Glucose Monitoring for Pancreatic Cancer

(PEGASUS Trial)

Recruiting at 1 trial location

Overseen By Daniel Renouf, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: British Columbia Cancer Agency

Disqualifiers: Brain metastases, Type I diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether managing blood sugar levels can impact pancreatic cancer treatment. Participants will use a continuous glucose monitor (CGM) to track glucose levels while receiving standard chemotherapy. The trial includes two groups: one will receive more frequent anti-hyperglycemic treatments (such as Metformin, Insulin, GLP-1 Receptor Agonists, SGLT2 Inhibitors, and DPP-4 Inhibitors) to maintain glucose levels between 4 and 10 mmol/L, while the other will receive treatment only if levels exceed 15 mmol/L. Participants diagnosed with pancreatic ductal adenocarcinoma who plan to start FOLFIRINOX chemotherapy might be a good fit. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could improve future treatment strategies.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop your current medications. However, you will receive standard chemotherapy and may receive additional treatments to manage glucose levels. It's best to discuss your current medications with the study doctor.

What prior data suggests that continuous glucose monitoring is safe for people with pancreatic cancer?

Research has shown that continuous glucose monitors (CGMs) are generally safe for individuals with long-term conditions like diabetes. Studies have found that CGMs help maintain stable blood sugar levels without causing major side effects.

Regarding the blood sugar treatments in this study, such as metformin, insulin, GLP-1 receptor agonists, SGLT2 inhibitors, and DPP-4 inhibitors, research indicates they are well-tolerated. Metformin and insulin have been used for many years and are widely considered safe for managing blood sugar. Recent studies suggest that SGLT2 inhibitors and GLP-1 receptor agonists might even lower the risk of developing certain cancers, including pancreatic cancer. These findings support their safety for individuals with pancreatic cancer.

Overall, both CGM use and the blood sugar treatments in this study have good safety records based on previous research. However, discussing any concerns with a healthcare provider before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it combines continuous glucose monitoring (CGM) with anti-hyperglycemic treatments to manage blood sugar levels in pancreatic cancer patients. Unlike standard care, which only intervenes when glucose levels spike above 15 mmol/L, the intensive intervention arm uses real-time CGM data to maintain glucose levels between 4 and 10 mmol/L, potentially improving patient outcomes. This approach allows for personalized and timely adjustments to treatment based on continuous feedback, offering a more proactive and precise management strategy compared to traditional methods.

What evidence suggests that continuous glucose monitoring is effective for managing glucose levels in pancreatic cancer patients?

Research has shown that continuous glucose monitors (CGMs) can help individuals with diabetes better control their blood sugar and reduce episodes of low blood sugar. This is promising for those with pancreatic cancer, as managing blood sugar can be challenging due to the disease and its treatments. In this trial, participants in the Intensive Glucose Intervention arm will use CGMs to receive real-time blood sugar information, aiding treatment decisions. They will receive standard anti-hyperglycemic treatment guided by an endocrinologist. Medications like metformin and insulin effectively manage high blood sugar in diabetes, helping to stabilize blood sugar levels. Other treatments, such as GLP-1 receptor agonists, SGLT2 inhibitors, and DPP-4 inhibitors, also lower blood sugar in different ways. While these treatments are well-established for diabetes, their use with CGMs in this trial may offer better blood sugar control for those with pancreatic cancer. Participants in the Standard Care arm will receive standard anti-hyperglycemic treatment only if blood glucose levels exceed 15 mmol/L, and they will wear a CGM without access to real-time data. ^{6 7 8 9 10}

Who Is on the Research Team?

Daniel J Renouf, MD

Principal Investigator

BC Cancer

Are You a Good Fit for This Trial?

This trial is for adults over 18 with pancreatic cancer who are about to start their first chemotherapy treatment using FOLFIRINOX. They should be relatively healthy and active (ECOG status 0-1) with certain blood counts and kidney function levels within a specific range.

Inclusion Criteria

My blood tests show my organs and bone marrow are working well.

Able to comply with the study visit schedule and other protocol requirements

I can take pills and have no issues with insulin shots.

Exclusion Criteria

Unable to comply with study assessments and follow-up

I am currently undergoing treatment for cancer.

I am pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive standard chemotherapy with FOLFIRINOX and are monitored using continuous glucose monitors (CGM). Anti-hyperglycemic treatments are administered based on glucose levels.

8 weeks

4 cycles of chemotherapy, each cycle typically 14 days

Follow-up

Participants are monitored for survival, subsequent anti-cancer therapy, and glucose-related concerns after discontinuation of FOLFIRINOX.

6 months

Long-term follow-up

Participants continue to be followed for survival and glucose management at the discretion of their endocrinologist and/or medical oncologist.

Up to 43 months

What Are the Treatments Tested in This Trial?

Interventions

• Anti-hyperglycemic Treatments (Metformin, Insulin, GLP-1 Receptor Agonists, SGLT2 Inhibitors, DPP-4 Inhibitors)
• Continuous Glucose Monitor (CGM)

Trial Overview The study tests if managing glucose levels between 4-10 mmol/L using continuous monitoring improves outcomes in pancreatic cancer patients, compared to standard care where treatment starts if glucose exceeds 15 mmol/L.

How Is the Trial Designed?

Group I: Standard Care Experimental Treatment 1 Intervention

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.

Group II: Intensive Glucose Intervention Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Lustgarten Foundation

Collaborator

Trials

27

Recruited

5,500+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Published Research Related to This Trial

Dipeptidyl peptidase-4 (DPP-4) inhibitors, including linagliptin, are effective treatments for type-2 diabetes and can be used alone or with other diabetes medications.

Beyond diabetes management, DPP-4 inhibitors may have potential benefits for conditions like obesity, cardiovascular disease, and inflammation, suggesting their versatility in treating various health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linagliptin and newer DPP-4 inhibitors: newer uses and newer indications. Kalra, S., Unnikrishnan, AG., Agrawal, N., et al.[2019]

In a study involving 36 patients with type 2 diabetes, switching from DPP-4 inhibitors to dapagliflozin did not show significant improvements in glucose fluctuation compared to continuing DPP-4 inhibitors while on insulin therapy.

However, dapagliflozin treatment was associated with reductions in body mass index and albuminuria, suggesting potential metabolic benefits for patients with type 2 diabetes on insulin, despite no significant difference in glucose control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial comparing the effects of dapagliflozin and DPP-4 inhibitors on glucose variability and metabolic parameters in patients with type 2 diabetes mellitus on insulin. Nomoto, H., Miyoshi, H., Sugawara, H., et al.[2020]

Saxagliptin significantly reduces glycosylated hemoglobin (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM), with reductions ranging from -0.72% to -0.90% compared to -0.27% with placebo, based on data from 11 Phase III clinical trials.

Saxagliptin is well tolerated, with common side effects including upper respiratory infections and urinary tract infections, and it does not increase cardiovascular risk compared to other treatments, making it a safe option for managing T2DM, especially in combination with other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saxagliptin: a clinical review in the treatment of type 2 diabetes mellitus. Kania, DS., Gonzalvo, JD., Weber, ZA.[2022]

In a study involving 13 type 2 diabetes patients on insulin therapy, adding sitagliptin significantly reduced 24-hour mean glucose levels and glucose variability, indicating its effectiveness in improving glycemic control.

The addition of sitagliptin did not increase the risk of hypoglycemia, suggesting it is a safe option for enhancing postprandial glucose management in patients already using insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of add-on treatment with sitagliptin on narrowing the range of glucose fluctuations in Japanese type 2 diabetes patients receiving insulin therapy. Mori, Y., Taniguchi, Y., Miyazaki, S., et al.[2022]

DPP-4 inhibitors, including saxagliptin, linagliptin, and alogliptin, are widely used in managing type 2 diabetes, with significant financial investment indicating their importance in therapy.

Recent cardiovascular outcomes studies suggest that these medications not only help lower blood glucose levels but may also have implications for cardiovascular health, although specific results from these studies are not detailed in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the 'gliptins'. [2017]

Incretin-based therapies, such as GLP-1 receptor agonists and DPP-4 inhibitors, effectively manage blood sugar levels in type 2 diabetes patients with minimal risk of causing low blood sugar episodes.

While there are inconsistent reports of low-grade chronic pancreatitis in animal studies and some cases of acute pancreatitis in humans, current clinical data suggest that these therapies are safe regarding the risk of pancreatic cancer, although the potential link between chronic pancreatitis and cancer remains a concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incretin based therapy and pancreatic cancer: Realising the reality. Suryadevara, V., Roy, A., Sahoo, J., et al.[2023]

In a pilot study involving Japanese patients with type 2 diabetes, sitagliptin significantly reduced average 24-hour blood glucose levels and improved glycemic fluctuations, indicating its efficacy in managing diabetes.

The study showed that sitagliptin not only lowered blood glucose levels but also decreased the time spent in hyperglycemic states, suggesting it can help stabilize blood sugar throughout the day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of sitagliptin on 24-h glycemic changes in Japanese patients with type 2 diabetes assessed using continuous glucose monitoring. Mori, Y., Taniguchi, Y., Matsuura, K., et al.[2015]

A systematic review of 11 studies involving 730,664 patients with diabetes found that the use of sulfonylureas (SUs) is associated with a 70% increased risk of pancreatic cancer, while metformin, insulin, and thiazolidinediones (TZDs) showed no significant association with pancreatic cancer risk.

The analysis highlighted considerable variability among studies, suggesting that confounding factors may influence results, and emphasized the need for future well-designed prospective studies to clarify the relationship between anti-diabetic medications and pancreatic cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-diabetic medications and risk of pancreatic cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Singh, S., Singh, PP., Singh, AG., et al.[2018]

Liraglutide is an effective treatment for type 2 diabetes, reducing hemoglobin A1c levels by 0.8% to 1.5%, and is safe for patients at risk of hypoglycemia due to its low incidence of this side effect.

It is particularly beneficial for overweight or obese patients, as it not only helps control blood sugar but also promotes weight loss of about 2%-4% of initial body weight, although nausea can occur but is typically manageable with careful dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pearls for initiating and utilizing liraglutide in patients with type 2 diabetes. Gross, B.[2015]

Liraglutide, a GLP-1 receptor agonist, enhances the sensitivity of gemcitabine-resistant pancreatic cancer cells to chemotherapy by promoting apoptosis and inhibiting cell growth, as shown in both in vitro and in vivo studies.

The study found that liraglutide increases the expression of GLP-1R and PKA in resistant cancer cells, and its effects can be reversed by blocking these pathways, indicating a specific mechanism of action that could benefit patients with pancreatic cancer and diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of GLP-1 receptor enhances the chemosensitivity of pancreatic cancer cells. Zhao, HJ., Jiang, X., Hu, LJ., et al.[2022]

Saxagliptin, a DPP-4 inhibitor, significantly reduces HbA1c levels in type 2 diabetes patients when used alone or in combination with common medications like metformin and glyburide, based on a 24-week phase 3 clinical trial involving multiple studies.

The treatment was well tolerated, showed a low risk of hypoglycemia, and did not cause weight gain, making it a safe and effective option for managing blood sugar levels in type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of saxagliptin as monotherapy or adjunct therapy in the treatment of type 2 diabetes. Sharma, MD.[2021]

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