Early Detection Initiative for Pancreatic Cancer

Diabetes Mellitus Clinical Trial

— EDI  

Official title:

A Randomized Controlled Trial of Algorithm-based Screening in Patients With New Onset Hyperglycemia and Diabetes for Early Detection of Pancreatic Ductal Adenocarcinoma (Early Detection Initiative (EDI) for Pancreatic Cancer)

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04662879
• Other study ID #: 466
• Secondary ID: FHIRB0010533RG10
• Status: Enrolling by invitation
• Phase: N/A
• Start date: October 14, 2021
• Est. completion date: July 2030

Study information

• Verified date: July 2023
• Source: Pancreatic Cancer Action Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The Early Detection Initiative for Pancreatic Cancer is a multi-center randomized controlled trial to determine if algorithm-based screening in patients with new onset hyperglycemia and diabetes can result in earlier detection of pancreatic ductal adenocarcinoma.

Description:

The Early Detection Initiative (EDI), is designed to evaluate if imaging at the time of new onset hyperglycemia and diabetes, especially at its earliest discovery through passive surveillance of the electronic medical record (EMR), results in earlier detection of pancreatic ductal adenocarcinoma (PDAC).

Eligible patients are identified and enrolled based on a first-time elevation in fasting blood glucose or glycated hemoglobin (HbA1c) to the level indicating diabetes as derived from records in their EMR. All enrolled patients are randomized to either the Observational Arm or Intervention Arm of the study. Patients randomized to the Intervention Arm have Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) score calculated using age, body weight and glucose or glycated hemoglobin values in their EMR. Patients with high ENDPAC score (>0) are approached for informed consent to participate in up to two imaging studies by computerized tomography (CT) scan or magnetic resonance imaging (MRI). In addition to imaging, participants will be asked to complete study questionnaires and participate in serial blood collection at up to five time points. Blood samples collected in the EDI study will contribute to the National Institutes of Health (NIH) National Cancer Institute (NCI) biorepository located at the Frederick National Laboratory for Cancer Research facility. Patients in both study arms are followed for development of PDAC.

This study is performed at locations with broad (institutional) consent for use of patient EMR information for research studies. Passive follow-up by EMR will occur for five years following enrollment. Any patient that has declined participation in EMR-based research at the institution is not included in the study.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 12500
• Est. completion date: July 2030
• Est. primary completion date: July 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

Inclusion Criteria:

• Patient must have given institutional consent for minimal risk studies.

• Patient must be =50 and =85 years of age at the time of diagnosis [index date Parameters of Diabetes Mellitus (PDM)].

• Patient must have index weight and left-window weight values available in electronic medical record (EMR).

• Patient must have hyperglycemia and/or diabetes as one of the following =90 days prior to randomization (all glycemic parameters, except for HbA1c, must be measured in an outpatient setting):

A. Glycated hemoglobin (HbA1c) = 6.5%

OR

B. Any (2) PDMs on consecutive (=90 days between PDMs) or simultaneous testing:

• Fasting Blood Glucose (FBG) =126 mg/dl

• Glycated hemoglobin (HbA1c) = 6.5%

• Random Blood Glucose (RBG) =200 mg/dl

• 2 hour Post Glucose (PG) = 200mg (11.1 mmol/L) during oral glucose tolerance test (OGTT)

OR

C. Any one (1) PDM present followed by an anti- diabetes medication =90 days after the index PDM date

• Patient must have =1 glycemic parameter measured in the past 91-548 days prior to the index PDM date (Left Window) without meeting inclusion criteria A, B, or C.

Exclusion Criteria:

• Patient has declined institutional consent for minimal risk studies.

• Patient must not have any known past history of hyperglycemia and/or diabetes as defined by inclusion criteria A, B, or C

*Transient diabetes (e.g. gestational and steroid-induced) is not an exclusion.

• Patient must not be on active treatment for cancer, carry a current diagnosis of any cancer, and/or investigated for suspicion of recurrence of past cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix).

*Ongoing work up for suspicion of pancreatic cancer is not an exclusion.

• Patient must not have had a definitive diagnosis of pancreatic cancer prior to index PDM date.

• Patient must not be on any anti-diabetes medications prior to index PDM date.

• Patient must not be on chronic or acute use of steroid medications =90 days prior to the index PDM date.

*Allowed: Nasal, topical steroids, oral budesonide, ophthalmic

• Patient must not have had an intra-articular steroid injection = 7 days prior to the index PDM date.

Related Conditions & MeSH terms

• Adenocarcinoma
• Diabetes Mellitus
• Hyperglycemia
• Pancreas Ductal Adenocarcinoma

Intervention

Other:
• Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) score
ENDPAC is a model to risk-stratify patients with new onset diabetes and hyperglycemia for PDAC. Score is calculated using i) age, ii) change, over past year, in body weight and iii) change, over past year, in glucose/HbA1c values obtained from the electronic medical record.
• Abdominal imaging
Using computerized tomography (CT) scan or magnetic resonance imaging (MRI), if CT scan is contra-indicated, patients with a high ENDPAC score (>0) are approached for informed consent to participate in the imaging intervention. Imaging (CT scan) is performed at up to two time points, study baseline and approximately 3-9 months following the first imaging study.

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas
United States	Kaiser Permanente Southern California, Kaiser Permanente Research	Pasadena	California

Sponsors (3)

Lead Sponsor	Collaborator
Pancreatic Cancer Action Network	Fred Hutchinson Cancer Center, National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Chari ST, Leibson CL, Rabe KG, Ransom J, de Andrade M, Petersen GM. Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology. 2005 Aug;129(2):504-11. doi: 10.1016/j.gastro.2005.05.007. — View Citation

Chen W, Butler RK, Lustigova E, Chari ST, Wu BU. Validation of the Enriching New-Onset Diabetes for Pancreatic Cancer Model in a Diverse and Integrated Healthcare Setting. Dig Dis Sci. 2021 Jan;66(1):78-87. doi: 10.1007/s10620-020-06139-z. Epub 2020 Feb 28. — View Citation

Khan S, Safarudin RF, Kupec JT. Validation of the ENDPAC model: Identifying new-onset diabetics at risk of pancreatic cancer. Pancreatology. 2021 Apr;21(3):550-555. doi: 10.1016/j.pan.2021.02.001. Epub 2021 Feb 8. — View Citation

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. — View Citation

Sharma A, Smyrk TC, Levy MJ, Topazian MA, Chari ST. Fasting Blood Glucose Levels Provide Estimate of Duration and Progression of Pancreatic Cancer Before Diagnosis. Gastroenterology. 2018 Aug;155(2):490-500.e2. doi: 10.1053/j.gastro.2018.04.025. Epub 2018 Apr 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Earlier detection of pancreatic ductal adenocarcinoma (PDAC)	Determine if algorithm-based screening in new onset hyperglycemia and diabetes (NOD) results in earlier detection of pancreatic ductal adenocarcinoma (PDAC) as evidenced by a lower proportion of Stage III/IV disease at the time of PDAC diagnosis in intervention vs observation arm.	Baseline and approximately every six months for up to five years
Secondary	Smaller proportion of unresectable disease	Determine if Intervention results in earlier detection of PDAC defined as a smaller proportion of unresectable disease.	Baseline and approximately every six months for up to five years
Secondary	Less Stage IV disease	Determine if Intervention results in earlier detection of PDAC defined as less Stage IV disease.	Baseline and approximately every six months for up to five years
Secondary	Smaller proportion with advanced pancreatic cancer symptoms	Determine if Intervention results in earlier detection of PDAC defined as a smaller proportion with advanced pancreatic cancer symptoms.	Baseline and approximately every six months for up to five years
Secondary	Estimating risk in subgroups	Estimate the risk of PDAC in NOD and Enriching New-onset Diabetes (or hyperglycemia) for Pancreatic Cancer (ENDPAC) subgroups.	Baseline and approximately every six months for up to five years
Secondary	Validate ENDPAC model	Prospectively validate the ENDPAC model.	Baseline and approximately every six months for up to five years
Secondary	Over diagnosis due to imaging intervention of NOD	Determine the magnitude of over diagnosis due to imaging intervention of NOD.	Baseline and imaging follow-up visit, up to 9 months
Secondary	Determine the proportion of incidental findings	Determine, on imaging in NOD, the proportion with incidental findings that require clinical workup.	Baseline and approximately every six months for up to five years
Secondary	Contribute to NOD biobank	Contribute blood biospecimens to a previously established NOD cohort biobank for future biomarker validation studies.	Baseline and blood collection follow-up visits, up to 36 months
Secondary	Depression and Anxiety as early indicators	Determine if symptoms of depression and anxiety are early indicators of PDAC.	Baseline and follow-up visits

External Links

•   Pancreatic Cancer Action Network Early Detection Initiative