Early Detection Initiative for Pancreatic Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Hyperglycemia, Diabetes Mellitus, Pancreas Ductal Adenocarcinoma

Intervention / Treatment
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* Other: Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) score
* Other: Abdominal imaging


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial with post-randomization consent
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Arm<br>Two interventions are performed: Have Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) score calculated, and if Score is >0, Have abdominal imaging performed. | Other: Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) score<br>* 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.<br>Other: Abdominal imaging<br>* 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.<br>|
| No Intervention: Observation Arm<br>Passive follow-up by electronic medical record for study endpoints of pancreatic cancer diagnosis. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Validate ENDPAC model | Prospectively validate the ENDPAC model. | Baseline and approximately every six months for up to five years | 
| 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 | 
| 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 | 
| 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 | 
| Depression and Anxiety as early indicators | Determine if symptoms of depression and anxiety are early indicators of PDAC. | Baseline and follow-up visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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New Onset Diabetes, Hyperglycemia, Diabetes Mellitus, Pancreatic Ductal Adenocarcinoma, ENDPAC score, Weight loss