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

Sponsors and Collaborators:	Hellenic Oncology Research Group University Hospital of Crete
Information provided by:	Hellenic Oncology Research Group
ClinicalTrials.gov Identifier:	NCT00469443

Purpose

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.

Condition	Intervention	Phase
Colorectal Cancer	Drug: Irinotecan Drug: 5-Fluorouracil Drug: Leucovorin Drug: Capecitabine Drug: Bevacizumab	Phase III

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Irinotecan U 101440E Irinotecan hydrochloride Capecitabine Bevacizumab Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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

Further study details as provided by Hellenic Oncology Research Group:

Primary Outcome Measures:

Time To Progression [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	330
Study Start Date:	December 2006
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

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

Arms

Assigned Interventions

1: Experimental

FOLFIRI/Avastin

Drug: Irinotecan

Irinotecan 150mg/m2 IV on day 1 every 2 weeks for 10 cycles

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

Drug: Leucovorin

Leucovorin 200 mg/m2 infused over 2 hours IV, on day 1 and 2 every 2 weeks for 10 cycles

Drug: Bevacizumab

Bevacizumab 5mg/kg IV on day 1 every 2 weeks for 10 cycles

2: Experimental

XELIRI/Avastin

Drug: Capecitabine

Capecitabine 2000mg/m2 p.o. daily, for days 1-14, every 3 weeks for 6 cycles

Drug: Bevacizumab

Bevacizumab 7,5mg/kg IV on day 1 every 3 weeks for 6 cycles

Drug: Irinotecan

Irinotecan 250mg/m2 IV on day 1 every 3 weeks for 6 cycles

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.

Eligibility

Ages Eligible for Study:	18 Years to 72 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00469443

Contacts

Contact: Dora Hatzidaki	+302810392570	dorachat@med.uoc.gr
Contact: Sofia Mavraki	+302810392987	maurakh@gmail.com

Locations

Greece
"Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology	Recruiting
Thessaloniki, Greece
Contact: George Tavoularis +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +302106457968 secretary@horg.gr
Principal Investigator: Ioannis Boukovinas, MD
"Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine	Recruiting
Athens, Greece
Contact: George Tavoularis +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +302106457968 secretary@horg.gr
Principal Investigator: Aris Polyzos, MD
"Metaxa's" Anticancer Hospital of Piraeus, 1st Dep of Medical Oncology	Recruiting
Piraeus, Greece
Contact: George Tavoularis +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +302106457968 secretary@horg.gr
Principal Investigator: Nikos Ziras, MD
"IASO" General Hospital of Athens, 1st Dep of Medical Oncology	Recruiting
Athens, Greece
Contact: George Tavoularis +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +302106457968 secretary@horg.gr
Principal Investigator: Stelios Giassas, MD
University General Hospital of Alexandroupolis, Dep of Medical Oncology	Recruiting
Alexandroupolis, Greece
Contact: George Tavoularis +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +302106457968 secretary@horg.gr
Principal Investigator: Stelios Kakolyris, MD
Air Forces Military Hospital of Athens	Recruiting
Athens, Greece
Contact: George Tavoularis +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +302106457968 secretary@horg.gr
Principal Investigator: Nikos Kentepozidis, MD
State General Hospital of Larissa	Recruiting
Larissa, Greece
Contact: George Tavoularis +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +302106457968 secretary@horg.gr
Principal Investigator: Athanasios Athanasiadis, MD
401 Military Hospital of Athens	Recruiting
Athens, Greece
Contact: George Tavoularis +302106448666 secretary@horg.gr
Contact: Spyros Georgiadis +302106457968 secretary@horg.gr
Principal Investigator: Charalampos Christophillakis, MD

Sponsors and Collaborators

Hellenic Oncology Research Group

University Hospital of Crete

Investigators

Principal Investigator:

John Souglakos, MD

johnsougl@gmail.com

More Information

No publications provided

Responsible Party:	Hellenic Oncology Research Group ( J.Sougklakos )
Study ID Numbers:	CT/05.16
Study First Received:	May 3, 2007
Last Updated:	January 29, 2009
ClinicalTrials.gov Identifier:	NCT00469443 History of Changes
Health Authority:	Greece: National Organization of Medicines

Keywords provided by Hellenic Oncology Research Group:

Metastatic colorectal cancer
Irinotecan
Capecitabine
Bevacizumab

Study placed in the following topic categories:

Antimetabolites
Capecitabine
Vitamin B Complex
Digestive System Neoplasms
Immunologic Factors
Gastrointestinal Diseases
Colonic Diseases
Irinotecan
Leucovorin
Trace Elements
Bevacizumab
Intestinal Diseases

Angiogenesis Inhibitors
Immunosuppressive Agents
Rectal Diseases
Intestinal Neoplasms
Digestive System Diseases
Vitamins
Fluorouracil
Gastrointestinal Neoplasms
Micronutrients
Antineoplastic Agents, Phytogenic
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Gastrointestinal Diseases
Antineoplastic Agents
Colonic Diseases
Irinotecan
Physiological Effects of Drugs
Leucovorin
Bevacizumab
Rectal Diseases
Neoplasms by Site
Vitamins
Therapeutic Uses

Growth Inhibitors
Angiogenesis Modulating Agents
Micronutrients
Capecitabine
Vitamin B Complex
Digestive System Neoplasms
Growth Substances
Enzyme Inhibitors
Intestinal Diseases
Angiogenesis Inhibitors
Immunosuppressive Agents
Intestinal Neoplasms
Pharmacologic Actions
Neoplasms
Digestive System Diseases

ClinicalTrials.gov processed this record on May 06, 2009