Glucose Monitoring for Pancreatic Cancer
(PEGASUS Trial)
Recruiting in Palo Alto (17 mi)
Overseen byErica Tsang, MD, MPH
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: British Columbia Cancer Agency
Disqualifiers: Brain metastases, Type I diabetes, others
No Placebo Group
Trial Summary
What is the purpose of this trial?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.
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 evidence supports the effectiveness of the drugs used in glucose monitoring for pancreatic cancer?
Some studies suggest that GLP-1 receptor agonists, like liraglutide, may enhance the effectiveness of chemotherapy in pancreatic cancer cells, making them more sensitive to treatment. Additionally, sitagliptin, a DPP-4 inhibitor, has been shown to help control blood sugar levels in diabetes patients, which could be beneficial for managing glucose levels in pancreatic cancer patients.
12345Is glucose monitoring and related treatments generally safe for humans?
The treatments mentioned, such as DPP-4 inhibitors like saxagliptin and liraglutide, have been studied for type 2 diabetes and are generally considered safe with a low risk of severe side effects. Common side effects include nausea for liraglutide, which is usually temporary, and a low risk of hypoglycemia (low blood sugar) for saxagliptin when used alone.
23678How does the drug used in glucose monitoring for pancreatic cancer differ from other treatments?
The drug used in glucose monitoring for pancreatic cancer may involve sitagliptin, a DPP-4 inhibitor, which is unique because it helps manage blood sugar levels by reducing glucose fluctuations, a feature not typically associated with standard cancer treatments.
2691011Eligibility Criteria
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.
I am 18 years old or older.
Able to comply with the study visit schedule and other protocol requirements
+17 more
Exclusion Criteria
Unable to comply with study assessments and follow-up
I am currently undergoing treatment for cancer.
I am pregnant.
+7 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Standard CareExperimental Treatment1 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 InterventionExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
British Columbia CancerVancouver, Canada
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Who Is Running the Clinical Trial?
British Columbia Cancer AgencyLead Sponsor
University of British ColumbiaCollaborator
References
Incretin based therapy and pancreatic cancer: Realising the reality. [2023]Incretin-based therapies like glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors help maintain the glycaemic control in patients with type 2 diabetes mellitus with additional systemic benefits and little risk of hypoglycaemia. These medications are associated with low-grade chronic pancreatitis in animal models inconsistently. The incidence of acute pancreatitis was also reported in some human studies. This inflammation provides fertile ground for developing pancreatic carcinoma (PC). Although the data from clinical trials and population-based studies have established safety regarding PC, the pathophysiological possibility that low-grade chronic pancreatitis leads to PC remains. We review the existing literature and describe the relationship between incretin-based therapies and PC.
Effects of add-on treatment with sitagliptin on narrowing the range of glucose fluctuations in Japanese type 2 diabetes patients receiving insulin therapy. [2022]In an earlier continuous glucose monitoring (CGM)-based study, we reported that sitagliptin not only reduced 24-h mean glucose levels but also suppressed postprandial glucose increases, thus reducing the range of glycemic fluctuations in type 2 diabetes patients. In this study, we investigated whether sitagliptin might provide similar benefits in type 2 diabetes patients receiving insulin therapy by using CGM.
Saxagliptin: a clinical review in the treatment of type 2 diabetes mellitus. [2022]Some conventional therapies for type 2 diabetes mellitus (T2DM) fail to address the progressive nature of the disease, and as a result, they may become ineffective in maintaining normoglycemia. Antihyperglycemic agents have been developed to target incretin hormones, specifically glucagon-like peptide (GLP)-1. Incretin analogues and agents that delay GLP-1 degradation, the dipeptidyl peptidase (DPP)-4 inhibitors, offer mechanisms of action that may improve T2DM management. Saxagliptin was approved by the US Food and Drug Administration in July 2009 and by the European Medicines Evaluation Agency in October 2009 for use as monotherapy or in combination regimens for the treatment of T2DM.
Anti-diabetic medications and risk of pancreatic cancer in patients with diabetes mellitus: a systematic review and meta-analysis. [2018]Several preclinical and observational studies have shown that anti-diabetic medications (ADMs) may modify the risk of pancreatic cancer (PaC). We performed a systematic review and meta-analysis evaluating the effect of metformin, sulfonylureas (SUs), thiazolidinediones (TZDs), and insulin on the risk of PaC in patients with diabetes mellitus (DM).
Activation of GLP-1 receptor enhances the chemosensitivity of pancreatic cancer cells. [2022]This study aimed to determine whether and how the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide affects the chemoresistance and chemosensitivity of pancreatic cancer cells to gemcitabine in vitro and in vivo. The GLP-1R and protein kinase A (PKA) levels were compared between the human pancreatic cancer cell line PANC-1 and the gemcitabine-resistant cell line PANC-GR. The in vitro effects of liraglutide on the cell proliferation and apoptosis as well as the nuclear factor-kappa B NF-κB expression levels of PANC-GR cells were evaluated. In addition, a mouse xenograft model of human pancreatic cancer was established by s.c. injection of PANC-1 cells, and the effects of liraglutide on the chemosensitivity were evaluated in vitro and in vivo. In contrast to PANC-1 cells, PANC-GR cells exhibited lower expression levels of GLP-1R and PKA. Incubation with liraglutide dose dependently inhibited the growth, promoted the apoptosis, and increased the expression of GLP-1R and PKA of PANC-GR cells. Similar effects of liraglutide were observed in another human pancreatic cancer cell line MiaPaCa-2/MiaPaCa-2-GR. Either the GLP-1R antagonist Ex-9, the PKA inhibitor H89, or the NF-κB activator lipopolysaccharide (LPS) could abolish the antiproliferative and proapoptotic activities of liraglutide. Additionally, each of these agents could reverse the expression of NF-κB and ABCG2, which was decreased by liraglutide treatment. Furthermore, liraglutide treatment increased the chemosensitivity of pancreatic cancer cells to gemcitabine, as evidenced by in vitro and in vivo experiments. Thus, GLP-1R agonists are safe and beneficial for patients complicated with pancreatic cancer and diabetes, especially for gemcitabine-resistant pancreatic cancer.
An update on the 'gliptins'. [2017]Progressive impairment of insulin secretion in people with type 2 diabetes leads to blood glucose concentrations worsening over time, often resulting in escalation of blood glucose lowering therapy.1 In 2015/2016, more money was spent on dipeptidyl peptidase-4 (DPP-4) inhibitors ('gliptins') than on any other class of antidiabetic drug except for insulins.2 In 2008, we reviewed sitagliptin and vildagliptin.3 Here, we briefly review three other DPP-4 inhibitors, saxagliptin (Onglyza-AstraZeneca), linagliptin (Trajenta-Boehringer Ingelheim) and ▼alogliptin (Vipidia-Takeda), and consider data from recent cardiovascular outcomes studies.
Clinical pearls for initiating and utilizing liraglutide in patients with type 2 diabetes. [2015]This review presents clinical pearls for initiating liraglutide (Victoza®, Novo Nordisk Inc) therapy for the management of type 2 diabetes and selecting patients who will benefit from liraglutide therapy. Liraglutide, a once-daily glucagon-like peptide 1 receptor agonist, is Food and Drug Administration approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Liraglutide is effective for reducing hemoglobin A1c levels by 0.8% to 1.5% in patients with type 2 diabetes as monotherapy or in combination with other diabetic medications (such as metformin, sulfonylureas, rosiglitazone, or basal insulin) when compared with placebo and these other diabetic medications, including exenatide. Overweight or obese patients with type 2 diabetes or those with insulin resistance are good candidates for liraglutide therapy because liraglutide use is associated with weight loss (about 2%-4% of initial body weight) and improved β-cell function. The incidence of hypoglycemia with liraglutide is low; therefore, liraglutide would be a safe therapy choice for patients at risk or with a history of symptomatic or severe hypoglycemia. Nausea seems to be the most problematic adverse effect associated with liraglutide therapy, but it is usually transient and is minimized with dose titration.
Role of saxagliptin as monotherapy or adjunct therapy in the treatment of type 2 diabetes. [2021]Type 2 diabetes is associated with decreased incretin hormone response to an oral glucose load, and a progressive decline in postprandial glucagon-like peptide-1 (GLP-1) secretion. Incretin-based therapies offer a new option for treatment of type 2 diabetes. Saxagliptin, a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor specifically designed for extended inhibition of the DPP-4 enzyme, causes increased endogenous GLP-1 concentration. In a phase 3 clinical trials program of 24 weeks duration, saxagliptin was studied in 6 multicenter, multinational, randomized, controlled studies and in combination with 3 of the most commonly administered oral antidiabetic drugs: metformin, glyburide and a thiozolidinedione (TZD). Saxagliptin provided significant reductions in hemoglobin HbA(1c) when given with metformin, glyburide, a TZD, or as monotherapy. Saxagliptin also reduced fasting plasma glucose and 2-hour post-prandial glucose in each of these studies, and was weight and lipid neutral. Saxagliptin was well tolerated and had a low risk of hypoglycemia when used as monotherapy.
Effects of sitagliptin on 24-h glycemic changes in Japanese patients with type 2 diabetes assessed using continuous glucose monitoring. [2015]This study was performed to examine the efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes using continuous glucose monitoring (CGM) of 24-h glycemic changes.
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. [2020]Dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose co-transporter 2 (SGLT2) inhibitors improve hyperglycemia, and the usefulness of co-administration of DPP-4 inhibitors and insulin therapy has been well established. However, it has been still uncertain whether combination therapy of SGLT2 inhibitors and insulin is superior to that of DPP-4 inhibitors and the latter. Therefore, we investigated the superiority of dapagliflozin on glucose fluctuation compared with DPP-4 inhibitors in patients with type 2 diabetes mellitus (T2DM) on insulin using a continuous glucose monitoring (CGM) system.
Linagliptin and newer DPP-4 inhibitors: newer uses and newer indications. [2019]The dipeptidyl peptidase-4 (DPP-4) inhibitors linagliptin, sitagliptin, saxagliptin, vildagliptin and alogliptin are being developed and have been approved for the treatment of type-2 diabetes. These agents may be used either as monotherapy for the treatment of type-2 diabetes or in combination with other anti-diabetic drugs. The present review highlights the use of linagliptin and other new (DPP-4) inhibitors in the management of type-2 diabetes. The review also highlights advantages, comparative pharmacokinetic, safety profile and other potential uses including potential newer indications of DPP-4 inhibitors and relevant patents. The other potential uses that are not restricted to diabetes include obesity, cardiovascular disease, neurological disease, hepatobiliary disease, wound healing, and other inflammatory illnesses.