Ignite Creation Date:
2024-05-05 @ 10:55 PM
Last Modification Date:
2024-10-26 @ 10:25 AM
Study NCT ID:
NCT01210911
Status:
COMPLETED
Last Update Posted:
2021-04-21
First Post:
2010-09-28
Brief Title:
Metformin Combined With Chemotherapy for Pancreatic Cancer
Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam AMC-UvA
Organization:
Academisch Medisch Centrum - Universiteit van Amsterdam AMC-UvA
Study Overview
Official Title:
A Phase II Randomized Placebo Controlled Study to Evaluate the Efficacy of the Combination of Gemcitabine Erlotinib and Metformin in Patients With Locally Advanced and Metastatic Pancreatic Cancer
Status:
COMPLETED
Status Verified Date:
2021-04
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:
GEM
Brief Summary:
Pancreatic cancer patients have one of the worst prognoses among all cancer types with a 5 year survival rate of less than 5 Despite significant changes during the last decade in our molecular knowledge on this disease the prognosis and management of pancreatic cancer have remained unchanged With the advances in molecular biology newer biologic agents such as erlotinib are adding some benefit to the conventional cytotoxic agents There is a growing body of literature suggesting that type 2 diabetes mellitus DM may be associated with the development of pancreatic cancer but this association is complex Because various DM medications can affect directly the key factors mediating the association between DM and pancreatic cancer understanding the effect of anti-diabetic therapies on pancreatic cancer is a critical step in fully characterizing the role of type 2 DM in the development of pancreatic cancer Indeed two epidemiologic studies have found that diabetic patients treated with metformin were less likely to develop cancer but those treated with insulin were more likely to die of various kinds cancer Not only does metformin ameliorate hyperglycemia and hyperinsulinemia both of which are associated with the adverse impact of DM on cancer metformin also has direct metabolic effects through activation of adenosine monophosphate-activated protein kinase AMPK AMPK regulates many metabolic enzymes and also inhibits the mammalian target of rapamycin mTOR pathway via phosphorylation and stabilization of the tumor suppressor gene TSC2 But there is an intensive cross-talk between various pathways Inhibition of the phosphoinositide 3-kinase PI3KAkt pathway of which mTOR is one of the effector proteins for instance may result in escape via the mitogen-activated protein kinase MAPK pathway and vice verse Indeed epidermal growth factor receptor EGFR activation leads to activation of the MAPK pathway and the PI3K pathway Thus since it is clear that blocking one pathway will not always be sufficient to produce a response in the presence of other activated pathways the best change of success will be realized when using a combination of agents that inhibit separate pathways known to be critical to the survival of the tumour In line with these observations combining a small molecule against the EGFR and inhibition of the PI3K pathway by metformin might account for potential candidates of the above combinatorial approach Therefore in this study the investigators want to determine the activity and safety of concurrent interruption of the MAPK and PI3K pathways by the EGFR tyrosine kinase inhibitor erlotinib and metformin combined with gemcitabine in patients with metastatic pancreatic cancer
Detailed Description:
In this phase II randomized placebo controlled study patients with locally advanced or metastatic pancreatic cancer will be randomized to treatment with gemcitabine erlotinib and metformin or gemcitabine erlotinib and placebo
Gemcitabine at a dose of 1000 mgm2 iv 30 minutes will be given weekly for 3 weeks followed by one week without treatment Erlotinib will be administered at a daily dose of 100 mg at least one hour before or 2 hours after the ingestion of food Metformin placebo will be administered at a dose of 500 mg twice daily If well tolerated the dose will be increased to 1000 mg twice daily in the second week
Gemcitabine at a dose of 1000 mgm2 iv 30 minutes will be given weekly for 3 weeks followed by one week without treatment Erlotinib will be administered at a daily dose of 100 mg at least one hour before or 2 hours after the ingestion of food Metformin placebo will be administered at a dose of 500 mg twice daily If well tolerated the dose will be increased to 1000 mg twice daily in the second week
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