FOLFIRI and Sunitinib in Metastatic Colorectal Cancer

Inclusion Criteria:

• 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 RECIST criteria.
• 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.

Exclusion Criteria:

• 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 study treatments.
• 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 chronic diarrhea.
• 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 marrow.
• 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 removed surgically.
• 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.