Ignite Creation Date:
2024-05-06 @ 1:05 AM
Last Modification Date:
2024-10-26 @ 10:59 AM
Study NCT ID:
NCT01728818
Status:
UNKNOWN
Last Update Posted:
2017-07-19
First Post:
2012-07-05
Brief Title:
Afatinib as Cancer Therapy for Exocrine Pancreatic Tumours
Sponsor:
PD Dr med Volker Heinemann
Organization:
Ludwig-Maximilians - University of Munich
Study Overview
Official Title:
Gemcitabine in Combination With the Oral Irreversible ErbB Inhibitor Afatinib Versus Gemcitabine Alone in Patients With Metastatic Pancreatic Cancer an Explorative Randomized Phase II Trial
Status:
UNKNOWN
Status Verified Date:
2017-07
Last Known Status:
ACTIVE_NOT_RECRUITING
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:
ACCEPT
Brief Summary:
Single-agent gemcitabine is currently still regarded as one international standard of care for patients with advanced pancreatic cancer Burris 1997 4 The oral EGFR tyrosine kinase inhibitor erlotinib received EMEA-approval for the treatment of patients with metastatic pancreatic cancer in January 2007
In the pivotal phase III trial the combination of gemcitabine plus erlotinib was associated with a statistically significant prolongation of OS compared to single-agent gemcitabine however the absolute survival benefit was - for the overall study population - clinically moderate median OS 624 vs 591 months 1-year OS rate 23 vs 17 HR 082 p0038 Moore 2007 19
The recently presented FOLFIRINOX regimen shows enhanced activity in metastatic pancreatic cancer patients This regimen is however limited to patients with good performance status ECOG 0-1 no major comorbidity age 75 years and bilirubin 15 ULN Conroy 2011 6 The majority of pancreatic cancer patients will therefore not be treated with this regimen
Accordingly novel treatment concepts are urgently needed in pancreatic cancer and pre-clinical data indicate an important role of the EGFR1erbB2 receptor signalling in the pathogenesis of pancreatic adenocarcinoma Yeh 2007 24 A recent publication Larbouret 2010 16 indicates that the combination of cetuximab and trastuzumab induced superior antitumour activity in human pancreatic carcinoma xenografts compared to gemcitabine alone see also Larbouret 2007 15 Furthermore synergistic antitumour activity was observed when monoclonal antibodies directed against the EGFR1 and erbB2 were combined Ben-Kasus 2009 3 Based on these data there is a good rationale to further investigate the combined inhibition of the erbB family in pancreatic cancer patients
Afatinib BIBW 2992 is a novel irreversible EGFR1- and HER2 and HER4 inhibitor that is applied orally The purpose of the present trial is to investigate the erbB family inhibition by afatinib in patients with metastatic pancreatic cancer
In the planned trial afatinib will be applied at the dose 40 mgday that was chosen for the randomised phase III trial LUX 5 study that investigates afatinib plus weekly paclitaxel 80mgm2
Presently there is also a phase I study ongoing that investigates the combination of afatinib with gemcitabine ClinicalTrialsgov Identifier NCT01251653 U10-2249-02 Possibly the data will be available once the study is ready to start Otherwise a modification of the regimen will be planned once the respective data will be available
In this trial we integrate a translational project which may allow the identification of patients that primarily benefit from this novel treatment approach The availability of tumour tissue- and blood samples from each patient is therefore an important inclusion criterion
A 21 randomisation is chosen favouring the experimental arm since a large body of data is available on gemcitabine alone and since sufficient efficacy and toxicity data shall be gained in the experimental arm In addition the patients motivation to take part in the trial will be greatly enhanced by a greater chance to receive the experimental agent
In the pivotal phase III trial the combination of gemcitabine plus erlotinib was associated with a statistically significant prolongation of OS compared to single-agent gemcitabine however the absolute survival benefit was - for the overall study population - clinically moderate median OS 624 vs 591 months 1-year OS rate 23 vs 17 HR 082 p0038 Moore 2007 19
The recently presented FOLFIRINOX regimen shows enhanced activity in metastatic pancreatic cancer patients This regimen is however limited to patients with good performance status ECOG 0-1 no major comorbidity age 75 years and bilirubin 15 ULN Conroy 2011 6 The majority of pancreatic cancer patients will therefore not be treated with this regimen
Accordingly novel treatment concepts are urgently needed in pancreatic cancer and pre-clinical data indicate an important role of the EGFR1erbB2 receptor signalling in the pathogenesis of pancreatic adenocarcinoma Yeh 2007 24 A recent publication Larbouret 2010 16 indicates that the combination of cetuximab and trastuzumab induced superior antitumour activity in human pancreatic carcinoma xenografts compared to gemcitabine alone see also Larbouret 2007 15 Furthermore synergistic antitumour activity was observed when monoclonal antibodies directed against the EGFR1 and erbB2 were combined Ben-Kasus 2009 3 Based on these data there is a good rationale to further investigate the combined inhibition of the erbB family in pancreatic cancer patients
Afatinib BIBW 2992 is a novel irreversible EGFR1- and HER2 and HER4 inhibitor that is applied orally The purpose of the present trial is to investigate the erbB family inhibition by afatinib in patients with metastatic pancreatic cancer
In the planned trial afatinib will be applied at the dose 40 mgday that was chosen for the randomised phase III trial LUX 5 study that investigates afatinib plus weekly paclitaxel 80mgm2
Presently there is also a phase I study ongoing that investigates the combination of afatinib with gemcitabine ClinicalTrialsgov Identifier NCT01251653 U10-2249-02 Possibly the data will be available once the study is ready to start Otherwise a modification of the regimen will be planned once the respective data will be available
In this trial we integrate a translational project which may allow the identification of patients that primarily benefit from this novel treatment approach The availability of tumour tissue- and blood samples from each patient is therefore an important inclusion criterion
A 21 randomisation is chosen favouring the experimental arm since a large body of data is available on gemcitabine alone and since sufficient efficacy and toxicity data shall be gained in the experimental arm In addition the patients motivation to take part in the trial will be greatly enhanced by a greater chance to receive the experimental agent
Detailed Description:
None
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