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Trial registered on ANZCTR


Registration number
ACTRN12610000270011
Ethics application status
Approved
Date submitted
29/03/2010
Date registered
1/04/2010
Date last updated
11/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Randomized phase III trial of irinotecan in combination with capecitabine or fluorouracil (5-FU)/leucovorin (LV) and bevacizumab as first-line treatment in patients with metastatic colorectal cancer
Scientific title
Randomized phase III trial to compare progression free survival in patients with metastatic colorectal cancer receiving irinotecan in combination with capecitabine or fluorouracil (5-FU)/leucovorin (LV) and bevacizumab: (xeliri-bevacizumab vs folfiri-bevacizumab) as first-line treatment. A study of the Hellenic Cooperative Oncology Group (HeCOG)
Secondary ID [1] 1385 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic colorectal cancer 256784 0
Condition category
Condition code
Cancer 256931 256931 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Bevacizumab (AVASTIN): 7.5 mg/kg of body weight, 90min intravenous (i.v.) infusion day 1 (AVASTIN should not be mixed into Dextrose solutions)
followed by
Irinotecan (CPT-11): 240mg/m2 intravenous (i.v.), 90 minutes infusion day 1
followed by
Capecitabine (XELODA):1000 mg/m2 per os (it is administered orally within 30 minutes after the end of breakfast or dinner) twice daily days 1-14

The regimen will be repeated every 3 weeks for a total of 6 cycles. Treatment should be continued for 6 cycles and be interrupted in case of progression of disease during treatment or non-acceptable toxicity or consent withdrawal. After the end of treatment, patients are followed every 3 months until death or until the date of interruption (date of disease progression or initiation of other antineoplastic treatment).
Intervention code [1] 255988 0
Treatment: Drugs
Comparator / control treatment
Bevacizumab (AVASTIN): 5 mg/kg body weight, i.v. 90min infusion day 1
followed by
Irinotecan (CPT-11): 180mg/m2 i.v, 30-90 min infusion day 1
followed by
Leucovorin (LV): 200mg/m2 i.v, 2 hours infusion (concomitantly with irinotecan) day 1, 5-Fluorouracil (5-FU): 400 mg/m2 IV bolus day 1 followed by 5-FU 2400 mg/m2 46 hours continuous infusion.

The regimen will be repeated every 2 weeks for a total of 12 cycles
Control group
Active

Outcomes
Primary outcome [1] 257804 0
Progression Free Survival (PFS)
Timepoint [1] 257804 0
8 months from study initiation. This outcome is assessed by laboratory evaluation of hematology and biochemistry (including tumor markers), computed tomography (CT) scan or other imaging studies as indicated.
Secondary outcome [1] 263220 0
Safety of administration of each chemotherapeutic arm
Timepoint [1] 263220 0
1 month since the last administration of the drug. Toxicity is assessed by laboratory evaluation of hematology and biochemistry, physical examination etc.
Secondary outcome [2] 263221 0
Objective response rate (ORR)
Timepoint [2] 263221 0
The ORR will be assessed by imaging methods including computed tomography (CT) scan, bone scan, X-ray etc. They will be repeating after 3 cycles of XELIRI or 6 cycles of FOLFIRI, after the completion of chemotherapy and every 3 months thereafter until date of disease progression or consent withdrawal or death.
Secondary outcome [3] 263775 0
Overall Survival
Timepoint [3] 263775 0
5 years from study initiation

Eligibility
Key inclusion criteria
1.Histologically or cytologically documented locally advanced or metastatic colorectal cancer
2.Two-dimensional measurable disease at least at one site, not previously irradiated (newly emerged disease at previously irradiated sites is acceptable). Ascites and pleural fluid are not considered measurable disease.
3. The diameter of one measurable lesion should be (at least one dimension)>=15 mm
4. No previous administration of chemotherapy (only neoadjuvant or adjuvant chemotherapy completed at least 4 months before patient enrollment in the protocol is acceptable).
5. Time between other anticancer treatments and patient enrollment should be:>= 4 weeks for major surgical intervention · >= 4 weeks for radiotherapy
6. Age>=18 years and performance status ECOG (Eastern Cooperative Oncology Group) 0-2
7. Expected life span > 3 months
8. Written informed consent
9. Adequate bone marrow function:
Hemoglobin >= 10 gr/dL
White blood cell >= 4 x 10^9/ L
Neutrophils >= 2 x 10^9/ L
Platelets >= 100 x 10^9/ L
10. Adequate hepatic and renal function
Total bilirubin <= 1.5 x UNL
Serum glutamic oxaloacetic transaminase (SGOT) <= 2.5 x UNL
Serum glutamic pyruvic transaminase (SGPT)<= 2.5 x UNL
Alkaline phosphates <= 2.5 x UNL
Creatinine <= 1.5 x UNL
11. In case of liver metastases:
Total bilirubin <= 2.5 x UNL
Serum glutamic oxaloacetic transaminase (SGOT) <= 5.0 x UNL
Serum glutamic pyruvic transaminase (SGPT) <= 5.0 x UNL
Alkaline phosphatase <= 5.0 x UNL
12. In case of bone metastases:
Alkaline phosphatase <= 10.0 x UNL

UNL: Upper normal limit of approved normal values.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Malignant tumors other than colorectal adenocarcinoma
2.History of other malignant disease, excluding non-melanoma cancer of the skin and in-situ cervical cancer
3.Concomitant irradiation of a measurable lesion
4.Other concomitant anticancer treatment
5.Concomitant (or in the last 4 weeks before patient enrollment) administration of other investigational drugs
6.Measurable liver lesion affecting >50% of organ function
7.Other serious concomitant diseases or compromised general condition, including major neurological and psychiatric disorders 8.Severe cardiac disease (congestive heart failure, symptomatic coronary insufficiency, history of myocardial infarction in the last 6 months, uncontrolled high-risk arterial hypertension or uncontrolled cardiac arrhythmia)
9.Uncontrolled metabolic disorders (unstable diabetes mellitus or other contraindications to corticosteroids) or serious uncontrolled active infection
10.Brain metastases and patients with bone metastases or serosal effusions as the only sites of disease
11.Inflammatory bowel disease or loss of proximal gastrointestinal tract integrity or malabsorption syndrome
12.Complete or partial bowel obstruction
13. Current history of chronic diarrhea
14.The patient had a major surgical operation in the last 4 weeks before enrollment and has not recovered yet
15.Pregnant or breastfeeding women
16.Female fertile patients not using an appropriate form of contraception
17.Patients with allo-transplanted organs 18.Inadequate follow-up because of psychological, socioeconomic, or other factors.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 2471 0
Greece
State/province [1] 2471 0

Funding & Sponsors
Funding source category [1] 256491 0
Other Collaborative groups
Name [1] 256491 0
Hellenic Cooperative Oncology Group
Address [1] 256491 0
18, Hatzikostandi str, 11524, Athens
Country [1] 256491 0
Greece
Primary sponsor type
Other Collaborative groups
Name
Hellenic Cooperative Oncology Group
Address
18, Hatzikostandi str, 11524, Athens
Country
Greece
Secondary sponsor category [1] 255804 0
None
Name [1] 255804 0
Address [1] 255804 0
Country [1] 255804 0

Ethics approval
Ethics application status
Approved

Summary
Brief summary
This is a randomized phase III trial of irinotecan in combination with capecitabine or 5-Fluorouracil/Leucovorin and bevacizumab: (xeliri-bevacizumab vs folfiri-bevacizumab) as first-line treatment in patients with metastatic colorectal cancer. The primary objective of this study is to test the antineoplastic activity, expressed as progression-free survival, of XELIRI regimen vs FOLFIRI, in patients with metastatic colorectal cancer not previously treated for advanced disease. The secondary objectives are to evaluate the convenience and safety of the two regimens as well as to evaluate the response rate and the overall survival.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30818 0
Address 30818 0
Country 30818 0
Phone 30818 0
Fax 30818 0
Email 30818 0
Contact person for public queries
Name 14065 0
Eleni Papakostaki
Address 14065 0
Hellenic Cooperative Oncology Group, 18, Hatzikostandi str, 11524, Athens
Country 14065 0
Greece
Phone 14065 0
+302106912520
Fax 14065 0
+302106912713
Email 14065 0
hecogoff@otenet.gr
Contact person for scientific queries
Name 4993 0
Dimitrios Pectasides
Address 4993 0
Hellenic Cooperative Oncology Group, 18, Hatzikostandi str, 11524, Athens
Country 4993 0
Greece
Phone 4993 0
+302106912520
Fax 4993 0
+302106912713
Email 4993 0
pectasid@otenet.gr

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary