Clinical trial NCT00469443: Randomized Phase III Study of Folfiri+Avastin Versus Xeliri+Avastin as 1st Line Treatment of CRC
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: Metastatic colorectal cancer
Irinotecan
Capecitabine
Bevacizumab
Lead sponsor: Hellenic Oncology Research Group
Sponsor class: OTHER
Collaborators: name: University Hospital of Crete
First posted: 2007-05-04
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Time To Progression
timeFrame: 1 year
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Objective responses confirmed by CT or MRI (on 3rd and 6th cycle)
measure: Overall Survival
timeFrame: Probability of 1-year survival (%)
measure: Toxicity profile
timeFrame: Toxicity assessment on each chemotherapy cycle
measure: Quality of life
timeFrame: Assessment every two cycles
measure: Symptoms improvement
timeFrame: Assessment every two cycles
Other outcomes:
Locations:
city: Alexandroupolis
country: Greece
facility: University General Hospital of Alexandroupolis, Dep of Medical Oncology
city: Athens
country: Greece
facility: "IASO" General Hospital of Athens, 1st Dep of Medical Oncology
city: Athens
country: Greece
facility: "Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine
city: Athens
country: Greece
facility: 401 Military Hospital of Athens
city: Athens
country: Greece
facility: Air Forces Military Hospital of Athens
city: Larissa
country: Greece
facility: State General Hospital of Larissa
city: Piraeus
country: Greece
facility: "Metaxa's" Anticancer Hospital of Piraeus, 1st Dep of Medical Oncology
city: Thessaloniki
country: Greece
facility: "Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology
Study officials:
affiliation: johnsougl@gmail.com
name: John Souglakos, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.