Monitoring and Managing Glucose Levels in People With Pancreatic Cancer

Study Overview
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Brief Summary
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This study will investigate whether or not it is feasible to closely monitor and manage glucose levels in people with pancreatic cancer. It will also investigate what impact glucose management may have on pancreatic cancer. This is a pilot study that will use continuous glucose monitors (CGM) to monitor glucose levels in approximately 50 participants with pancreatic cancer. Participants will receive standard chemotherapy with a combination of up to four drugs to treat their pancreatic cancer: oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin (FOLFIRINOX). To treat high glucose levels, participants will be randomly assigned to one of two groups: Group 1 will receive anti-hyperglycemic treatment as guided by an endocrinologist with the aim of maintaining glucose levels between 4 and 10 mmol/L; Group 2 will receive anti-hyperglycemic treatment if their glucose levels are above 15 mmol/L, which is standard care. Participants in both Groups 1 and 2 will receive standard anti-hyperglycemic treatments: metformin, insulin, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium glucose co-transporter (SGLT2) inhibitors, and dipeptidyl peptidase 4 (DPP-4) inhibitors. After 4 cycles of FOLFIRINOX, the CGM will be removed but any anti-hyperglycemic treatments will continue as needed. If participants discontinue treatment with FOLFIRINOX, they will continue to be followed for survival and subsequent anti-cancer therapy and will continue follow-up for glucose-related concerns at the discretion of their endocrinologist and/or medical oncologist.

Official Title
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Pancreatic Cancer Glucose Assessment and Regulation Study

Conditions
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Pancreatic Cancer, PDAC - Pancreatic Ductal Adenocarcinoma, Hyperglycemia

Intervention / Treatment
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* Procedure: Endocrinologist-directed target blood glucose level 4-10 mmol/L using data from a continuous glucose monitor (CGM)
* Other: Standard Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological/cytological diagnosis of pancreatic ductal adenocarcinoma (PDAC). Planned to undergo first-line systemic therapy with FOLFIRINOX. Age greater than or equal to 18 years. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Adequate bone marrow and organ function as defined by the following laboratory values: Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L. Platelet count greater than or equal to 75 x 10^9/L. Hemoglobin greater than or equal to 9.0 g/dL. Estimated glomerular filtration rate (GFR) by Cockroft-Gault equation OR 24 hour urine collection greater than or equal to 40 ml/min. Creatinine clearance greater than or equal to 40 mL/min using Cockcroft-Gault formula. Potassium within normal limits, or corrected with supplements. International normalized ratio (INR) less than or equal to 1.5. Total serum bilirubin less than or equal to 2 x upper limit of normal (ULN) (any elevated bilirubin should be asymptomatic at enrollment) except for participants with documented Gilbert's syndrome who may only be included if the total bilirubin less than or equal to 3 x ULN or direct bilirubin less than or equal to 1.5 x ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x ULN (or less than or equal to 5 x ULN if liver metastases are present). Able to understand and voluntarily sign the informed consent form. Able to comply with the study visit schedule and other protocol requirements. Able to swallow oral medications and has no contraindications to subcutaneous insulin injections. Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 at baseline. Life expectancy of more than 90 days as judged by the study doctor. Exclusion Criteria: Absence of distant or lymph node metastases. Participants with borderline resectable or locally advanced PDAC are not eligible. Received prior systemic therapy (chemotherapy or any other anti-cancer agent) for treatment of metastatic PDAC. Participants who received adjuvant chemotherapy after surgical resection of early stage disease are eligible. Currently receiving anti-cancer therapy (chemotherapy or any other anti-cancer agent). Not fit for combination chemotherapy as judged by the study doctor. Presence of brain metastases. Known diagnosis of type I diabetes where strict glucose control and close Endocrinology follow-up is already indicated. Known diagnosis of type II diabetes and already followed by Endocrinologist. Female participants with a positive pregnancy test. Participants who are not safe to include in the study as judged by the study doctor for any medical or non-medical reason. Unable to comply with study assessments and follow-up.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive Glucose Intervention<br>Participants will receive standard anti-hyperglycemic treatment as guided by an endocrinologist using a combination of data from a continuous glucose monitor (CGM) and standard blood work drawn prior to each cycle of chemotherapy. Treatment will aim to maintain glucose levels between 4 and 10 mmol/L. Participants will have real-time access to their glucose data via the CGM. | Procedure: Endocrinologist-directed target blood glucose level 4-10 mmol/L using data from a continuous glucose monitor (CGM)<br>* Standard anti-hyperglycemic treatment given as directed by an endocrinologist to maintain blood glucose level within 4-10 mmol/L based on data from a continuous glucose monitor (CGM) and standard blood work drawn prior to each cycle of chemotherapy. Participants will have access to their glucose data from the CGM.<br>|
| Other: Standard Care<br>Participants will receive standard anti-hyperglycemic treatment only if blood glucose level is above 15 mmol/L as measured from standard blood work drawn prior to each cycle of chemotherapy. Participants will wear a CGM but will not be able to view their glucose data. Participants may be referred to an endocrinologist at the discretion of their medical oncologist. | Other: Standard Care<br>* Standard anti-hyperglycemic treatment given only if blood glucose level is greater than 15 mmol/L as measured from standard blood work drawn prior to each cycle of chemotherapy. Participants will wear a continuous glucose monitor (CGM) but will not have access to their glucose data. Participants may be referred to an endocrinologist at the discretion of their medical oncologist.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of glucose levels maintained within range in Arm 1 compared to Arm 2 | The percentage of time each participant's glucose levels in Arm 1 and Arm 2 remained within the 4-10 mmol/L range during the fourth cycle of FOLFIRINOX treatment as measured by a continuous glucose monitor. | From the Cycle 4 FOLFIRINOX treatment date to the Cycle 5 FOLFIRINOX treatment date (each cycle is typically 14 days). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) in each study arm, as defined by RECIST 1.1 | The proportion of participants in each study arm who have a complete response (CR) or partial response (PR) to FOLFIRINOX treatment, as defined by RECIST 1.1. | From the date of the screening scan (within 28 days of first dose) until the date of confirmed progression, withdrawal, date of death, or end of study, whichever comes first, assessed up to 43 months. | 
| Progression-free survival (PFS) in each study arm from the initiation of FOLFIRINOX | The length of time from the first dose of FOLFIRINOX until the date of progressive disease (PD), as defined by RECIST 1.1, for participants in each study arm. | From the date of first dose of FOLFIRINOX until the date of confirmed progression, withdrawal, date of death, or end of study, whichever comes first, assessed up to 43 months. | 
| Overall survival (OS) in each study arm from the initiation of FOLFIRINOX | The length of time from the initiation of FOLFIRINOX that participants survive in each study arm. | From the date of first dose of FOLFIRINOX until the date of death or end of study, whichever comes first, assessed up to 43 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Continuous Glucose Monitor, Feasibility, Glycemic management, Endocrinologist, Intensive glucose intervention, Pilot, Glucose control, FOLFIRINOX