECIST, divided by the number of randomized patients • Disease control rate (CR + PR + SD) is defined as the number of patients with documented partial response, complete response or stable disease defined according to RECIST criteria version 1.1, divided by the number of patients randomized at each time point. ;Timepoint(s) of evaluation of this end point: Every 8 weeks | — |
Countries
Argentina, Austria, Canada, China, Cyprus, Czech Republic, Egypt, France, Greece, Hong Kong, Hungary, India, Israel, Italy, Korea, Republic of, Lebanon, Malaysia, Mexico, Morocco, Myanmar, Peru, Philippines, Romania, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Spain, Taiwan, Tunisia, Ukraine, United Kingdom, United States
Contacts
Public ContactOlivier Eydoux
AB Science
Outcome results
None listed