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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Irinotecan; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Bevacizumab; Drug: Bevacizumab; Drug: Irinotecan; Drug: Capecitabine

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 330
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 72 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; FOLFIRI/Avastin	Drug: Irinotecan; Irinotecan 150mg/m2 IV on day 1 every 2 weeks for 10 cycles; Other Names: 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 Names: 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 Names: LV; Drug: Bevacizumab; Bevacizumab 5mg/kg IV on day 1 every 2 weeks for 10 cycles; Other Names: Avastin; Drug: Bevacizumab; Bevacizumab 7,5mg/kg IV on day 1 every 3 weeks for 6 cycles; Other Names: Avastin; Drug: Irinotecan; Irinotecan 250mg/m2 IV on day 1 every 3 weeks for 6 cycles; Other Names: CPT-11
Experimental: 2; XELIRI/Avastin	Drug: Irinotecan; Irinotecan 150mg/m2 IV on day 1 every 2 weeks for 10 cycles; Other Names: CPT-11; Drug: Bevacizumab; Bevacizumab 5mg/kg IV on day 1 every 2 weeks for 10 cycles; Other Names: Avastin; Drug: Bevacizumab; Bevacizumab 7,5mg/kg IV on day 1 every 3 weeks for 6 cycles; Other Names: Avastin; Drug: Irinotecan; Irinotecan 250mg/m2 IV on day 1 every 3 weeks for 6 cycles; Other Names: CPT-11; Drug: Capecitabine; Capecitabine 2000mg/m2 p.o. daily, for days 1-14, every 3 weeks for 6 cycles; Other Names: Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time To Progression	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity profile	Toxicity assessment on each chemotherapy cycle
Symptoms improvement	Assessment every two cycles
Quality of life	Assessment every two cycles
Overall Survival	Probability of 1-year survival (%)
Objective Response Rate	Objective responses confirmed by CT or MRI (on 3rd and 6th cycle)

Collaborators and Investigators

• Sponsor: Hellenic Oncology Research Group
• Collaborators: University Hospital of Crete
• Investigators: Principal Investigator: John Souglakos, MD, johnsougl@gmail.com

Publications and helpful links

General Publications

• Souglakos J, Ziras N, Kakolyris S, Boukovinas I, Kentepozidis N, Makrantonakis P, Xynogalos S, Christophyllakis Ch, Kouroussis Ch, Vamvakas L, Georgoulias V, Polyzos A. Randomised phase-II trial of CAPIRI (capecitabine, irinotecan) plus bevacizumab vs FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) plus bevacizumab as first-line treatment of patients with unresectable/metastatic colorectal cancer (mCRC). Br J Cancer. 2012 Jan 31;106(3):453-9. doi: 10.1038/bjc.2011.594. Epub 2012 Jan 12.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: May 3, 2007
• First Submitted That Met QC Criteria: May 3, 2007
• First Posted (Estimate): May 4, 2007

Study Record Updates

• Last Update Posted (Estimate): August 19, 2010
• Last Update Submitted That Met QC Criteria: August 18, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Capecitabine; Bevacizumab; Irinotecan; Metastatic colorectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Capecitabine; Bevacizumab; Leucovorin; Irinotecan
• Other Study ID Numbers: CT/05.16