Ignite Creation Date:
2024-05-05 @ 9:50 PM
Last Modification Date:
2024-10-26 @ 10:10 AM
Study NCT ID:
NCT00975897
Status:
COMPLETED
Last Update Posted:
2013-12-19
First Post:
2009-09-11
Brief Title:
Study of Tumor Tissue Testing in Selecting Treatment for Patients With Metastatic or Locally Advanced Colorectal Cancer
Sponsor:
Medical Research Council
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
FOCUS 3 - A Study to Determine the Feasibility of Molecular Selection of Therapy Using KRAS BRAF and Topo-1 in Patients With Metastatic or Locally Advanced Colorectal Cancer
Status:
COMPLETED
Status Verified Date:
2011-08
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:
RATIONALE Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer It may also help doctors select the best treatment for patients and predict their response to treatment
PURPOSE This randomized phase IIIII trial is studying how well tumor tissue testing works in selecting treatment for patients with metastatic or locally advanced colorectal cancer
PURPOSE This randomized phase IIIII trial is studying how well tumor tissue testing works in selecting treatment for patients with metastatic or locally advanced colorectal cancer
Detailed Description:
OBJECTIVES
Primary - Feasibility Study
To determine the proportion of consenting patients that can provide a formalin-fixed paraffin-embedded block containing tumor
To determine the feasibility of topoisomerase-1 topo-1 IHC and K-ras BRAF mutational status determination being completed with 10 working days of initial consent
To determine reproducibility of results between reference laboratories
To determine the real costs of molecular testing
To determine the patients ability to comprehend the study and their attitude during the waiting period for testing
To assess patients ability to fully comprehend the trial as explained to them
Secondary - Feasibility Study
To further identify the EGFR-responsive subset within the K-ras wildtype population
Primary - Definitive Study
Compare the clinical outcomes of patients with metastatic or locally advanced colorectal cancer and low topo-1-expressing tumors treated with fluorouracil alone versus irinotecan hydrochloride fluorouracil and leucovorin calcium IrMdG
Compare the progression-free survival of patients with high topo-1-expressing tumors treated with oxaliplatin and IrMdG versus IrMdG alone
Compare the response rate in patients with K-ras wildtype tumor treated with cetuximab and IrMdG versus IrMdG alone
Compare the response rate in patients with K-ras mutant tumors who are unlikely to respond to EGFR inhibition treated with bevacizumab and IrMdG versus IrMdG alone
OUTLINE This is a multicenter 2-part study
Part I feasibility study Once consent for tissue block release has been obtained and patient is registered the block is requested from the Pathology Department This begins the 10 working-day time line Treatment commences once the results of the testing are known The following evaluations are performed during this period
The frequency of EGFR gene amplification on FISH PI3K gene mutation PTEN loss by IHC estimation of mRNA for EGFR ligands amphiregulin and epiregulin and other protein assessments
An evaluation of the impact on the use or further investigation of these markers in the main study
Patients consenting to trial entry and if agreeable to data collection patients refusing trial entry complete a questionnaire assessing patients ability to fully comprehend the trial as explained to them
Patients are interviewed before allocation of treatment about their attitudes about the waiting period necessary for tumor testing
Part II definitive study Patients are stratified according to availability of both lab tests K-ras mutation yes vs no BRAF mutation yes vs no and topoisomerase-1 topo-1 expression low vs high Patients are assigned to 1 of 4 treatment groups based on their biomarker test results
Group 1 low topo-1 and both K-ras and BRAF wildtype Patients are randomized to 1 of 3 treatment arms
Arm I regimen A IrMdG Patients receive irinotecan hydrochloride IV over 30 minutes leucovorin calcium IV over 2 hours and fluorouracil IV bolus followed by infusion over 46 hours on day 1 Treatment repeats every 2 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity
Arm II regimen B MdG Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV bolus followed by infusion over 46 hours on day 1 Treatment repeats every 2 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity
Arm III regimen D IrMdG and cetuximab Patients receive cetuximab IV over 1-2 hours irinotecan hydrochloride IV over 30 minutes leucovorin calcium IV over 2 hours and fluorouracil IV bolus followed by infusion over 46 hours on day 1 Treatment repeats every 2 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity
Group 2 low topo-1 and either K-ras or BRAF mutation Patients are randomized to 1 of 3 treatment arms
Arm I regimen A IrMdG Patients receive irinotecan hydrochloride leucovorin calcium and fluorouracil as in group 1 arm I
Arm II regimen B MdG Patients receive leucovorin calcium and fluorouracil as in group 1 arm II
Arm III regimen E IrMdG and bevacizumab Patients receive bevacizumab IV over 30-90 minutes irinotecan hydrochloride IV over 30 minutes leucovorin calcium IV over 2 hours and fluorouracil IV bolus followed by infusion over 46 hours on day 1 Treatment repeats every 2 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity
Group 3 high topo-1 and both K-ras and BRAF wildtype Patients are randomized to 1 of 3 treatment arms
Arm I regimen A IrMdG Patients receive irinotecan hydrochloride leucovorin calcium and fluorouracil as in group 1 arm I
Arm II regimen C IrOxMdG Patients receive irinotecan hydrochloride IV over 30 minutes leucovorin calcium IV over 2 hours oxaliplatin IV over 2 hours and fluorouracil IV bolus followed by infusion over 46 hours on day 1 Treatment repeats every 2 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity
Arm III regimen D IrMdG and cetuximab Patients receive cetuximab irinotecan hydrochloride leucovorin calcium and fluorouracil IV as in group 1 arm III
Group 4 high topo-1 and either K-ras or BRAF mutation Patients are randomized to 1 of 3 treatment arms
Arm I regimen A IrMdG Patients receive irinotecan hydrochloride leucovorin calcium and fluorouracil as in group 1 arm I
Arm II regimen C IrOxMdG Patients receive irinotecan hydrochloride leucovorin calcium oxaliplatin and fluorouracil as in group 3 arm II
Arm III regimen E IrMdG and bevacizumab Patients receive bevacizumab irinotecan hydrochloride leucovorin calcium and fluorouracil IV as group 2 arm III
After completion of study therapy patients are followed up periodically
PROJECTED ACCRUAL A total of 240 patients will be accrued for the feasibility study and approximately 3000 patients will be accrued for the definitive study
Primary - Feasibility Study
To determine the proportion of consenting patients that can provide a formalin-fixed paraffin-embedded block containing tumor
To determine the feasibility of topoisomerase-1 topo-1 IHC and K-ras BRAF mutational status determination being completed with 10 working days of initial consent
To determine reproducibility of results between reference laboratories
To determine the real costs of molecular testing
To determine the patients ability to comprehend the study and their attitude during the waiting period for testing
To assess patients ability to fully comprehend the trial as explained to them
Secondary - Feasibility Study
To further identify the EGFR-responsive subset within the K-ras wildtype population
Primary - Definitive Study
Compare the clinical outcomes of patients with metastatic or locally advanced colorectal cancer and low topo-1-expressing tumors treated with fluorouracil alone versus irinotecan hydrochloride fluorouracil and leucovorin calcium IrMdG
Compare the progression-free survival of patients with high topo-1-expressing tumors treated with oxaliplatin and IrMdG versus IrMdG alone
Compare the response rate in patients with K-ras wildtype tumor treated with cetuximab and IrMdG versus IrMdG alone
Compare the response rate in patients with K-ras mutant tumors who are unlikely to respond to EGFR inhibition treated with bevacizumab and IrMdG versus IrMdG alone
OUTLINE This is a multicenter 2-part study
Part I feasibility study Once consent for tissue block release has been obtained and patient is registered the block is requested from the Pathology Department This begins the 10 working-day time line Treatment commences once the results of the testing are known The following evaluations are performed during this period
The frequency of EGFR gene amplification on FISH PI3K gene mutation PTEN loss by IHC estimation of mRNA for EGFR ligands amphiregulin and epiregulin and other protein assessments
An evaluation of the impact on the use or further investigation of these markers in the main study
Patients consenting to trial entry and if agreeable to data collection patients refusing trial entry complete a questionnaire assessing patients ability to fully comprehend the trial as explained to them
Patients are interviewed before allocation of treatment about their attitudes about the waiting period necessary for tumor testing
Part II definitive study Patients are stratified according to availability of both lab tests K-ras mutation yes vs no BRAF mutation yes vs no and topoisomerase-1 topo-1 expression low vs high Patients are assigned to 1 of 4 treatment groups based on their biomarker test results
Group 1 low topo-1 and both K-ras and BRAF wildtype Patients are randomized to 1 of 3 treatment arms
Arm I regimen A IrMdG Patients receive irinotecan hydrochloride IV over 30 minutes leucovorin calcium IV over 2 hours and fluorouracil IV bolus followed by infusion over 46 hours on day 1 Treatment repeats every 2 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity
Arm II regimen B MdG Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV bolus followed by infusion over 46 hours on day 1 Treatment repeats every 2 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity
Arm III regimen D IrMdG and cetuximab Patients receive cetuximab IV over 1-2 hours irinotecan hydrochloride IV over 30 minutes leucovorin calcium IV over 2 hours and fluorouracil IV bolus followed by infusion over 46 hours on day 1 Treatment repeats every 2 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity
Group 2 low topo-1 and either K-ras or BRAF mutation Patients are randomized to 1 of 3 treatment arms
Arm I regimen A IrMdG Patients receive irinotecan hydrochloride leucovorin calcium and fluorouracil as in group 1 arm I
Arm II regimen B MdG Patients receive leucovorin calcium and fluorouracil as in group 1 arm II
Arm III regimen E IrMdG and bevacizumab Patients receive bevacizumab IV over 30-90 minutes irinotecan hydrochloride IV over 30 minutes leucovorin calcium IV over 2 hours and fluorouracil IV bolus followed by infusion over 46 hours on day 1 Treatment repeats every 2 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity
Group 3 high topo-1 and both K-ras and BRAF wildtype Patients are randomized to 1 of 3 treatment arms
Arm I regimen A IrMdG Patients receive irinotecan hydrochloride leucovorin calcium and fluorouracil as in group 1 arm I
Arm II regimen C IrOxMdG Patients receive irinotecan hydrochloride IV over 30 minutes leucovorin calcium IV over 2 hours oxaliplatin IV over 2 hours and fluorouracil IV bolus followed by infusion over 46 hours on day 1 Treatment repeats every 2 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity
Arm III regimen D IrMdG and cetuximab Patients receive cetuximab irinotecan hydrochloride leucovorin calcium and fluorouracil IV as in group 1 arm III
Group 4 high topo-1 and either K-ras or BRAF mutation Patients are randomized to 1 of 3 treatment arms
Arm I regimen A IrMdG Patients receive irinotecan hydrochloride leucovorin calcium and fluorouracil as in group 1 arm I
Arm II regimen C IrOxMdG Patients receive irinotecan hydrochloride leucovorin calcium oxaliplatin and fluorouracil as in group 3 arm II
Arm III regimen E IrMdG and bevacizumab Patients receive bevacizumab irinotecan hydrochloride leucovorin calcium and fluorouracil IV as group 2 arm III
After completion of study therapy patients are followed up periodically
PROJECTED ACCRUAL A total of 240 patients will be accrued for the feasibility study and approximately 3000 patients will be accrued for the definitive study
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EU-20960 | None | None | None |
| UKM-MRC-FOCUS3-CR12 | None | None | None |
| EUDRACT-2008-008323-15 | None | None | None |
| ISRCTN83171665 | None | None | None |