A specially designed study conducted at many medical sites to compare whether Masitinib, in combination with a currently available medicine called Folfiri, to placebo in combination with Folfiri, is safe and effective in second line treatment of patients with advanced colorectal cancer.
- Conditions
- Metastatic colorectal cancerMedDRA version: 17.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-000490-79-GB
- Lead Sponsor
- AB Science
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 550
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 10EE9/L,
- Haemoglobin = 10 g/dl,
- Platelets (PLT) = 75 x 10EE9/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,
- Normal Creatinine or if abnormal creatinine, creatinine clearance = 50 mL/min (Cockcroft and Gault formula),
- Albumin > 1 x LLN,
- Proteinuria < 30 mg/dL (1+) on the dipstick. If proteinuria is = 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours;
8. Patient with life expectancy > 3 months;
9. Female or male patient = 18;
10. Patient weight >40 kg and BMI > 18;
11. Females of childbearing potential must have a negative serum beta human chorionic gonadotropin (ß-hCG) within seven days prior to the initiation of treatment. Females of childbearing potential must have used simultaneously two highly effective methods of contraception (strongly recommended that one of the two forms of contraception be non hormonal such as condom plus spermicide, condom plus diaphragm with spermicide, or have
a vasectomized partner) or use an intrauterine device or must have been sexually abstinent for at least four weeks prior to or at least one menstrual cycle prior to (whichever is longer) the
negative pregnancy test through entry the study and for 3 months after the last treatment intake. Sexual abstinence or effective contraception must be used for at least one month prior to the initiation of therapy, during therapy, and for at least three months following discontinuation of therapy. This protocol defines a female of childbearing potential as a sexually mature woman who has not undergone a hysterectomy or bilateral oophorectomy or has not been naturally postmenopausal for at least 24 consecutive months;
12. Male patients with female partners of childbearing potential must agree to sexual abstinence or to practice two reliable forms of effective contraception used simultaneously (strongly recommended that one of the two forms of contraception be non-hormonal such
as condom plus spermicide, condom plus diaphragm with spermicide, or partner with tubal ligation) or partner may use an intrauterine device, during the entire period of study treatment and for at least three months after treatment is discontinued;
13. Male patients with female sexual partners who are pregnant, possibly pregnant or who could become pregnant during the study must agree to use condoms during sexual intercourse during the entire period of study treatment and for at least three month after the last dose of study treatment;
14. Patient able and willing to comply with study procedures as per protocol;
15. Patient able to underst
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 enrolment, 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.
12. Patient receiving or requiring any prohibited medication (Section 6.3.2 of the Protocol).
WASH OUT
13. Any previous treatment with an investigational agent or chemotherapy or biological agent will require a wash-out period of four weeks prior to baseline.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): Overall Survival (OS);Timepoint(s) of evaluation of this end point: Defined as time from first randomisation to date of documented death.;Main Objective: To compare the overall survival (OS) defined as the time from the randomisation to the date of documented death, of masitinib at 6mg/Kg/day in combination with standard therapy FOLFIRI (irinotecan, 5-fluorouracil and folinic acid) to matching placebo in combination with standard therapy FOLFIRI in second line treatment of patients with metastatic colorectal cancer.;Secondary Objective: To compare the efficacy (Progression Free Survival), the safety and the quality of life of masitinib at 6mg/Kg/day in combination with standard therapy FOLFIRI (irinotecan, 5-fluorouracil and folinic acid) to matching placebo in combination with standard therapy FOLFIRI in second line treatment of patients with metastatic colorectal cancer.
- Secondary Outcome Measures
Name Time Method