A Prospective Angiogenic Imaging Study With DCE-MRI and DCE-USI in Patients With Colorectal Cancer and Liver Metastases Receiving Sunitinib in Addition to 5-FU, Folinic Acid and Irinotecan (FOLFIRI) as 1st Line Therapy
- Adult males and females: over 18 years of age.
- Patients with histologically or cytologically confirmed colorectal cancer who will
receive their first palliative treatment.
- Patients who have at least one measurable hepatic lesion of 2 cm or more according to
- ECOG 0 or 1.
- Signed written informed consent.
- White blood cell count (WBC)>= 4x10^9/L with neutrophils >= 1.5 x 10*9/L, platelet
count >= 100x10*9/L, hemoglobin >= 5.6 mmol/L (10 g/dL).
- Total bilirubin =< 2 x upper limit of normal.
- AST and ALT =< 2.5 x upper limit of normal, or =< 5 x upper limit of normal in case
of liver metastases.
- Serum creatinine =< 1.5 x upper limit of normal or creatinine clearance > 60 ml/min
- Normal ECG without QT prolongation.
- Resectable liver metastasis.
- Adjuvant therapy with FOLFOX or 5-FU / Capecitabine =< 6 months prior to treatment on
study or any previous palliative chemotherapy..
- Any contraindication for FOLFIRI chemotherapy regimen.
- Any investigational drug within the 30 days before inclusion.
- Prior use of sunitinib or other multitarget tyrosine kinase inhibitors or VEGF
pathway directed treatments like bevacizumab.
- Known or suspected allergy or hypersensitivity reaction to any of the components of
- Pregnancy (absence to be confirmed by beta-hCG test) or lactation period
- Men or women of child-bearing potential who are sexually active and unwilling to use
a medically acceptable method of contraception during the trial
- Clinically symptomatic brain or meningeal metastasis. (known or suspected)
- Cardiac arrhythmias requiring anti-arhythmics (excluding beta blockers or digoxin).
- History of any of the following cardiac events within the past 6 months:
- myocardial infarction (including severe/ unstable angina),
- coronary/peripheral artery bypass graft,
- congestive heart failure (CHF),
- cerebrovascular accident,
- transient ischemic attack pulmonary embolism.
- History of clinically significant bleeding within the past 6 months, including gross
hemoptysis or haematuria, or underlying coagulopathy.
- History of peptic ulcer disease, deep vein thrombosis, or other significant
thrombo-embolic event within the past 6 months.
- Uncontrolled severe hypertension (failure of diastolic blood pressure to fall below
90 mm Hg despite the use of >= 3 anti-hypertensive drugs.
- Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease or
- Previous malignancy (other than colorectal cancer) in the last 5 years except basal
cell cancer of the skin, pre-invasive cancer of the cervix or superficial bladder
tumor [Ta, Tis and T1].
- History of organ allograft
- Treatment with potent CYP3A4 inhibitor within 7 days of sunitinib/placebo dosing or
with potent CYP3A4 inducer within 12 days of sunitinib/placebo dosing.
- Prior full field radiotherapy =< 4 weeks, or limited field radiotherapy, =< to 2
weeks prior to study enrollment; or previous radiation treatment >30% of the bone
- Major surgical procedure, open biopsy or significant traumatic injury within 4 weeks
before starting treatment; anticipation of need for major surgical procedure (e.g.
impending bowel obstruction) during the course of the study.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to study enrollment, unless affected area has been
- Significant disease which, in the investigator's opinion would exclude the patient
from the study.
- Patients with seizure and epileptic disorder or other conditions requiring medication
such as phenytoin, carbamazepin, phenobarbital.
- Patients requiring long-term cortisone therapy.
- Patients requiring oral anticoagulation treatment (marcoumar).
- Known alcohol or drug abuse.
- Medical or psychological conditions that would not permit the patient to complete the
study or sign informed consent.