Ignite Creation Date:
2024-05-05 @ 11:39 PM
Last Modification Date:
2024-10-26 @ 10:37 AM
Study NCT ID:
NCT01389414
Status:
COMPLETED
Last Update Posted:
2015-05-28
First Post:
2011-07-01
Brief Title:
Panitumumab Plus Gemcitabine and Oxaliplatin GEMOXVersus GEMOX Alone to Treat Advanced Biliary Tract Adenocarcinoma
Sponsor:
Prof Massimo Aglietta
Organization:
Fondazione del Piemonte per lOncologia
Study Overview
Official Title:
Phase II Open-label Randomized Clinical Trial of Panitumumab Plus Gemcitabine and Oxaliplatin GEMOX Versus GEMOX Alone as First Line Treatment in Advanced Biliary Tract Adenocarcinoma
Status:
COMPLETED
Status Verified Date:
2015-05
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:
Vecti-BIL
Brief Summary:
This is a multi-centre phase II open-label randomized 11 parallel-arm study of panitumumab in combination with chemotherapy P-GEMOX versus chemotherapy alone GEMOX Eligible subjects will be enrolled and randomized to receive first-line combination therapy consisting of panitumumab and GEMOX experimental arm or GEMOX alone control armThe ame of the Stuy is to evaluate the clinical activity of the P-GEMOX Panitumumab and GEMOX combination compared to GEMOX alone in patients with previously untreated surgically unresectable or metastatic biliary tract carcinoma KRAS wild-typeand To evaluate the safety profile of the P-GEMOX combination to assess the objective response rate to assess overall survival to study the correlation between biomarkers with activity and efficacy
Detailed Description:
Study Phase Phase II Open-label Randomized
Indication First line treatment in advanced intrahepatic cholangiocarcinoma and extrahepatic biliary adenocarcinoma including gallbladder
Primary Objective To evaluate the clinical activity of the Panitumumab and GEMOX P-GEMOX combination compared to GEMOX alone in patients with previously untreated surgically unresectable or metastatic biliary tract carcinoma KRAS wild-type
Secondary Objectives To evaluate the safety profile of the P-GEMOX combination to assess the objective response rate to assess overall survival to study the correlation between biomarkers with activity and efficacy
Study Design Multi-centre phase II open-label randomized 11 parallel-arm study of panitumumab in combination with chemotherapy P-GEMOX versus chemotherapy alone GEMOX Eligible subjects will be enrolled and randomized to receive first-line combination therapy consisting of panitumumab and GEMOX experimental arm or GEMOX alone control arm
Prior to study entry and in order to confirm eligibility the investigator will review relevant clinical documents including existing radiological images to ensure the subject has previously untreated unresectable biliary tract adenocarcinoma including gallbladder
Treatment assignment will be done centrally via an Interactive Voice Response System IVRS using a permuted-block randomization stratified according to ECOG performance status PS 0 or 1 vs 2 and site of primary tumor intrahepatic cholangiocarcinoma vs extrahepatic biliary carcinoma including gallbladder
Panitumumab will be administered by intravenous IV infusion at a dose of 6 mgkg once every two weeks Q2W
GEMOX chemotherapy will be administered after the administration of panitumumab once Q2W
Each patient will be treated for a maximum of 12 cycles until disease progression PD unacceptable toxicity or patients refusal Patients in the experimental arm without tumor progression at the end of chemotherapy 12 GEMOX completed or interruption for unacceptable toxicity from chemotherapy will continue panitumumab 6 mgkg once Q2W until tumor progression
Following documentation of progressive disease patients will be followed-up for survival
Subjects will be evaluated for tumor progression every 8 weeks 1 week Tumor response assessment will be performed by the Investigator using the revised Response Evaluation Criteria in Solid Tumors RECIST guidelines version 11
Subjects with symptoms suggestive of PD should be evaluated for tumor progression at the time the symptoms occur
Endpoints
Primary Endpoint Progression-free survival PFS defined as the time from randomization to evidence of progression RECIST vers11 death or last radiographic assessment in absence of a PFS event
Secondary Endpoints Objective response rate RECIST vers11 Overall survival Safety defined as incidence and severity of adverse events Aes significant laboratory changes changes in vital signs incidence of concomitant medications changes from baseline over time in ECOG performance status incidence of dose adjustments over the treatment period and incidence of treatment limiting toxicities TLT
Exploratory EndpointsInvestigation into potential correlations between the activity of the combination regimen of panitumumab and GEMOX P-GEMOX on molecular markers Depending on the availability of tumor tissue the biomarkers will be analyzed with the following priority EGFr expression nucleotide changes in EGFr and BRAF cancer genes mutations of other genes involved in the activation of the EGFr pathway EGFr gene amplification
Sample Size Approximately 88 subjects
Investigational Product Dosage and Administration
Panitumumab will be administered as a 60 minute - 15 minutes IV infusion just prior to administration of chemotherapy at a dose of 6 mgkg on day 1 of each cycle Gemcitabine 1000mgsqm will be administered by intravenous infusion in accordance with the hospital guidelines for administration of Gemcitabine Gemcitabine should be reconstituted and administered as 1-hour infusion on day 1 of each cycle Oxaliplatin 100mgsqm will be administered by intravenous infusion in accordance with the hospital guidelines for administration of Oxaliplatin Oxaliplatin should be reconstituted and administered as 2-hour infusion on day 2 of each cycle
Dose Regimen
Arm A panitumumab 6 mgkg will be administered over 60 minute - 15 minutes on day 1 followed by Gemcitabine 1000mgsqm administered by intravenous infusion as 1-hour infusion on day 1 of each cycle Oxaliplatin 100mgsqm will be administered by intravenous infusion as 2-hour infusion on day 2 of each cycle
Arm B Gemcitabine 1000mgsqm will be administered by intravenous infusion as 1-hour infusion on day 1 of each cycle Oxaliplatin 100mgsqm will be administered by intravenous infusion as 2-hour infusion on day 2 of each cycle
Statistical Considerations This phase II design implies a direct but non-definitive screening comparison of the experimental therapeutic approach against a randomized standard-treatment control arm within a trial with a moderate sample size
Assuming an accrual time of 24 months and a follow-up time of 12 months accounting for a 10 loss to follow-up in both arms a total sample of 88 patients is expected to yield the necessary numbers of events if the accrual rate is constant
The log-rank analysis will be stratified by ECOG PS 0 to 1 vs 2 and site of primary tumor ie intrahepatic cholangiocarcinoma vs extrahepatic biliary tract carcinoma including gallbladder
Indication First line treatment in advanced intrahepatic cholangiocarcinoma and extrahepatic biliary adenocarcinoma including gallbladder
Primary Objective To evaluate the clinical activity of the Panitumumab and GEMOX P-GEMOX combination compared to GEMOX alone in patients with previously untreated surgically unresectable or metastatic biliary tract carcinoma KRAS wild-type
Secondary Objectives To evaluate the safety profile of the P-GEMOX combination to assess the objective response rate to assess overall survival to study the correlation between biomarkers with activity and efficacy
Study Design Multi-centre phase II open-label randomized 11 parallel-arm study of panitumumab in combination with chemotherapy P-GEMOX versus chemotherapy alone GEMOX Eligible subjects will be enrolled and randomized to receive first-line combination therapy consisting of panitumumab and GEMOX experimental arm or GEMOX alone control arm
Prior to study entry and in order to confirm eligibility the investigator will review relevant clinical documents including existing radiological images to ensure the subject has previously untreated unresectable biliary tract adenocarcinoma including gallbladder
Treatment assignment will be done centrally via an Interactive Voice Response System IVRS using a permuted-block randomization stratified according to ECOG performance status PS 0 or 1 vs 2 and site of primary tumor intrahepatic cholangiocarcinoma vs extrahepatic biliary carcinoma including gallbladder
Panitumumab will be administered by intravenous IV infusion at a dose of 6 mgkg once every two weeks Q2W
GEMOX chemotherapy will be administered after the administration of panitumumab once Q2W
Each patient will be treated for a maximum of 12 cycles until disease progression PD unacceptable toxicity or patients refusal Patients in the experimental arm without tumor progression at the end of chemotherapy 12 GEMOX completed or interruption for unacceptable toxicity from chemotherapy will continue panitumumab 6 mgkg once Q2W until tumor progression
Following documentation of progressive disease patients will be followed-up for survival
Subjects will be evaluated for tumor progression every 8 weeks 1 week Tumor response assessment will be performed by the Investigator using the revised Response Evaluation Criteria in Solid Tumors RECIST guidelines version 11
Subjects with symptoms suggestive of PD should be evaluated for tumor progression at the time the symptoms occur
Endpoints
Primary Endpoint Progression-free survival PFS defined as the time from randomization to evidence of progression RECIST vers11 death or last radiographic assessment in absence of a PFS event
Secondary Endpoints Objective response rate RECIST vers11 Overall survival Safety defined as incidence and severity of adverse events Aes significant laboratory changes changes in vital signs incidence of concomitant medications changes from baseline over time in ECOG performance status incidence of dose adjustments over the treatment period and incidence of treatment limiting toxicities TLT
Exploratory EndpointsInvestigation into potential correlations between the activity of the combination regimen of panitumumab and GEMOX P-GEMOX on molecular markers Depending on the availability of tumor tissue the biomarkers will be analyzed with the following priority EGFr expression nucleotide changes in EGFr and BRAF cancer genes mutations of other genes involved in the activation of the EGFr pathway EGFr gene amplification
Sample Size Approximately 88 subjects
Investigational Product Dosage and Administration
Panitumumab will be administered as a 60 minute - 15 minutes IV infusion just prior to administration of chemotherapy at a dose of 6 mgkg on day 1 of each cycle Gemcitabine 1000mgsqm will be administered by intravenous infusion in accordance with the hospital guidelines for administration of Gemcitabine Gemcitabine should be reconstituted and administered as 1-hour infusion on day 1 of each cycle Oxaliplatin 100mgsqm will be administered by intravenous infusion in accordance with the hospital guidelines for administration of Oxaliplatin Oxaliplatin should be reconstituted and administered as 2-hour infusion on day 2 of each cycle
Dose Regimen
Arm A panitumumab 6 mgkg will be administered over 60 minute - 15 minutes on day 1 followed by Gemcitabine 1000mgsqm administered by intravenous infusion as 1-hour infusion on day 1 of each cycle Oxaliplatin 100mgsqm will be administered by intravenous infusion as 2-hour infusion on day 2 of each cycle
Arm B Gemcitabine 1000mgsqm will be administered by intravenous infusion as 1-hour infusion on day 1 of each cycle Oxaliplatin 100mgsqm will be administered by intravenous infusion as 2-hour infusion on day 2 of each cycle
Statistical Considerations This phase II design implies a direct but non-definitive screening comparison of the experimental therapeutic approach against a randomized standard-treatment control arm within a trial with a moderate sample size
Assuming an accrual time of 24 months and a follow-up time of 12 months accounting for a 10 loss to follow-up in both arms a total sample of 88 patients is expected to yield the necessary numbers of events if the accrual rate is constant
The log-rank analysis will be stratified by ECOG PS 0 to 1 vs 2 and site of primary tumor ie intrahepatic cholangiocarcinoma vs extrahepatic biliary tract carcinoma including gallbladder
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