Clinical trial NCT04662879: Early Detection Initiative for Pancreatic Cancer
Official title: A Prospective Study of Algorithm-based Screening in Patients With Glycemically Defined New Onset Diabetes to Evaluate Risk for and Earlier Detection of Pancreatic Ductal Adenocarcinoma; Early Detection Initiative (EDI) for Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hyperglycemia
Diabetes Mellitus
Pancreas Ductal Adenocarcinoma
Keywords: New Onset Diabetes
Hyperglycemia
Diabetes Mellitus
Pancreatic Ductal Adenocarcinoma
ENDPAC score
Weight loss
Glycemically defined new onset diabetes
Lead sponsor: Pancreatic Cancer Action Network
Sponsor class: OTHER
First posted: 2020-12-10
Enrollment: 8869
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Post-enrollment consent
Primary purpose: SCREENING

Brief summary: The Early Detection Initiative for Pancreatic Cancer is a multi-center prospective study to determine if algorithm-based screening in patients with glycemically defined new onset hyperglycemia and diabetes has the potential for earlier detection of pancreatic ductal adenocarcinoma.

Detailed description: The Early Detection Initiative (EDI), is designed to prospectively evaluate the performance characteristics of the Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) model to enrich glycemically defined new-onset diabetes for pancreatic cancer. The study will also determine with elevated ENDPAC score occurs at a clinically meaningful lead time (\>/= 4 months) before pancreatic cancer diagnosis.

Eligible patients are identified and enrolled based on a first-time elevation in fasting blood glucose parameters or glycated hemoglobin (HbA1c) to the level indicating glycemically defined new-onset diabetes as derived from records in their EMR. At sites performing the Intervention component of the study, all enrolled participants will have the 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 a study questionnaire. At sites that do not perform the Intervention component of the study, participants will be identified, enrolled, and followed by EMR data only. All enrolled participants 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 three years following enrollment. Any patient that has declined participation in EMR-based research at the institution is not included in the study.

Eligibility criteria: 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 (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.
* For Intervention Sites, patients must meet inclusion criteria A, B, or C ≤90 days prior to enrollment.

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 ongoing active treatment for cancer, and/or carry a current diagnosis of any cancer (except non-melanoma skin cancer). Non-invasive cancer of any organ (carcinoma-in-situ/high grade dysplasia) is not an exclusion.

  \*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.
* Patient must have values available in the EMR to calculate the ENDPAC score.

Primary outcomes:
measure: Validate the ENDPAC model
timeFrame: Baseline and approximately every six months for up to three years
measure: Quantify potentially clinically meaningful lead time for earlier detection of PDAC
timeFrame: Baseline and approximately every six months for up to three years
Secondary outcomes:
measure: Evaluate the risk of PDAC in G-NOD
timeFrame: Baseline and approximately every six months for up to three years
measure: Proportion of incidental findings on imaging
timeFrame: Baseline and imaging follow-up visit, up to 9 months
measure: Risk of PDAC by subgroups
timeFrame: Baseline and approximately every six months for up to three years
measure: Reasons consent for intervention was declined
timeFrame: Baseline and approximately every six months for up to five years
Other outcomes:
measure: Stage of disease at PDAC diagnosis
timeFrame: Baseline and approximately every six months for up to three years
measure: Glycemic parameters for ENDPAC model
timeFrame: Baseline and approximately every six months for up to three years
measure: ENDPAC model by subgroups
timeFrame: Baseline and approximately every six months for up to three years
measure: Depression and Anxiety as early indicators
timeFrame: Baseline visit
Locations:
city: Pasadena
country: United States
facility: Kaiser Permanente Southern California, Kaiser Permanente Research
state: California
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Suresh Chari, MD
role: STUDY_CHAIR
affiliation: M.D. Anderson Cancer Center
name: Anirban Maitra, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaiser Permanente
name: Bechien Wu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Avinash Kambadakone-Ramesh, MD, FRCR
role: PRINCIPAL_INVESTIGATOR
affiliation: Fred Hutchinson Cancer Center
name: Ziding Feng, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
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.
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.
citation: Chari ST, Maitra A, Matrisian LM, Shrader EE, Wu BU, Kambadakone A, Zhao YQ, Kenner B, Rinaudo JAS, Srivastava S, Huang Y, Feng Z; Early Detection Initiative Consortium. Early Detection Initiative: A randomized controlled trial of algorithm-based screening in patients with new onset hyperglycemia and diabetes for early detection of pancreatic ductal adenocarcinoma. Contemp Clin Trials. 2022 Feb;113:106659. doi: 10.1016/j.cct.2021.106659. Epub 2021 Dec 23.