Ignite Creation Date:
2024-05-05 @ 4:47 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00312000
Status:
COMPLETED
Last Update Posted:
2008-09-08
First Post:
2006-04-05
Brief Title:
Sequential Versus Combination Chemotherapy in Advanced Colorectal Carcinoma
Sponsor:
Dutch Colorectal Cancer Group
Organization:
Dutch Colorectal Cancer Group
Study Overview
Official Title:
A Randomised Study of Sequential Versus Combination Chemotherapy in Patients With Previously Untreated Advanced Colorectal Carcinoma
Status:
COMPLETED
Status Verified Date:
2008-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Primary objectiveTo assess the efficacy defined as overall survival of sequential versus combination chemotherapy for advanced colorectal cancer CRC
Methodology Open randomised multicenter phase III study Randomisation by centre will be centralized 820 patiënts with histologically proven advanced CRC not amenable to curative surgery Measurable or evaluable disease Age 18 years and above WHO performance status 0-2
Test products
Arm A First line capecitabine capecitabine 1250 mgm2 orally bid on day 1-14 q3until progression or unacceptable toxicity Second line irinotecan 350 mgm2 IV infusion on day 1 q3until progression or unacceptable toxicity Third line oxaliplatin 130 mgm2 IV infusion on day 1 and capecitabine 1000 mgm2 orally bid on day 1-14 q3 Arm B First line irinotecan 250 mgm2 IV infusion in 30 minutes on day 1 and capecitabine 1000 mgm2 orally bid on day 1-14 q3 until progression or unacceptable toxicity Second line oxaliplatin 130 mgm2 IV on day 1 and capecitabine 1000 mgm2 orally bid on day 1-14 q3 until progression or unacceptable toxicity
Patients will be followed by CT-scan every 9 weeks for response while on treatment or at any other moment when progression is suspected After cessation of chemotherapy patients will be followed every 3 months until death Clinical and laboratory toxicitysymptomatology will be graded according to NCI common criteria
Methodology Open randomised multicenter phase III study Randomisation by centre will be centralized 820 patiënts with histologically proven advanced CRC not amenable to curative surgery Measurable or evaluable disease Age 18 years and above WHO performance status 0-2
Test products
Arm A First line capecitabine capecitabine 1250 mgm2 orally bid on day 1-14 q3until progression or unacceptable toxicity Second line irinotecan 350 mgm2 IV infusion on day 1 q3until progression or unacceptable toxicity Third line oxaliplatin 130 mgm2 IV infusion on day 1 and capecitabine 1000 mgm2 orally bid on day 1-14 q3 Arm B First line irinotecan 250 mgm2 IV infusion in 30 minutes on day 1 and capecitabine 1000 mgm2 orally bid on day 1-14 q3 until progression or unacceptable toxicity Second line oxaliplatin 130 mgm2 IV on day 1 and capecitabine 1000 mgm2 orally bid on day 1-14 q3 until progression or unacceptable toxicity
Patients will be followed by CT-scan every 9 weeks for response while on treatment or at any other moment when progression is suspected After cessation of chemotherapy patients will be followed every 3 months until death Clinical and laboratory toxicitysymptomatology will be graded according to NCI common criteria
Detailed Description:
Objectives Primary objective
To assess the efficacy defined as overall survival of sequential versus combination chemotherapy for advanced CRC
Secondary objectives are to assess
To assess Tumour response CR PR or SD Progression free survival Quality of life Toxicity profile Methodology Open randomised multicenter phase III study Randomisation by centre will be centralized by IKC Number of patients 820 Main criteria for inclusion Histology and staging disease
Histologically proven advanced CRC not amenable to curative surgery
Of Note In case of a single metastasis histological or cytological proof of colorectal carcinoma should be obtained prior to randomisation
Measurable or evaluable disease Serum CEA as the only parameter for disease activity is not allowed
General conditions
Written informed consent
Age 18 years and above
WHO performance status 0-2
Adequate bone marrow function WBC 30 x 109L platelets 100 x 109L Hb 6 mmolL
Adequate hepatic function total bilirubin 1 5 x upper normal limit ASAT and ALAT 3 x upper normal limits in case of liver metastases 5 x upper normal limits
Adequate renal function creatinin 1 5 x upper normal limits Other
Expected adequacy of follow-up
Main criteria for exclusion General conditions
Pregnancy or lactation
Patients MF with reproductive potential not implementing adequate contraceptives measures
Prior or current history
Prior chemotherapy for advanced disease prior adjuvant chemotherapy is allowed provided that the last drug administration took place more than 6 months prior to randomisation
Serious concomitant diseases preventing the safe administration of chemotherapy or likely to interfere with the study assessments
Serious active infections
Inflammatory bowel disease or other diseases associated with chronic diarrhoea
Previous extensive irradiation of pelvis or abdomen
Other malignancies in the past 5 years with the exception of adequately treated carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin
Concomitant treatments
Concomitant or within 4 weeks before randomisation administration of any other experimental drug under investigation
Concurrent treatment with any other anti-cancer therapy Test product dose and mode of administration Arm A First line capecitabine
Every 3 weeks q 3
capecitabine 1250 mgm2 orally bid on day 1-14 This schedule will be continued until progression or unacceptable toxicity Continuation after 6 months without disease progression andor severe toxicity at the investigators discretion
Second line irinotecan
Every 3 weeks q 3
irinotecan 350 mgm2 IV infusion on day 1 This schedule will be continued until progression or unacceptable toxicity Continuation after 6 months without disease progression andor severe toxicity at the investigators discretion
Third line oxaliplatin plus capecitabine oxaliplatin 130 mgm2 IV infusion on day 1 and capecitabine 1000 mgm2 orally bid on day 1-14 This schedule will be continued until progression or unacceptable toxicity Continuation after 6 months without disease progression andor severe toxicity at the investigators discretion
Arm B First line irinotecan plus capecitabine
Every 3 weeks q 3
irinotecan 250 mgm2 IV infusion in 30 minutes on day 1 2 hours after discontinuation of the infusion followed by capecitabine 1000 mgm2 orally bid on day 1-14 This schedule will be continued until progression or unacceptable toxicity Continuation after 6 months without disease progression andor severe toxicity at the investigators discretion
Second line oxaliplatin plus capecitabine
Every 3 weeks q 3
oxaliplatin 130 mgm2 IV infusion in 2 hours on day 1 and capecitabine 1000 mgm2 orally bid on day 1-14 This schedule will be continued until progression or unacceptable toxicity Continuation after 6 months without disease progression andor severe toxicity at the investigators discretion
Duration of treatment and follow-up Treatment is continued until disease progression or unacceptable toxicity Patients will be followed by CT-scan every 9 weeks for response while on treatment or at any other moment when progression is suspected After cessation of chemotherapy patients will be followed every 3 months until death Death or progression should be reported whenever it occurs
Criteria for evaluation Efficacy All patients will be included in the survival analysis intent-to-treat All patients receiving 9 weeks of treatment ie 3 cycles will be considered evaluable for response unless documented progression occurred earlier
Safety profile Safety will be analysed in each treatment group Patients having received treatment doses are evaluable for toxicity Evaluation will be performed by patient and by cycle on the intent-to-treat population Clinical and laboratory toxicitysymptomatology will be graded according to NCI common criteria The adverse events which are not reported in NCI common criteria will be graded as mild moderate severe life threatening
Statistical methodology The expected median survival in Arm A standard arm is 14 months It is anticipated that the median survival in Arm B experimental arm will be 19 months 620 patients 310 in each arm are needed to show this increase in median survival 005 and 080
Stratification parameters Patients will be stratified for the following parameters
WHO performance status 0-1 vs 2
Serum LDH normal versus above normal
Prior adjuvant therapy versus no prior adjuvant therapy
Predominant localisation of metastases in the liver vs extrahepatic sites
Per participating institution
To assess the efficacy defined as overall survival of sequential versus combination chemotherapy for advanced CRC
Secondary objectives are to assess
To assess Tumour response CR PR or SD Progression free survival Quality of life Toxicity profile Methodology Open randomised multicenter phase III study Randomisation by centre will be centralized by IKC Number of patients 820 Main criteria for inclusion Histology and staging disease
Histologically proven advanced CRC not amenable to curative surgery
Of Note In case of a single metastasis histological or cytological proof of colorectal carcinoma should be obtained prior to randomisation
Measurable or evaluable disease Serum CEA as the only parameter for disease activity is not allowed
General conditions
Written informed consent
Age 18 years and above
WHO performance status 0-2
Adequate bone marrow function WBC 30 x 109L platelets 100 x 109L Hb 6 mmolL
Adequate hepatic function total bilirubin 1 5 x upper normal limit ASAT and ALAT 3 x upper normal limits in case of liver metastases 5 x upper normal limits
Adequate renal function creatinin 1 5 x upper normal limits Other
Expected adequacy of follow-up
Main criteria for exclusion General conditions
Pregnancy or lactation
Patients MF with reproductive potential not implementing adequate contraceptives measures
Prior or current history
Prior chemotherapy for advanced disease prior adjuvant chemotherapy is allowed provided that the last drug administration took place more than 6 months prior to randomisation
Serious concomitant diseases preventing the safe administration of chemotherapy or likely to interfere with the study assessments
Serious active infections
Inflammatory bowel disease or other diseases associated with chronic diarrhoea
Previous extensive irradiation of pelvis or abdomen
Other malignancies in the past 5 years with the exception of adequately treated carcinoma in situ of the cervix or squamous or basal cell carcinoma of the skin
Concomitant treatments
Concomitant or within 4 weeks before randomisation administration of any other experimental drug under investigation
Concurrent treatment with any other anti-cancer therapy Test product dose and mode of administration Arm A First line capecitabine
Every 3 weeks q 3
capecitabine 1250 mgm2 orally bid on day 1-14 This schedule will be continued until progression or unacceptable toxicity Continuation after 6 months without disease progression andor severe toxicity at the investigators discretion
Second line irinotecan
Every 3 weeks q 3
irinotecan 350 mgm2 IV infusion on day 1 This schedule will be continued until progression or unacceptable toxicity Continuation after 6 months without disease progression andor severe toxicity at the investigators discretion
Third line oxaliplatin plus capecitabine oxaliplatin 130 mgm2 IV infusion on day 1 and capecitabine 1000 mgm2 orally bid on day 1-14 This schedule will be continued until progression or unacceptable toxicity Continuation after 6 months without disease progression andor severe toxicity at the investigators discretion
Arm B First line irinotecan plus capecitabine
Every 3 weeks q 3
irinotecan 250 mgm2 IV infusion in 30 minutes on day 1 2 hours after discontinuation of the infusion followed by capecitabine 1000 mgm2 orally bid on day 1-14 This schedule will be continued until progression or unacceptable toxicity Continuation after 6 months without disease progression andor severe toxicity at the investigators discretion
Second line oxaliplatin plus capecitabine
Every 3 weeks q 3
oxaliplatin 130 mgm2 IV infusion in 2 hours on day 1 and capecitabine 1000 mgm2 orally bid on day 1-14 This schedule will be continued until progression or unacceptable toxicity Continuation after 6 months without disease progression andor severe toxicity at the investigators discretion
Duration of treatment and follow-up Treatment is continued until disease progression or unacceptable toxicity Patients will be followed by CT-scan every 9 weeks for response while on treatment or at any other moment when progression is suspected After cessation of chemotherapy patients will be followed every 3 months until death Death or progression should be reported whenever it occurs
Criteria for evaluation Efficacy All patients will be included in the survival analysis intent-to-treat All patients receiving 9 weeks of treatment ie 3 cycles will be considered evaluable for response unless documented progression occurred earlier
Safety profile Safety will be analysed in each treatment group Patients having received treatment doses are evaluable for toxicity Evaluation will be performed by patient and by cycle on the intent-to-treat population Clinical and laboratory toxicitysymptomatology will be graded according to NCI common criteria The adverse events which are not reported in NCI common criteria will be graded as mild moderate severe life threatening
Statistical methodology The expected median survival in Arm A standard arm is 14 months It is anticipated that the median survival in Arm B experimental arm will be 19 months 620 patients 310 in each arm are needed to show this increase in median survival 005 and 080
Stratification parameters Patients will be stratified for the following parameters
WHO performance status 0-1 vs 2
Serum LDH normal versus above normal
Prior adjuvant therapy versus no prior adjuvant therapy
Predominant localisation of metastases in the liver vs extrahepatic sites
Per participating institution
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None