A Phase Ⅱ Open Label, Non Randomized Study, in Which Sorafenib is Used in Combination With Irinotecan, Leucovorin and Fluorouracil in Patients With Advanced Colorectal Cancer After Failure of Oxaliplatin Treatment
1. Provision of written informed consent
2. Histological or cytological confirmed adenocarcinoma of the colon or rectum
3. Age between 18 and 75 years.
4. Patient with metastatic disease failed after at least 2 cycles of oxaliplatin-based
systemic chemotherapy, excluding adjuvant chemotherapy. Disease progression should be
proven by radiological evidence. A duration of 28 days after oxaliplatin therapy is
5. ECOG Performance Status of 0 or1
6. Life expectancy of at least 12 weeks
7. The required evidence of measurable lesions should be at least 10 mm in the longest
diameter by spiral computed tomography scan or 20 mm with conventional techniques
8. Adequate bone marrow, liver and renal function as assessed by the following
laboratory requirements to be conducted within 7 days prior to screening:
- Hemoglobin > 9.0 g/dl
- Absolute neutrophil count (ANC) >1,500/mm3
- Platelet count 100,000/μl
- Total bilirubin < 1.5 times the upper limit of normal ALT and AST < 2.5 x ULN(<
5 x ULN for patients with liver involvement of their cancer)
- ALP< 4 x ULN
- PT-INR/PTT < 1.5 x upper limit of normal
- Serum creatinine < 1.5 x ULN
1. Patients unable to swallow oral medications
2. History of cardiac disease:
- congestive heart failure >NYHA class 2
- active CAD (MI more than 6 mo prior to study entry is allowed)
- cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin
are permitted) or uncontrolled hypertension
3. History of HIV infection or chronic hepatitis B or C (high copy number of HBV).
4. Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
5. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months
from definitive therapy, has a negative imaging study within 4 weeks of study entry
and is clinically stable with respect to the tumor at the time of study entry)
6. Patients with seizure disorder requiring medication (such as steroids or
7. History of organ allograft ,The organ allograft may be allowed as protocol specific.
8. Patients undergoing renal dialysis
9. Previous or concurrent cancer that is distinct in primary site or histology from the
cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal
cell carcinoma within 5 years.
10. Patients with evidence or history of bleeding diathesis.Significant haemorrhage (>30
ml/bleeding episode in previous 3 months),haemoptysis (>5 ml fresh blood in previous
4 weeks) or thrombotic event (including transient ischaemic attack) in the previous
11. chronic inflammatory bowel disease; ileus; genetic fructose intolerance
12. Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results.
13. Any condition that is unstable or could jeopardize the safety of the patient and
their compliance in the study
14. Pregnant or breast-feeding patients. Women of childbearing potential must have a
negative pregnancy test performed within 7 days of the start of treatment. Both men
and women enrolled in this trial must use adequate barrier birth control measures
during the course of the trial (and men for at least 3 months after last
administration of study medication).
15. Prior exposure to the study drug.