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

Colorectal Cancer Clinical Trial

Official title:

A Randomized Phase III Study of Irinotecan Plus 5-fluorouracil Plus Leucovorin and Bevacizumab (FOLFIRI+Avastin) Versus Irinotecan Plus Capecitabine and Bevacizumab (XELIRI+Avastin) as 1st Line Treatment of Locally Advanced or Metastatic Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00469443
• Other study ID #: CT/05.16
• Status: Completed
• Phase: Phase 3
• First received: May 3, 2007
• Last updated: August 18, 2010
• Start date: December 2006
• Est. completion date: February 2010

Study information

• Verified date: August 2010
• Source: Hellenic Oncology Research Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Greece: National Organization of Medicines
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 72 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Irinotecan
Irinotecan 150mg/m2 IV on day 1 every 2 weeks for 10 cycles
• 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
• Leucovorin
Leucovorin 200 mg/m2 infused over 2 hours IV, on day 1 and 2 every 2 weeks for 10 cycles
• Capecitabine
Capecitabine 2000mg/m2 p.o. daily, for days 1-14, every 3 weeks for 6 cycles
• Bevacizumab
Bevacizumab 5mg/kg IV on day 1 every 2 weeks for 10 cycles
• Bevacizumab
Bevacizumab 7,5mg/kg IV on day 1 every 3 weeks for 6 cycles
• Irinotecan
Irinotecan 250mg/m2 IV on day 1 every 3 weeks for 6 cycles

Locations

Country	Name	City	State
Greece	University General Hospital of Alexandroupolis, Dep of Medical Oncology	Alexandroupolis
Greece	"IASO" General Hospital of Athens, 1st Dep of Medical Oncology	Athens
Greece	"Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine	Athens
Greece	401 Military Hospital of Athens	Athens
Greece	Air Forces Military Hospital of Athens	Athens
Greece	State General Hospital of Larissa	Larissa
Greece	"Metaxa's" Anticancer Hospital of Piraeus, 1st Dep of Medical Oncology	Piraeus
Greece	"Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology	Thessaloniki

Sponsors (2)

Lead Sponsor	Collaborator
Hellenic Oncology Research Group	University Hospital of Crete

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time To Progression		1 year	No
Secondary	Objective Response Rate		Objective responses confirmed by CT or MRI (on 3rd and 6th cycle)	No
Secondary	Overall Survival		Probability of 1-year survival (%)	No
Secondary	Toxicity profile		Toxicity assessment on each chemotherapy cycle	Yes
Secondary	Quality of life		Assessment every two cycles	No
Secondary	Symptoms improvement		Assessment every two cycles	No