Open – label, non randomized clinical study of Neoadjuvant chemotherapy with FOLFIRI and Avastin in patients with non-resectable liver metastases of colorectal cancer - Neoadjuvant chemotherapy with Bevacizumab

• Conditions: Metastatic (liver metastases) colorectal cancer, with no prior chemotherapy.; MedDRA version: 9.1Level: LLTClassification code 10024700Term: Liver metastases; MedDRA version: 9.1Level: LLTClassification code 10052358Term: Colorectal cancer metastatic

• Registration Number: EUCTR2007-002105-44-BG
• Lead Sponsor: Military Medical Academy Hospital for Active Treatment, Sofia

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-06-26
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Signed informed consent form prior to beginning specific protocol procedures showing the patients’ willingness and awareness to participate in the trial and comply with procedures

2. Age > 18 years

3. Patients with hystologically confirmed adenocarcinoma of the colon or the rectum.

4. Patients with colorectal cancer with nonresectable liver metastasis with resected or non resected primary tumor and lack of intestinal obstructions. Nonresectability is defined as:
a. Engagement of the hepatic parenchyma more than 6 segments.
b. Location of the lesions - near to large intrahepatic vessels – the two hepatic veins, vena cava,, lymphatic structures of the hepato-duodenal ligament and engagement of lymph nodes of truncus celiacus.

5. Six months progression free interval for patients who have been treated in adjuvant setting.

6. Patients with at least one target lesion, measured with CT scan < 4 weeks before the entrance in the study.

7. Patients with nonresectable extrahepatic disease.

8. ECOG = 2

9. Patients with no prior chemotherapy of the advanced disease.

10. End of radiotherapy 2 weeks prior to entry into the study

11. Adequate bone – marrow function – (leucocytes > 3 x 10 9/L, thrombocytes > 100 x 10 9/L, Hg >10g/dl and normal hemostasis).

12. Adequate hepatic (bilirubine <1.5 UNL, ALAT and ASAT < 5 UNL) renal (serum creatinine < 1.5 UNL and creatinine clearance >60/min Cockroft Goult) function.

13. Negative pregnancy test for the women with childbearing potential.

14. Life expectancy more than 3 months.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Patients with widespread metastatic disease as peritoneal metastases, multiple lung, bone or CNS metastases.

2. Patients with primary resectable liver metastases

3. Patients with hepatic insufficiency or severe hepatic disease (Child B and C) and clinically significant renal disease.

4. Patients with clinically significant heart disease (unstable angina pectoris, myocardial infarction, medicinally uncontrolled arterial hypertension, heart failure grade II or higher classified by NYHA, arrhythmia that needs medicinal treatment.

5. Patients with systemic anticoagulant therapy. Prophylactic anticoagulation for venous access devices is allowed provided the activity of the agent does not change INR or PTT measurements.

6. Use of aspirin on a regular basis at dose higher than 325 mg/day within 10 days prior to entry into the study

7. Serious, non-healing wound, ulcer, or bone fracture

8. Patients with serious infections – uncontrolled or that will need treatment.

9. Patients with severe CNS disorders – recent cerebro-vasular incident, epilepsy and psychiatric disorders.

10. Patient with uncontrolled diabetes.

11. Patient with another malignant disease in the last 5 years, excluding basocellular carcinoma of the skin or carcinoma in situ of the cervix.

12. Participation in another clinical study.

13. Men or women with childbearing potential who refuse to use effective contraception

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Assessment of the efficacy of the combination of Bevacizumab with irinotecan- based chemotherapy (FOLFIRI) or oral capecitabine (XELIRI) in terms of resectability of the primary non-resectable liver metastases from metastatic colorectal cancer. ;Secondary Objective: Assessment of disease free and overall survival of the patients who have undergone surgery for the metastases; <br>Assessment of the overall and hepatic toxicity of the treatment;<br>Peri- and postoperative complications and the quality of life of the patients; <br>Assessment of the serum and tumor levels of the fibroblastic and hepatocyte growth factors, response and resectability of the liver metastases and survival. <br>;Primary end point(s): Assessment of effect of neoadjuvant combination of FOLFIRI or XELIRI chemotherapy regimen and bevacizumab on the resectability of liver metastases initially assessed as unresectable.