Irinotecan, Capecitabine and Bevacizumab in Metastatic Colorectal Cancer Patients

Phase II Study of Irinotecan, Capecitabine and Bevacizumab in Metastatic Colorectal Cancer Patients

The purpose of this study is to determine efficacy and safety of the biweekly scheme with Capecitabine and Irinotecan, plus bevacizumab in patients with metastatic colorectal cancer.

The purpose of this study is to determine efficacy and safety of the biweekly scheme with Capecitabine and Irinotecan, plus bevacizumab in patients with metastatic colorectal cancer.

• Capecitabine: 1000 mg/m2, bid, oral, days 2-8. Every 2 weeks
• Irinotecan: 175 mg/m2, iv infusion 90 minutes, day 1, every 2 weeks
• Bevacizumab: 5 mg/kg day 1, every 2 Weeks

Inclusion Criteria:

1. Age > 18 years old (men and women)
2. ECOG Performance Status ≤ 2.
3. Histologically confirmed colorectal adenocarcinoma, metastatic disease.
4. No surgery option
5. No previous chemotherapy, except adjuvant treatment finished at least 6 months before the study inclusion
6. Have at least one measurable lesion according to the RECIST criteria
7. At least a 3-month life expectancy.
8. Written informed consent given.

Exclusion Criteria:

1. Patients who have previously received systemic treatment (for example, cytostatic chemotherapy or active/passive immunotherapy) for advanced or metastatic disease.

2. Patients previously treated with bevacizumab

3. Prior adjuvant or neoadjuvant treatment for non-metastatic disease (M0) is allowed, as long as it has concluded at least 6 months before beginning the treatment of the study.

4. If adjuvant treatment has previously been administered, the patients cannot have shown progression of the disease during treatment nor during the 6 months following termination thereof.

5. Prior radiotherapy is allowed if it has not been administered in the target lesions selected for this study, unless progression of said lesions in the irradiated field is documented, and as long as treatment has concluded at least 4 weeks before beginning the study.

6. Prior surgical treatment of the disease in stage IV is allowed.

7. Only non evaluable disease (non measurable) as ascitis, pleural effusion, diffuse hepatic, osseous metastasis

8. History of another neoplastic disease during the last five years, with the exception of cured basal cell carcinoma of the skin and cervical carcinoma in situ.

9. History or indications of CNS disease (for example, primary brain tumor, uncontrolled convulsions with standard medical treatment, cerebral metastases of any type or history of ictus) in the physical examination.

10. Medication or peripheral vascular disease, grade II or higher. Furthermore, those patients who have had a myocardial infarction in the year prior to beginning the treatment of the study will be excluded.

11. History of psychiatric disability that the investigator considers clinically significant, which prevents the patient from granting the informed consent or interferes with compliance of taking the oral medication

12. Clinically significant cardiovascular disease (i.e., active), for example, uncontrolled hypertension, unstable angina, congestive heart failure, class II or higher of the New York Heart Association (NYHA), severe cardiac arrhythmia

13. Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome or inability to take oral medication.

14. Patients subjected to organ allografts who require immunosuppressive treatment.

15. Severe, non-cicatrized osseous fractures, wounds or ulcers.

16. Indications of hemorrhagic diathesis or coagulopathy.

17. Severe, uncontrolled intercurrent infections or other severe, uncontrolled concomitant diseases.

18. Moderate or severe renal failure [creatinine clearance lower than 30 ml/min (calculated according to the Cockcroft-Gault Formula)] or serum creatinine > 1.5 x upper limit of normal (ULN).

19. Any of the following laboratory values:

    • Absolute neutrophils count (ANC) ≤ 1.5 x 109/l.
    • Platelet count ≤ 100 x 109/l.
    • Hemoglobin ≤ 9 g/dl.
    • INR > 1.5.
    • Total bilirubin >1.5 ULN.
    • ALS and/or AST > 2.5 x ULN or > 5 x ULN (in case of hepatic metastasis).
    • Alkaline phosphatase > 2.5 x ULN or 5 x ULN (in case of hepatic metastasis), or > 10 x ULN (in case of bone metastasis).

20. History of unexpected serious adverse events to fluoropyrimidine treatments or known dihidropyrimidine dehydrogenase (DPD) deficiency.

21. Patients subjected to major surgical procedure, open biopsy or patients have been significant traumatic injures in 28 days time before the initial study treatment, or patients with a major surgery procedure planning during the study period. Fine needle aspiration biopsy 7 days before the initial study.

22. Use of full dose of oral or parenteral anticoagulants ( at least 10 days before the initial study treatment or thrombolytic agents. Low dose of warfarin is allowed, with an INR ≤ 1.5

23. Subject requiring chronic use of high dose aspirin (> 325 m/day) or non-steroidal anti-inflammatory treatment (those known to inhibit platelet function at doses used to treat chronic inflammatory diseases).

24. Pregnant (serum positive pregnancy test) or lactating women.

25. Received any investigational drug or agent/ procedure, i.e. participation in another treatment trial within 30 days of randomisation.