The Cancer of the Pancreas Screening-5 CAPS5)Study (CAPS5)

Johns Hopkins clinical research office quality assurance group will monitor and audit this study at Johns Hopkins. The Sub Investigator at each site will be responsible for internal monitoring at their site.

Study Overview

• Status: Recruiting
• Conditions: Lynch Syndrome; Pancreas Cancer; Gene Mutation; Peutz-Jeghers Syndrome (PJS); Germline Mutation Carrier
• Intervention / Treatment: Drug: Secretin; Diagnostic test: MRI; Other: Tumor marker gene test with CA19-9

Detailed Description

The Sub Investigator at each site will be responsible for internal monitoring at their site. The site sub Investigator and study team will report any serious adverse events to Principal Investigator and annually report adverse events.

• Study Type: Interventional
• Enrollment (Estimated): 7000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hilary Cosby, RN; Email: hcosby1@jhmi.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University
      • Contact: Scott Merenda, BSN; Phone Number: 203-785-7019; Email: scott.merenda@yale.edu
      • Principal Investigator: James Farrell, MD
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins Hospital
      • Contact: Hilary Cosby, RN, CGRN; Phone Number: 410-502-2893; Email: hcosby1@jhmi.edu
      • Principal Investigator: Michael Goggins, MD
      • Sub-Investigator: Marcia I Canto, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Center, Harvard University
      • Contact: Emily Blair; Phone Number: 617-632-4788; Email: emily_blair@DFCI.Harvard.edu
      • Contact: Chinedu Ukaegbu; Email: chinedu_ukaegbu@dfci.harvard.edu
      • Principal Investigator: Sapna Syngal, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Erika Koeppe, MS; Phone Number: 734-998-1274; Email: eskoeppe@med.umich.edu
      • Sub-Investigator: Elena Stoffel, MD
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Contact: Tiffany Lam; Email: tl3141@cumc.columbia.edu
      • Principal Investigator: Fay Kastrinos, MD
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • Case Comprehensive Cancer Center, Case Western Medical Reserve
      • Sub-Investigator: Amitabh Chak, MD
      • Contact: Barbara Heaton; Phone Number: 216-844-7314; Email: Barbara.Heaton@UHhospitals.org
      • Contact: Wendy Brock, RN; Phone Number: 216-844-3853; Email: wendy.Brock@UHhospitals.org
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Maureen DeMarshall, RN; Phone Number: 215-349-8546; Email: demarshm@mail.med.upenn.edu
      • Contact: Daniel Clay; Email: Daniel.Clay@Pennmedicine.upenn.edu
      • Sub-Investigator: Bryson Katona, MD
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh
      • Contact: Christine Decapite; Email: decapitec@upmc.edu
      • Principal Investigator: Randall Brand, MD
      • Contact: Sara Booz; Email: boozs@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Hereditary Pancreatitis or
• Peutz-Jeghers Syndrome or
• Strong family history of pancreas cancer on one side of the family tree or
• Confirmed germline mutation carrier (BRCA2, FAMMM, PALB2, BRCA1, HNPCC, PRSS1/2, or CTRC
• Endoscopic evaluation of pancreas scheduled

Exclusion Criteria:

• Medical comorbidities or coagulopathy that contraindicate endoscopy
• Prior surgery that prevent optimal endoscopic ultrasound such as partial or complete gastrectomy with Bilroth or Roux-en-Y anastomosis
• Stricture or obstruction in the upper GI tract that does not allow passage of the echoendoscope
• Poor performance status
• Inability to provide informed consent
• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Familial pancreas cancer relatives; High Risk Group 2 (familial pancreatic cancer relatives): > 55 years old or 10 years younger than the age of youngest relative with pancreatic cancer, and; come from a family with 2 or more members with a history of pancreatic cancer (2 of which have a first-degree relationship consistent with familial pancreatic cancer), and; have a first-degree relationship with at least one of the relatives with pancreatic cancer. If there are 2 or more affected blood relatives, at least 1 must be a first-degree relative of the individual being screened	Drug: Secretin; inject Secretin to stimulate pancreatic digestive fluid, which is collected in duodenum near ampulla via endoscope suction port. This fluid will be assessed for biomarkers.; Other Names: ChiRhoStim; Diagnostic test: MRI; MRI abdomen with contrast (MRCP) will be clinically indicated for abnormal novel CA-19-9 lab results.; Other Names: MRCP; Other: Tumor marker gene test with CA19-9; A tumor marker gene test that will be used to stratify individuals into one of several circulating tumor marker reference ranges for CA19-9. The variants in the genes FUT3 and FUT2 affect the levels of CA19-9.
Active Comparator: Group 1 germline mutation carrier; High Risk Group 3 (Group 1 germline mutation carriers with an associated with an estimated lifetime risk of pancreatic cancer of ~10% or higher): a. > 50 years old or 10 years younger than the age of the youngest relative affected, if pancreatic cancer is in family, and b. The Patient is a carrier of a confirmed BRCA2, ATM or PALB2 mutation, regardless of family history of pancreatic cancer. b.> Individual is a carrier of a confirmed FAMMM (p16/CDKN2A) mutation, age 40 years or older, regardless of family history of pancreas cancer.	Drug: Secretin; inject Secretin to stimulate pancreatic digestive fluid, which is collected in duodenum near ampulla via endoscope suction port. This fluid will be assessed for biomarkers.; Other Names: ChiRhoStim; Diagnostic test: MRI; MRI abdomen with contrast (MRCP) will be clinically indicated for abnormal novel CA-19-9 lab results.; Other Names: MRCP; Other: Tumor marker gene test with CA19-9; A tumor marker gene test that will be used to stratify individuals into one of several circulating tumor marker reference ranges for CA19-9. The variants in the genes FUT3 and FUT2 affect the levels of CA19-9.
Active Comparator: Group 2 germline mutation carrier; High Risk Group 4 (Group 2 germline mutation carriers with an associated with an estimated lifetime risk of pancreatic cancer of ~5%): > 50 years old or 10 years younger than the age of the youngest relative with pancreatic cancer, and; The patient is a carrier of a confirmed BRCA1 or HNPCC (hereditary non-polyposis colorectal cancer or Lynch syndrome, hMLH1, hMSH2, PMS1, hMSH6, EpCAM) gene mutation, and there is > 1 pancreatic cancer in the family, one of whom is a first- or second-degree relative of the subject to be screened.	Drug: Secretin; inject Secretin to stimulate pancreatic digestive fluid, which is collected in duodenum near ampulla via endoscope suction port. This fluid will be assessed for biomarkers.; Other Names: ChiRhoStim; Diagnostic test: MRI; MRI abdomen with contrast (MRCP) will be clinically indicated for abnormal novel CA-19-9 lab results.; Other Names: MRCP; Other: Tumor marker gene test with CA19-9; A tumor marker gene test that will be used to stratify individuals into one of several circulating tumor marker reference ranges for CA19-9. The variants in the genes FUT3 and FUT2 affect the levels of CA19-9.
Active Comparator: Hereditary pancreatitis; High risk group 5 (hereditary pancreatitis) with confirmed gene mutations that predispose to chronic pancreatitis, such as PRSS1, PRSS2, CTRC) and age 50 years or older (these patients have an estimated lifetime risk for pancreatic cancer of 40%) or twenty-years since their first attack of pancreatitis, whichever age is younger.	Drug: Secretin; inject Secretin to stimulate pancreatic digestive fluid, which is collected in duodenum near ampulla via endoscope suction port. This fluid will be assessed for biomarkers.; Other Names: ChiRhoStim; Diagnostic test: MRI; MRI abdomen with contrast (MRCP) will be clinically indicated for abnormal novel CA-19-9 lab results.; Other Names: MRCP; Other: Tumor marker gene test with CA19-9; A tumor marker gene test that will be used to stratify individuals into one of several circulating tumor marker reference ranges for CA19-9. The variants in the genes FUT3 and FUT2 affect the levels of CA19-9.
Active Comparator: Peutz-Jeghers Syndrome; At least 30 years old, and; at least 2 of 3 criteria diagnostic of Peutz-Jeghers syndrome (characteristic intestinal hamartomatous polyps, mucocutaneous melanin deposition, or family history of Peutz-Jeghers syndrome), or,; known STK11 gene mutation carrier	Drug: Secretin; inject Secretin to stimulate pancreatic digestive fluid, which is collected in duodenum near ampulla via endoscope suction port. This fluid will be assessed for biomarkers.; Other Names: ChiRhoStim; Diagnostic test: MRI; MRI abdomen with contrast (MRCP) will be clinically indicated for abnormal novel CA-19-9 lab results.; Other Names: MRCP; Other: Tumor marker gene test with CA19-9; A tumor marker gene test that will be used to stratify individuals into one of several circulating tumor marker reference ranges for CA19-9. The variants in the genes FUT3 and FUT2 affect the levels of CA19-9.
Active Comparator: Negative control; are undergoing routine EGD or Colonoscopy; or Endoscopic Ultrasound (EUS) and/or Endoscopic Retrograde Cholangiopancreatography (ERCP) for non-pancreatic indications as part of their standard medical care, and; have no clinical or radiologic suspicion of pancreatic disease (chronic pancreatitis or pancreatic cancer)	Drug: Secretin; inject Secretin to stimulate pancreatic digestive fluid, which is collected in duodenum near ampulla via endoscope suction port. This fluid will be assessed for biomarkers.; Other Names: ChiRhoStim
Active Comparator: Chronic Pancreatitis; are undergoing EUS and/or ERCP for evaluation and/or treatment of suspected or proven chronic pancreatitis as part of their standard medical care, and,; have no clinical or radiologic suspicion of pancreatic cancer	Drug: Secretin; inject Secretin to stimulate pancreatic digestive fluid, which is collected in duodenum near ampulla via endoscope suction port. This fluid will be assessed for biomarkers.; Other Names: ChiRhoStim
Active Comparator: Pancreas cancer; a. are undergoing EUS and/or ERCP for evaluation and/or treatment of suspected or proven pancreatic ductal adenocarcinoma (based on clinical and radiologic evidence)	Drug: Secretin; inject Secretin to stimulate pancreatic digestive fluid, which is collected in duodenum near ampulla via endoscope suction port. This fluid will be assessed for biomarkers.; Other Names: ChiRhoStim
Active Comparator: Pancreas cyst, IPMN evaluation; are undergoing EUS and/or ERCP for evaluation and/or treatment of suspected or proven pancreatic cancer precursor, intraductal papillary mucinous neoplasm (based on clinical presentation and radiologic or prior EUS or radiologic evidence of a dilated main pancreatic duct and/or pancreatic cystic lesion communicating with the pancreatic ductal system).	Drug: Secretin; inject Secretin to stimulate pancreatic digestive fluid, which is collected in duodenum near ampulla via endoscope suction port. This fluid will be assessed for biomarkers.; Other Names: ChiRhoStim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate pancreatic juice for early cancer markers.	Aim #1: To evaluate pancreatic fluid mutations and circulating pancreatic epithelial cells as accurate markers of neoplasia by comparing their prevalence in cases with sporadic pancreatic neoplasia to healthy and disease controls.	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare pancreas juice with pancreas cyst fluid	Aim #2: To compare the prevalence of pancreatic fluid mutations and circulating pancreatic epithelial cells among a prospective cohort of individuals with sporadic pancreatic cysts undergoing pancreatic surveillance.	10 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time disease progression and prevalence	Aim #3: To determine the prevalence of pancreatic lesions, pancreatic fluid mutations and circulating pancreatic epithelial cells among a large cohort of high-risk individuals undergoing pancreatic screening and surveillance of a new cohort in which screening is begun at age >55.	10 years
Diagnostic performance of a tumor marker gene test for CA19-9 interpretation	Aim #4 To evaluate the diagnostic performance of a tumor marker gene test to personalize the normal reference range of tumor markers such as CA19-9 for patients undergoing pancreatic surveillance.	5 years

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH); ChiRhoClin, Inc.
• Investigators: Principal Investigator: Michael Goggins, MD, Johns Hopkins University

Publications and helpful links

General Publications

• Kumar S, Saumoy M, Oh A, Schneider Y, Brand RE, Chak A, Ginsberg GG, Kochman ML, Canto MI, Goggins MG, Hur C, Kastrinos F, Katona BW, Rustgi AK. Threshold Analysis of the Cost-effectiveness of Endoscopic Ultrasound in Patients at High Risk for Pancreatic Ductal Adenocarcinoma. Pancreas. 2021 Jul 1;50(6):807-814. doi: 10.1097/MPA.0000000000001835.
• Kohi S, Macgregor-Das A, Dbouk M, Yoshida T, Chuidian M, Abe T, Borges M, Lennon AM, Shin EJ, Canto MI, Goggins M. Alterations in the Duodenal Fluid Microbiome of Patients With Pancreatic Cancer. Clin Gastroenterol Hepatol. 2022 Feb;20(2):e196-e227. doi: 10.1016/j.cgh.2020.11.006. Epub 2020 Nov 5.
• Abe T, Koi C, Kohi S, Song KB, Tamura K, Macgregor-Das A, Kitaoka N, Chuidian M, Ford M, Dbouk M, Borges M, He J, Burkhart R, Wolfgang CL, Klein AP, Eshleman JR, Hruban RH, Canto MI, Goggins M. Gene Variants That Affect Levels of Circulating Tumor Markers Increase Identification of Patients With Pancreatic Cancer. Clin Gastroenterol Hepatol. 2020 May;18(5):1161-1169.e5. doi: 10.1016/j.cgh.2019.10.036. Epub 2019 Oct 30.
• Canto MI, Kerdsirichairat T, Yeo CJ, Hruban RH, Shin EJ, Almario JA, Blackford A, Ford M, Klein AP, Javed AA, Lennon AM, Zaheer A, Kamel IR, Fishman EK, Burkhart R, He J, Makary M, Weiss MJ, Schulick RD, Goggins MG, Wolfgang CL. Surgical Outcomes After Pancreatic Resection of Screening-Detected Lesions in Individuals at High Risk for Developing Pancreatic Cancer. J Gastrointest Surg. 2020 May;24(5):1101-1110. doi: 10.1007/s11605-019-04230-z. Epub 2019 Jun 13.

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2014
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 26, 2013
• First Submitted That Met QC Criteria: November 26, 2013
• First Posted (Estimated): December 3, 2013

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Lynch Syndrome; familial pancreas cancer; (Peutz-Jeghers Syndrome) PJS; Breast cancer (BRCA) 2; Partner and Locator of BRCA2 (PALB2); Familial Atypical Multiple Mole- Melanoma (FAMMM); p16, CDKN2A; Breast Cancer (BRCA)1; (hereditary non-polyposis colorectal cancer or Lynch syndrome) HNPCC; hereditary pancreatitis; Protease Serine (PRSS); Chymotrypsin C (CTRC); Ataxia Telangiectasia Mutated(ATM)
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Metabolic Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Disease; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Genetic Diseases, Inborn; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Neoplastic Syndromes, Hereditary; DNA Repair-Deficiency Disorders; Pancreatic Diseases; Intestinal Polyposis; Hyperpigmentation; Pigmentation Disorders; Melanosis; Lentigo; Syndrome; Colorectal Neoplasms, Hereditary Nonpolyposis; Pancreatic Neoplasms; Peutz-Jeghers Syndrome; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Secretin
• Other Study ID Numbers: NA_00087754; 1U01CA210170-01 (U.S. NIH Grant/Contract); R01CA176828 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No