NCT02978547

The Effects of Neoadjuvant Metformin on Tumour Cell Proliferation and Tumour Progression in Pancreatic Ductal Adenocarcinoma

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: British Columbia Cancer Agency · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a single arm, non-randomized phase II study of neoadjuvant metformin in resectable PDAC. Twenty patients will be enrolled and treated with metformin 500 mg BD for a minimum of 7 days, until 2 days prior to surgery. Patients will undergo laboratory investigations at baseline, prior to surgery and 4-10 weeks after surgery. Patients eligible for and consented to the optional MRI substudy will undergo diffusion-weighted MRI 1 to 14 days before surgery. At surgery, resected tumour and normal tissue will be collected and banked. FFPE specimens will be used for sectioning, histological analysis and IHC for Ki67 (cell proliferation marker), pAMPK, ACC targets, p53 and mTOR targets, apoptotic markers (Bax, Bcl-2, caspases 3, 8 and 9). Fresh frozen tumour and matched normal tissue samples will be used for western blot analysis of insulin and IGF receptors, total and activated ERK and Akt, and RNAseq analysis. Pre-metformin biopsy samples will be retrieved for molecular analysis. Fasting blood samples at baseline and before surgery will be analyzed for glucose and insulin levels. Plasma and whole blood will also be processed and banked for circulating tumour DNA analysis. Urine samples will be sent for metabolomic profiling.

Conditions

• Resectable Pancreatic Ductal Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Metformin Hydrochloride 500Mg Tablet	In the event of any grade 2 toxicities (with the exception of hyperglycemia), metformin will be withheld until improvement to ≤ grade 1, then restarted at a dose of 500 mg daily. In the event of grade ≥ 3 toxicities related to metformin, treatment will be discontinued. Metformin therapy will also be discontinued if serum lactate levels are above normal values.

Timeline

• Start date: 2019-01-01
• Primary completion: 2020-06-01
• Completion: 2021-01-01
• First posted: 2016-12-01
• Last updated: 2018-01-18

Locations

1 site across 1 country: Canada