Glipizide for High Blood Sugar in Pancreatic Cancer

Recruiting at 6 trial locations

Overseen By Eileen O'Reilly, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Metformin, Sulfonylureas

Must not be taking: Corticosteroids

Disqualifiers: Severe hypoglycemia, Liver issues, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out how effective and safe glipizide is for lowering blood sugar in people with pancreatic cancer.

Will I have to stop taking my current medications?

The trial requires that participants in Cohort 1 stop using any antidiabetic medication other than metformin for at least a month before joining. If you're in Cohort 2a or 2b, the protocol does not specify stopping current medications, but you should discuss your specific situation with the trial team.

How does the drug Glipizide differ from other treatments for high blood sugar in pancreatic cancer?

Glipizide is unique because it is primarily used to lower blood sugar in people with type 2 diabetes by stimulating the pancreas to release more insulin. Its use in pancreatic cancer patients with high blood sugar is novel, as there are no standard treatments specifically targeting blood sugar control in this condition. ^{1 2 3 4 5}

Research Team

James Flory, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with metastatic pancreatic cancer and high blood sugar levels, who haven't had certain diabetes treatments or surgeries like Whipple surgery. They should be able to use a mobile device with Bluetooth and follow the study's protocol. People are excluded if they have a history of severe hypoglycemia, certain liver issues, very low kidney function, significant fluid in the abdomen, or daily steroid use.

Inclusion Criteria

Cohort 1: Age ≥18 years, Biopsy-proven PDAC, Radiological evidence and clinical assessment that disease is metastatic, Willing and able to comply with the requirements of the protocol, Willing to use their bluetooth-enabled wifi or cellular mobile device, Hemoglobin A1c (HbA1c) >8%, fructosamine >325 mg/dL, random glucose >200 mg/dL, or strong clinical suspicion that patient has hyperglycemia, making it reasonable to expect their mean daily glucose is ≥183 mg/dL, Eastern Cooperative Oncology Group performance status ≤2, BMI <30 kg/m2

Cohort 2a: Age ≥18 years, Biopsy-proven PDAC, Radiological evidence and clinical assessment that disease is metastatic, Active care at MSK (defined as at least 1 physician or APP encounter every 3 months) for PDAC during the period from which data were recorded in the electronic medical record (in this retrospective study patients need not be under active care at the time the research is conducted), At least 1 electronic prescription for a sulfonylurea (glipizide, glimepiride, or glyburide) or metformin, Three-month baseline period before metformin or sulfonylurea initiation in which the participant does not receive either drug class or insulin, Body weight recorded within 3 months before start of metformin or a sulfonylurea

Cohort 2b: Age ≥18 years, Biopsy-proven PDAC, Radiological evidence and clinical assessment that disease is metastatic, Active care at MSK (defined as at least 1 physician or APP encounter every 3 months) for PDAC during the period of data collection, Apparent current use based on chart review of metformin (but not sulfonylurea); sulfonylurea (but not metformin); or neither drug

Exclusion Criteria

Cohort 1: History of distal pancreatectomy or of Whipple surgery, History of diabetes diagnosed 2 years or more prior to pancreas cancer diagnosis, Use during the past month of any antidiabetic medication at home (sporadic insulin use [fewer than 1 of 7 days during the past month] is permitted), History of sulfonylurea intolerance or allergy, History of severe hypoglycemia (hypoglycemia requiring emergency medical assistance, emergency room or urgent care visit, or hospital admission), AST or ALT >3 x upper limit of normal, Glomerular filtration rate <30 mL/min/1.73m2, Greater than trace ascites documented on imaging or physical exam, Daily chronic use of any dose of corticosteroids (as distinct from intermittent exposure to steroids as part of cyclic chemotherapy), Inability to wear CGM

I have had surgery on my pancreas and have more than a small amount of fluid in my abdomen.

I have had surgery on my pancreas and have more than a small amount of fluid in my abdomen.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants in Cohort 1 receive glipizide for up to 4 months and participate in continuous glucose monitoring

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Glipizide

Trial Overview The trial is testing how well Glipizide can lower blood sugar in people with advanced pancreatic cancer. It aims to determine both the effectiveness and safety of this medication specifically for these patients.

Participant Groups

Group I: Cohort 1 Experimental Treatment 1 Intervention

Participants in this cohort will receive glipizide for up to 4 months and participate in continuous glucose monitoring for as long as they are receiving the drug.

Group II: Cohort 2a Active Control 1 Intervention

Participants in this cohort will include people who have received various types of treatment for their hyperglycemia and pancreatic cancer. People's medical records will be reviewed to compare the effects of glipizide with the effects of other standard medications used to treat hyperglycemia.

Group III: Cohort 2b Active Control 1 Intervention

Participants in this cohort will complete a questionnaire about their use of hyperglycemia medications. Participants from Cohort 2a will take part in this group.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

In a study of 123 patients with localized pancreatic cancer, those with elevated preoperative HbA1c levels (greater than 6.5%) were less likely to complete their planned neoadjuvant therapy and surgery, indicating a potential barrier to effective treatment.

Abnormal preoperative HbA1c levels were also associated with a nearly threefold increase in the odds of metastatic progression during neoadjuvant therapy, suggesting that glycemic control may play a critical role in the management of pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poor Glycemic Control Is Associated with Failure to Complete Neoadjuvant Therapy and Surgery in Patients with Localized Pancreatic Cancer. Rajamanickam, ES., Christians, KK., Aldakkak, M., et al.[2022]

A meta-analysis of 21 studies involving 38,772 patients found that metformin treatment is associated with a significant survival benefit in pancreatic cancer patients with diabetes, showing a hazard ratio of 0.83 compared to those not using metformin.

The survival benefit of metformin was particularly notable in early-stage pancreatic cancer patients and those undergoing surgery or comprehensive treatment, but not in advanced stages or among those receiving chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationships are between metformin use and survival in pancreatic cancer patients concurrent with diabetes: A systematic review and meta-analysis. Shi, YQ., Zhou, XC., Du, P., et al.[2022]

In a study involving Syrian golden hamsters, the administration of streptozotocin (STZ) diabetes after exposure to the pancreatic carcinogen BOP did not affect the incidence of pancreatic cancer, suggesting that STZ diabetes established post-carcinogen exposure does not influence cancer development.

This research indicates that while STZ diabetes can inhibit pancreatic cancer development when given before carcinogen exposure, it does not have the same effect when administered after, highlighting the timing of diabetes onset in relation to cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of streptozotocin diabetes on development of nitrosamine-induced pancreatic carcinoma when diabetes induction occurs after nitrosamine exposure. Povoski, SP., Fenoglio-Preiser, CM., Sayers, HJ., et al.[2019]

In a study of 101 patients who underwent partial pancreatectomy for cancer, only 20% developed new onset diabetes post-surgery, suggesting that the incidence of diabetes after such procedures is relatively low.

Interestingly, 34% of patients with preexisting diabetes experienced improved glycemic control or were cured after surgery, indicating that despite the loss of islet cell mass, some patients may benefit in terms of diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of pancreatic cancer and subsequent resection on glycemic control in diabetic and nondiabetic patients. White, MA., Agle, SC., Fuhr, HM., et al.[2022]

In a study using Syrian hamsters, inducing diabetes with streptozotocin significantly reduced the incidence of pancreatic cancer from 75% in nondiabetic controls to 24% in diabetic animals, suggesting that diabetes may inhibit the development of pancreatic carcinoma.

Blocking diabetes with nicotinamide restored the cancer incidence to levels seen in nondiabetic controls, indicating that the effects of diabetes on cancer susceptibility are reversible and closely linked to the severity of the diabetic condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of diabetes on susceptibility to experimental pancreatic cancer. Bell, RH., McCullough, PJ., Pour, PM.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Poor Glycemic Control Is Associated with Failure to Complete Neoadjuvant Therapy and Surgery in Patients with Localized Pancreatic Cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Relationships are between metformin use and survival in pancreatic cancer patients concurrent with diabetes: A systematic review and meta-analysis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Effect of streptozotocin diabetes on development of nitrosamine-induced pancreatic carcinoma when diabetes induction occurs after nitrosamine exposure. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Impact of pancreatic cancer and subsequent resection on glycemic control in diabetic and nondiabetic patients. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Influence of diabetes on susceptibility to experimental pancreatic cancer. [2019]