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Trial registered on ANZCTR


Registration number
ACTRN12610000509066
Ethics application status
Approved
Date submitted
28/05/2010
Date registered
21/06/2010
Date last updated
23/03/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
A phase III clinical trial comparing the combination of capecitabine and oxaliplatin (XELOX) versus the combination of fluorouracil (5FU)/leucovorin (LV) and oxaliplatin (FOLFOX) as an adjuvant therapy in patients with operated colorectal cancer of stages B2 (high risk) and C (according to Duke's)
Scientific title
A phase III clinical trial comparing disease free survival between the combination of capecitabine and oxaliplatin (XELOX) versus the combination of fluorouracil (5FU)/leucovorin (LV) and oxaliplatin (FOLFOX) as an adjuvant therapy in patients with operated colorectal cancer of stages B2 (high risk) and C (according to Duke's)
Secondary ID [1] 251725 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
colorectal cancer 257273 0
Condition category
Condition code
Cancer 257421 257421 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
(XELOX) Xeloda: 1000 mg/m2 twice daily [by mouth (p.o.), morning and evening within 30 min of last meal], days 1 to 14 Oxaliplatin: 130 mg/m2 by 2-hour intravenous (IV) infusion, day 1

The treatment will commence in 4-6 weeks after surgery. Repeat every 21 days for 8 cycles
Intervention code [1] 256480 0
Treatment: Drugs
Comparator / control treatment
Leucovorin 200miligrams (mg)/m2 by 2-hour intravenous (IV) infusion, followed by IV bolus infusion 5-fluorouracil (5FU) 400 mg/m2 and then 46-hour 5FU infusion 2400mg/m2

The treatment will commence in 4-6 weeks after surgery. Repeat every 14 days for 12 cycles
Control group
Active

Outcomes
Primary outcome [1] 258434 0
To compare the 3-year DFS (disease free survival) between the two group therapies [Xeloda and Oxaliplatin (XELOX) versus 5-FU/Leucovorin and Oxaliplatin (FOLFOX)] in patients with colorectal cancer of stage B2 (high risk) and C, according to Dukes
Timepoint [1] 258434 0
Disease-free survival will be assessed in each patient by history and physical examination at each cycle and by history, physical examination, serum tumor markers [Carcinoembryonic Antigen (CEA), Carbohydrate Antigen 19-9 (CA19-9)], computed tomography of the abdomen and pelvis and chest x-rays every 4 months and endoscopy every 1 year during follow-up. The final outcome will be assessed 3 years after the enrollment of the last patient at the study.
Secondary outcome [1] 264214 0
Overall survival (OS)
Timepoint [1] 264214 0
This outcome is assessed 3 years after the enrollment of the last patient at the study. It is assessed using clinical data records
Secondary outcome [2] 264215 0
Cost comparison of treatment between the two arms
Timepoint [2] 264215 0
The length of hospital stays, the cost of the study drugs and other supportive medications and measures required to treat therapy and disease complications, the cost of laboratory, radiologic and other examinations and the length of stay off work because of treatment or disease complications will be assessed for each patient. Cost analysis will be performed at 3 years after the enrollment of the last patient at the study.
Secondary outcome [3] 264216 0
Evaluation of quality of life (QoL) in both arms of the trial
Timepoint [3] 264216 0
This outcome will be assessed using Euro-QoL 5D (EQ5D) questionnaires that each patient fills in at the beginning, at the end and 6 months after the completion of treatment.
Secondary outcome [4] 264217 0
Translational research
Timepoint [4] 264217 0
This outcome will be assessed using blood samples collected at the start of chemotherapy and formalin-fixed paraffin-embedded tumor tissue taken during surgery

Eligibility
Key inclusion criteria
1. Signed written informed consent on the trial relevant procedures
2. Histologically confirmed colon adenocarcinoma according to the International Organization Against Cancer (UICC) classification. The tumor must be radically excised. The patients must be histologically in a B2 (high risk) or C stage according to Duke’s. Stage B2 high risk includes: patients with poorly differenciated or mucous tumors, stage T4 tumors, outer-wall vein invasion, obstruction or perforation
3. During surgery at least eight (8) regional lymph nodes should be obtained
4. Absence of any metastatic or residual disease after surgery
5. Enrollment after 4 to 6 weeks after surgery
6. Age of >18 and <75 years
7. Performance status (according to Eastern Cooperative Oncology Group) <2
8. Satisfactory hematological profile, liver and renal function (within 14 days before the beginning of chemotherapy) that are described as follows:
- Hematological profile:
i. Neutrophils > 2.0x10^9 /L
ii. Platelets > 150x10^9 /L
iii.Hemoglobin > 10 g/dL
- Liver function tests:
i. Total bilirubin up to the upper normal limit
ii. Serum aspartate aminotransferase (AST) and Serum alanine aminotransferase (ALT) up to 2.5 times the upper normal limit
iii. Alkaline phosphatase up to 2.5 times the upper normal limit
- Renal function tests:
i. Creatinine up to 1.5 times the upper normal limitii. If the creatinine value is higher, the estimated creatinine clearance should be higher than 60 ml/hour
9.Negative pregnancy test (for women of reproductive age)
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with simultaneous metastasis from the primary tumor that has been totally excised
2. Concomitant therapy with other investigational products 3. Patients that have received previous anticancer therapy 4. Patients that cannot be monitored adequately due to psychological, social, geographic, economic or family reasons
5. Patients who clearly state that they want to enroll in a particular arm of the trial
6. Simultaneous serious disease that affects the participation in the trial
7. Psychiatric or other disorders that do not permit obtaining the informed consent and compliance of the patient to the schedule of the evaluation visits
8. Patients of reproductive age who refuse to take adequate contraceptive measures during the therapy
9. Prior or current history of: chronic diarrhea, inflammatory bowel disease, active peptic ulcer or intestinal bleeding
10. Hypersensitivity to oxaliplatin, capecitabine or to fluoropyrimidines
11. Recent history (last 6 months) of cardiac infarction, coronary disease, serious congestive heart failure, uncontrolled hypertension, non-controlled arrythmias
12. History of other neoplasm with the exception of in situ cervical carcinoma or non-melanoma skin cancer

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] 2608 0
Greece
State/province [1] 2608 0

Funding & Sponsors
Funding source category [1] 256970 0
Other Collaborative groups
Name [1] 256970 0
Hellenic Cooperative Oncology Group
Address [1] 256970 0
18, Hatzikostandi str, 11524, Athens
Country [1] 256970 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] 256350 0
None
Name [1] 256350 0
Address [1] 256350 0
Country [1] 256350 0

Ethics approval
Ethics application status
Approved

Summary
Brief summary
This is a phase III clinical trial comparing the combination of capecitabine and oxaliplatin (XELOX) versus the combination of 5-FU/LV and oxaliplatin (FOLFOX) as an adjuvant therapy in patients with operated colorectal cancer of stages B2 (high risk) and C. The primary endpoint is to compare the 3-year DFS (disease free survival) between the two group therapies
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31114 0
Address 31114 0
Country 31114 0
Phone 31114 0
Fax 31114 0
Email 31114 0
Contact person for public queries
Name 14361 0
Helen Papakostaki
Address 14361 0
Hellenic Cooperative Oncology Group, 18 Hatzikostandi str, 11524 Athens
Country 14361 0
Greece
Phone 14361 0
+30 1 2106912520
Fax 14361 0
+30 1 2106912713
Email 14361 0
hecogoff@otenet.gr
Contact person for scientific queries
Name 5289 0
Dimitrios Pectasides
Address 5289 0
Hellenic Cooperative Oncology Group, 18 Hatzikostandi str, 11524 Athens
Country 5289 0
Greece
Phone 5289 0
+30 1 2106912520
Fax 5289 0
+30 1 2106912713
Email 5289 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