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Trial registered on ANZCTR


Registration number
ACTRN12609000585224
Ethics application status
Approved
Date submitted
9/07/2009
Date registered
15/07/2009
Date last updated
6/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Chemotherapy with Camptothecin-11 (CPT-11), Fluorouracil (5FU), folinic acid and oxaliplatin in patients with metastatic colorectal cancer
Scientific title
A randomised phase II trial comparing the effect of Camptothecin-11 (CPT-11), Fluorouracil (5FU) and Folinic Acid versus CPT-11, 5FU and Folinic Acid followed by Oxaliplatin, 5FU and Folinic Acid on objective response rate in patients with metastatic colorectal cancer
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 237209 0
Condition category
Condition code
Cancer 237472 237472 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
CPT-11+ Folinic Acid+ 5FU weekly for 6 weeks on days 1,8,15,22,29 and 36 (followed by 2 weeks rest for a total cycle duration of 8 weeks) at the following doses:
CPT-11: 80 mg/m2 in 250 ml normal saline intravenous injection (IV) over 90 minutes
Folinic acid: 200 mg/m2 in 500 ml normal saline IV over 2 hours
5FU: 450 mg/m2 IV bolus.

This 8-week cycle will be administered in an identical manner again (i.e. total 16 weeks).

Then, it will be followed by Oxaliplatin+ Folinic Acid+ 5FU weekly for 6 weeks on days 1,8,15,22,29 and 36 (followed by 2 weeks rest for a total cycle duration of 8 weeks) at the following doses:
Oxaliplatin: 45 mg/m2 IV over a 90 min infusion
Folinic acid: 200 mg/m2 in 500 ml normal saline IV over 2 hours
5FU: 450 mg/m2 IV bolus

This 8-week cycle will be administered in an identical manner again (i.e. total 16 weeks).

The overall duration of the intervention will be 32 weeks in total (4 cycles).
Intervention code [1] 236906 0
Treatment: Drugs
Comparator / control treatment
CPT-11+Folinic Acid+5FU weekly for 6 weeks on days 1,8,15,22,29 and 36 (followed by 2 weeks rest for a total cycle duration of 8 weeks) at the following doses:
CPT-11: 80 mg/m2 in 250 ml normal saline intravenous injection (IV) over 90 minutes
Folinic acid: 200 mg/m2 in 500 ml normal saline IV over 2 hours
5FU: 450 mg/m2 IV bolus.

Folinic acid and 5FU will be given immediately after completion of CPT-11 infusion. Each course should be repeated every week for 6 weeks followed by a two week rest period. One cycle represents 6 infusions (8 weeks).

4 cycles in total will be undertaken over a duration of 32 weeks.
Control group
Active

Outcomes
Primary outcome [1] 238335 0
Objective Response Rate (ORR).
The ORR will be assessed by imaging methods including computed tomography (CT) scan, bone scan, X-ray etc.
Timepoint [1] 238335 0
At 32 months from study initiation
Secondary outcome [1] 244765 0
Overall survival.
Timepoint [1] 244765 0
5 years from study initiation
Secondary outcome [2] 244766 0
Toxicity profile of both arms
Timepoint [2] 244766 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 [3] 244792 0
Progression free survival
Timepoint [3] 244792 0
5 years from study initiation

Eligibility
Key inclusion criteria
INCUSION CRITERIA
Histologically confirmed metastatic adeno-carcinoma of the colon or rectum.
Measurable metastatic disease (at least one) bidimensionally measurable lesion [according to WHO (World Health Organization) criteria].
No potentailly resectable metastasis.
Patients should be over 18 years old.
WHO/ECOG (Eastern Cooperative Oncology Group) performance status 0-2.
No prior chemotherapy or only adjuvant chemotherapy ended more than 6 months before randomisation.
Adequate renal and liver function creatinine <= 1.5 x upper normal limits, Serum glutamic oxaloacetic transaminase (SGOT)/Serum glutamic pyruvic transaminase (SGPT) <=5 x upper normal limits).
Baseline neutrophil count > 1,500/iL and platelet count > 100,000/iL.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
EXCLUSION CRITERIA
Pregnant or lactating patients.
Patients with reproductive potential who are not using adequate contraceptive measures.
Any prior chemotherapy for advanced disease. Adjuvant treatment ended within 6 months preceding study entry.
Central Nervous System (CNS) metastases, bone metastases or serosal effusions as the sole indicate of tumour.
Current history of chronic diarrhea.
Past or concurrent history of neoplasm other than colorectal adenocarcinoma, except for curatively treated non melanoma skin cancer or in situ carcinoma of the cervix.
Other serious illness (recent history of myocardial infarction, < 6 months).

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 2
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] 1866 0
Greece
State/province [1] 1866 0

Funding & Sponsors
Funding source category [1] 237304 0
Other Collaborative groups
Name [1] 237304 0
Hellenic Cooperative Oncology Group (HeCOG)
Address [1] 237304 0
18, Hatzikostandi str, 11524, Athens
Country [1] 237304 0
Greece
Primary sponsor type
Other Collaborative groups
Name
Hellenic Cooperative Oncology Group (HeCOG)
Address
18, Hatzikostandi str, 11524, Athens
Country
Greece
Secondary sponsor category [1] 236789 0
None
Name [1] 236789 0
Address [1] 236789 0
Country [1] 236789 0

Ethics approval
Ethics application status
Approved

Summary
Brief summary
The aim of this study was to compare the response rate (RR), progression free survival (PFS) and overall survival (OS) and to assess the toxicity profile of previously untreated patients with advanced colorectal cancer (CRC) randomly assigned between Camptothecin-11 (CPT-11)/5FU /Folinic Acid (arm A) versus Camptothecin-11 (CPT-11)/Fluorouracil (5FU)/Folinic Acid followed by Oxaliplatin/Fluorouracil (5FU)/Folinic Acid(arm B) in the same line of treatment.
A theoretical framework supports the hypothesis that the sequential administration of cytotoxic drugs at adequate doses can maximize the cell kill and overcome drug resistance.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29827 0
Address 29827 0
Country 29827 0
Phone 29827 0
Fax 29827 0
Email 29827 0
Contact person for public queries
Name 13074 0
Eleni Papakostaki
Address 13074 0
18, Hatzikostandi str, 11524, Athens
Country 13074 0
Greece
Phone 13074 0
+30 210 6912520
Fax 13074 0
Email 13074 0
hecogoff@otenet.gr
Contact person for scientific queries
Name 4002 0
Haralabos P. Kalofonos
Address 4002 0
Division of Oncology, Department of Medicine, University Hospital of Patras, 26500, Patras
Country 4002 0
Greece
Phone 4002 0
+30 2610 999535
Fax 4002 0
Email 4002 0
kalofon@med.upatras.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