Randomized Phase III Study of Folfiri+Avastin Versus Xeliri+Avastin as 1st Line Treatment of CRC

• Objective Response Rate [ Time Frame: Objective responses confirmed by CT or MRI (on 3rd and 6th cycle) ] [ Designated as safety issue: No ]
• Overall Survival [ Time Frame: Probability of 1-year survival (%) ] [ Designated as safety issue: No ]
• Toxicity profile [ Time Frame: Toxicity assessment on each chemotherapy cycle ] [ Designated as safety issue: Yes ]
• Quality of life [ Time Frame: Assessment every two cycles ] [ Designated as safety issue: No ]
• Symptoms improvement [ Time Frame: Assessment every two cycles ] [ Designated as safety issue: No ]

This phase III study will compare two combinations of irinotecan, Folfiri versus Xeliri, with the addition of Avastin as 1st line treatment of colorectal cancer.

There is no data of comparison for Folfiri and Xeliri regimens. The reported data demonstrated that the addition of Avastin in the combination of irinotecan/bolus 5-FU/LV has significant improvement of overall survival. Further analysis of these results showed that patients receiving irinotecan in combination with Avastin, as 1st line treatment and oxaliplatin with Avastin, as second line treatment, have median overall survival 25, 1 months, which is the longest survival that has been reported.

• Drug: Irinotecan
  Irinotecan 150mg/m2 IV on day 1 every 2 weeks for 10 cycles
  Other Name: CPT-11
• Drug: 5-Fluorouracil
  5-Fluorouracil 400 mg/m2 infused over 10 min IV and 5-FU 600 mg/m2 infused over 22 hours IV, on Day 1 and 2 (De Grammont regimen), every 2 weeks for 10 cycles
  Other Name: 5-FU
• Drug: Leucovorin
  Leucovorin 200 mg/m2 infused over 2 hours IV, on day 1 and 2 every 2 weeks for 10 cycles
  Other Name: LV
• Drug: Capecitabine
  Capecitabine 2000mg/m2 p.o. daily, for days 1-14, every 3 weeks for 6 cycles
  Other Name: Xeloda
• Drug: Bevacizumab
  Bevacizumab 5mg/kg IV on day 1 every 2 weeks for 10 cycles
  Other Name: Avastin
• Drug: Bevacizumab
  Bevacizumab 7,5mg/kg IV on day 1 every 3 weeks for 6 cycles
  Other Name: Avastin
• Drug: Irinotecan
  Irinotecan 250mg/m2 IV on day 1 every 3 weeks for 6 cycles
  Other Name: CPT-11

• Experimental: 1
  FOLFIRI/Avastin
  Interventions:

  • Drug: Irinotecan
  • Drug: 5-Fluorouracil
  • Drug: Leucovorin
  • Drug: Bevacizumab
• Experimental: 2
  XELIRI/Avastin
  Interventions:

  • Drug: Capecitabine
  • Drug: Bevacizumab
  • Drug: Irinotecan

Inclusion Criteria:

• Histologically confirmed locally advanced or metastatic colorectal cancer
• Measurable or evaluable disease
• ECOG performance status ≤ 2
• Age 18 - 72 years
• Adequate liver (Bilirubin ≤ 1.5 UNL, SGOT/SGPT ≤ 4 UNL, ALP ≤ 2.5 UNL), renal (Creatinine ≤ 1.5 UNL) and bone marrow (ANC ≥ 1,500/mm3, PLT ≥ 100,000/mm3) function
• Patients with history of hemoptysis or with increased risk of thromboembolic events should be observed carefully due to administration of Avastin
• Patients must be able to understand the nature of this study
• Written informed consent

Exclusion Criteria:

• Previous 1st line chemotherapy
• Adjuvant chemotherapy with Irinotecan regimen with relapse < 6 months after the completion
• Active infection
• History of serious cardiac disease (unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, ventricular arrhythmias)
• Previous radiotherapy within the last 4 weeks or > 25% of bone marrow
• Patients with unstable CNS metastases
• Patients with chronic diarrhea (at least for 3 months) or partial bowel obstruction
• Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer
• Psychiatric illness or social situation that would preclude study compliance
• Pregnant or lactating women
• Patients > 65 years with history of arterial thromboembolic, myocardial infarction, unstable angina and pulmonary embolism