Metformin and Insulin to Pancreatic Cancer Related Diabetes (Type 3c)

Administration of Metformin and Insulin to Pancreatic Cancer Related Diabetes Mellitus (Type 3c)

About 80% of patients with pancreatic adenocarcinoma have aberrant fasting blood glucose at the time of diagnosis. The consistent association between pancreatic cancer and diabetes mellitus has long been recognized and even been termed as "chicken and egg". Many reports have found that pancreatic cancer can result in diabetes, which is called type 3c diabetes. New-onset diabetes is commonly observed in pancreatic cancer patients and has been considered as a potential screening sign. Moreover, diabetes has been found as a predictor of poor outcome in pancreatic cancer.

Pancreatic cancer cells have a strong dependence on glucose and they are well-known for their sweet teeth. High glucose is associated with impaired immunologic reaction, intolerability to chemotherapy, radiotherapy and other major treatments, an increased risk of pancreatic surgery. Given the linkage between pancreatic cancer and diabetes or high blood glucose, a clinical trial is needed to validate the effect of metformin and insulin on regulating blood glucose in type 3c diabetes.

Study Overview

• Status: Recruiting
• Conditions: Diabete Mellitus; Pancretic Cancer
• Intervention / Treatment: Drug: Metformin or insulin treatment

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University
      • Contact: Guopei Luo, M.D., Ph.D.; Phone Number: +86-21-6417-5590; Email: luoguopei@fudanpci.org
      • Principal Investigator: Guopei Luo, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed content obtained prior to treatment
• Age ≥ 18 years and ≤ 80 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patients must have histologically confirmed pancreatic adenocarcinoma
• Fasting blood glucose ≥ 7.0 mmol/L（126 mg/dl）
• The expected survival after surgery ≥ 3 months

Exclusion Criteria:

• Active second primary malignancy or history of second primary malignancy
• Patients who have received any form of anti-tumor therapy before surgery, including chemotherapy, radiotherapy, interventional chemoembolization, radiofrequency ablation, and molecular targeted therapy
• Inflammation of the digestive tract, including pancreatitis, cholecystitis, cholangitis, etc
• Total bilirubin (TBIL) > institutional upper limit of normal (ULN)
• Pregnant or nursing women
• Patients who are unwilling or unable to comply with study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Metformin or insulin treatment

Drug: Metformin or insulin treatment; For patients with new-onset diabetes Fasting blood glucose 7-10 mmol/L, metformin 2 g/day, BID, PO; Fasting blood glucose 10-14 mmol/L, metformin 1 g/day, BID, PO, Novolin 30R Penfil 12 U before breakfast, 8 U; Fasting blood glucose > 14 mmol/L, metformin 1 g/day, BID, PO, Novolin 30R Penfil 16 U before breakfast, 10 U; Adjusting insulin dosage according to the monitor of fasting blood glucose.; For patients with history of diabetes Adjusting metformin or insulin dosage according to the monitor of fasting blood glucose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood glucose control rate	Blood glucose control rate before and after anti-diabetic administration	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1C control rate	HbA1C control rate before and after anti-diabetic administration	1 week

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum Carbohydrate Antigen 19-9 (CA19-9) From Baseline to Day 8.	Change of tumor biomarkers before and after anti-diabetic administration.Patients will collect CA19-9 values on the day of enrollment and on day 8.	1 week
Overall survival，OS	OS of subjects from recruiting to the time of death from any cause	At the end of Cycle 1 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Fudan University

Publications and helpful links

General Publications

• Pannala R, Basu A, Petersen GM, Chari ST. New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer. Lancet Oncol. 2009 Jan;10(1):88-95. doi: 10.1016/S1470-2045(08)70337-1.
• Sharma A, Kandlakunta H, Nagpal SJS, Feng Z, Hoos W, Petersen GM, Chari ST. Model to Determine Risk of Pancreatic Cancer in Patients With New-Onset Diabetes. Gastroenterology. 2018 Sep;155(3):730-739.e3. doi: 10.1053/j.gastro.2018.05.023. Epub 2018 Jun 11.
• Bragg F, Holmes MV, Iona A, Guo Y, Du H, Chen Y, Bian Z, Yang L, Herrington W, Bennett D, Turnbull I, Liu Y, Feng S, Chen J, Clarke R, Collins R, Peto R, Li L, Chen Z; China Kadoorie Biobank Collaborative Group. Association Between Diabetes and Cause-Specific Mortality in Rural and Urban Areas of China. JAMA. 2017 Jan 17;317(3):280-289. doi: 10.1001/jama.2016.19720.
• Yuan C, Rubinson DA, Qian ZR, Wu C, Kraft P, Bao Y, Ogino S, Ng K, Clancy TE, Swanson RS, Gorman MJ, Brais LK, Li T, Stampfer MJ, Hu FB, Giovannucci EL, Kulke MH, Fuchs CS, Wolpin BM. Survival among patients with pancreatic cancer and long-standing or recent-onset diabetes mellitus. J Clin Oncol. 2015 Jan 1;33(1):29-35. doi: 10.1200/JCO.2014.57.5688. Epub 2014 Nov 17.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 3, 2022
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: insulin; metformin; blood glucose
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: PTCA199-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No