A Phase 2 interventional study of Metformin Hydrochloride 500Mg Tablet in Resectable Pancreatic Ductal Adenocarcinoma, sponsored by British Columbia Cancer Agency. Status unknown at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-01-18.
Sponsored by British Columbia Cancer Agency · Phase 2, Interventional, and Treatment
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.
2,004 studies on the registry are indexed under Adenocarcinoma; 375 are open to participants now.
This study's planned enrollment of 20 is below the median of 45 across 1,553 interventional studies indexed under Adenocarcinoma.
Browse Adenocarcinoma studies →British Columbia Cancer Agency is the lead sponsor of 149 studies on the registry; 32 are open to participants now.
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Adequate hematologic, renal, and hepatic function as measured by the following laboratory assessments conducted within 7 days prior to the initiation of study treatment:
MRI sub-study:
Exclusion Criteria:
All patients will receive metformin 500 mg per oral twice daily with food for at least 7 days, until 2 days prior to surgery. Metformin therapy should be discontinued 2 days before surgery to reduce the risk of lactic acidosis associated with fasting.
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.
The effect of neoadjuvant metformin treatment on tumour cell proliferation in PDAC tumours
Assessment of Ki-67 fraction as assessed by IHC of pre- and post-metformin tumour samples.
Time frame: 6 months
R0 resection rates in patients undergoing curative PDAC resection
Proportion of patients with R0 resections.
Time frame: 6 months
The effect of metformin on glucose and insulin metabolism as assessed by serum marker, fasting GGT (mmol/L)
The marker of glucose and insulin metabolism will be reported with pre- and post-metformin values compared.
Time frame: 6 months
The effect of metformin on glucose and insulin metabolism as assessed by serum marker, fasting glucose (mmol/L)
The marker of glucose and insulin metabolism will be reported with pre- and post-metformin values compared.
Time frame: 6 months
The effect of metformin on glucose and insulin metabolism as assessed by serum marker, fasting insulin (mU/L)
The marker of glucose and insulin metabolism will be reported with pre- and post-metformin values compared.
Time frame: 6 months
The effect of metformin on glucose and insulin metabolism as assessed by serum marker, HOMA index
HOMA index is calculated from serum glucose and insulin. The marker of glucose and insulin metabolism will be reported with pre- and post-metformin values compared.
Time frame: 6 months
The effect of metformin on glucose and insulin metabolism as assessed by clinical marker, weight (kg)
The clinical marker will be reported with pre- and post-metformin values compared.
Time frame: 6 months
The effect of metformin on metabolomic profile of pre- and post-metformin samples
Serum and urine metabolomic profile. Comparison of metabolite levels in pre-and post-metformin samples.
Time frame: 6 months
Transcriptome sequencing (RNAseq) of pre- and post-treatment tumour samples.
To investigate the molecular signatures associated with metformin response Comparison of gene expression in pre-metformin biopsy samples and post-metformin resected tumour samples. Expression of altered genes to be validated by IHC in tumour sections.
Time frame: 6 months
Plasma ctDNA, measured as percentage of mutant to total DNA fragments in plasma
To assess the presence of ctDNA in resectable PDAC, and dynamic changes following treatment with metformin and surgical resection Proportion of patients with detectable plasma ctDNA at baseline. Comparison of values pre- and post-metformin and 4-10 weeks after surgery.
Time frame: 6 months
Correlation between imaging and pathologic parameters
To explore the correlation between apparent diffusion coefficient (ADC) on MRI and pathologic findings. ADC values will be individually compared to tumour differentiation and Ki-67 fraction on pathologic examination.
Time frame: 6 months
This study is status unknown, as verified in Jan 2018. You cannot join it, but the record below documents what was studied.
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British Columbia Cancer Agency