Pancreatic Cancer Screening for Pancreatic Cancer

(CAPS5 Trial)

Recruiting at7 trial locations

Overseen by Michael Goggins, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Johns Hopkins University

Disqualifiers: Coagulopathy, Prior surgery, Pregnancy, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is overseen by Johns Hopkins clinical research office. Team members at each location will report any major issues to the lead researcher.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment CA19-9 for pancreatic cancer screening?

CA19-9 is the most commonly used biomarker for diagnosing pancreatic cancer in symptomatic patients and monitoring therapy, although it has limitations such as false negatives and positives. It is currently the best validated serum tumor marker for pancreatic cancer, despite not being a perfect screening tool. ^{1 2 3 4 5}

Is the CA19-9 test safe for humans?

The CA19-9 test, used as a marker for pancreatic cancer, is generally safe for humans as it involves measuring a substance in the blood. However, it is not always accurate, as it can give false positive or negative results, especially in people with certain genetic traits. ^{1 2 3 4 6}

How does this treatment for pancreatic cancer differ from other treatments?

This treatment is unique because it focuses on using glycan-based biomarkers, specifically sialyl-Lewis A (sLeA) and sialyl-Lewis X (sLeX), to improve the detection and classification of pancreatic cancers. Unlike the standard CA19-9 biomarker, which is not elevated in about 25% of pancreatic cancer cases, this approach can identify additional cancer cases by detecting related glycans, potentially leading to more accurate diagnosis. ^{1 2 7 8 9}

Research Team

Michael Goggins, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for individuals with a scheduled endoscopic evaluation of the pancreas, who either have Hereditary Pancreatitis, Peutz-Jeghers Syndrome, a strong family history of pancreatic cancer, or specific genetic mutations. It's not suitable for those with upper GI tract obstructions, inability to consent, conditions that make endoscopy risky, certain prior surgeries like gastrectomy or if pregnant.

Inclusion Criteria

I have a genetic condition or a strong family history of pancreatic cancer.

I am scheduled for a pancreas examination using an endoscope.

Exclusion Criteria

My health severely limits my daily activities.

I have a blockage in my upper digestive tract that prevents certain medical procedures.

Pregnancy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pancreatic Surveillance

Participants undergo pancreatic screening and surveillance, including evaluation of pancreatic fluid mutations and circulating pancreatic epithelial cells.

10 years

Follow-up

Participants are monitored for safety and effectiveness after initial screening and surveillance activities.

5 years

Treatment Details

Interventions

• CA19-9 (Diagnostic Test)
• Human Synthetic Secretin (Drug)
• MRI (Diagnostic Test)
• Secretin (Drug)

Trial Overview The CAPS5 Study is testing the effectiveness of secretin and tumor marker gene tests (including CA19-9) alongside MRI in detecting pancreatic cancer in high-risk groups. The study will be monitored by Johns Hopkins' quality assurance group and sub-investigators at each site.

Participant Groups

Group I: Group 1 germline mutation carrier Active Control 3 Interventions

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.

Group II: Peutz-Jeghers Syndrome Active Control 3 Interventions

1. At least 30 years old, and 2. 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, 3. known STK11 gene mutation carrier

Group III: Negative control Active Control 1 Intervention

1. 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 2. have no clinical or radiologic suspicion of pancreatic disease (chronic pancreatitis or pancreatic cancer)

Group IV: Pancreas cyst, IPMN evaluation Active Control 1 Intervention

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).

Group V: Chronic Pancreatitis Active Control 1 Intervention

1. 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, 2. have no clinical or radiologic suspicion of pancreatic cancer

Group VI: Hereditary pancreatitis Active Control 3 Interventions

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.

Group VII: Familial pancreas cancer relatives Active Control 3 Interventions

High Risk Group 2 (familial pancreatic cancer relatives): 1. \> 55 years old or 10 years younger than the age of youngest relative with pancreatic cancer, and 2. 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 3. 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

Group VIII: Pancreas cancer Active Control 1 Intervention

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)

Group IX: Group 2 germline mutation carrier Active Control 3 Interventions

High Risk Group 4 (Group 2 germline mutation carriers with an associated with an estimated lifetime risk of pancreatic cancer of \~5%): 1. \> 50 years old or 10 years younger than the age of the youngest relative with pancreatic cancer, and 2. 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.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

ChiRhoClin, Inc.

Industry Sponsor

Trials

10

Recruited

9,900+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Dr. Jeanne Marrazzo

National Institutes of Health (NIH)

Chief Medical Officer

MD from University of California, Los Angeles

Dr. Jay Bhattacharya

National Institutes of Health (NIH)

Chief Executive Officer

MD, PhD from Stanford University

Findings from Research

CA19-9 is the most validated serum tumor marker for diagnosing pancreatic cancer and monitoring treatment, but it has limitations such as false negatives in individuals with the Lewis (a-b-) genotype and false positives in benign conditions.

Despite the emergence of many potential biomarkers for pancreatic cancer, none have proven to be as effective as CA19-9, which remains the only clinically used marker despite its moderate positive predictive value of 72.3%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CA 19-9: Biochemical and Clinical Aspects. Scarà, S., Bottoni, P., Scatena, R.[2022]

A new panel of glycan biomarkers, including sialyl-Lewis X and a sialylated form of type 1 N-acetyl-lactosamine, shows improved diagnostic accuracy for pancreatic cancer compared to the traditional CA19-9 antigen, achieving 85% sensitivity and 90% specificity in a study of 200 subjects.

This new biomarker panel outperforms CA19-9, which has a sensitivity of only 54% and a specificity of 86%, highlighting its potential for better early detection of pancreatic cancer in distinct patient subsets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycans related to the CA19-9 antigen are elevated in distinct subsets of pancreatic cancers and improve diagnostic accuracy over CA19-9. Tang, H., Partyka, K., Hsueh, P., et al.[2019]

Lewis-negative pancreatic cancer patients (5-10% of individuals) have a poorer prognosis, with higher metastatic rates and lower CA19-9 expression compared to Lewis-positive patients, based on a study of 853 patients.

Molecular analysis revealed that Lewis-negative cancer cells exhibit higher proliferation and migration rates, along with distinct morphological features, indicating they represent a more aggressive form of pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lewis antigen‑negative pancreatic cancer: An aggressive subgroup. Liu, C., Deng, S., Jin, K., et al.[2021]

In a study involving 578 pancreatic cancer patients, 210 with benign pancreatic disease, and 315 normal subjects, using Lewis and Secretor genotype-dependent cut-off values significantly improved the sensitivity of CA19-9 for detecting pancreatic cancer from 80.1% to 88.0%.

The optimized CA19-9 detection method also enhanced the sensitivity for early-stage pancreatic cancer (stage I and II) from 76.1% to 87.2%, indicating that adjusting cut-off values based on genetic factors can improve early detection of this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimize CA19-9 in detecting pancreatic cancer by Lewis and Secretor genotyping. Luo, G., Guo, M., Jin, K., et al.[2018]

A new glycoprotein antigen associated with pancreatic cancer was identified, showing elevated levels in patients with pancreatic cancer compared to those with other diseases and normal subjects, indicating its potential as a diagnostic marker.

The assay developed for this antigen, utilizing both monoclonal antibodies and specific lectins, could enhance the accuracy of pancreatic cancer diagnosis by targeting unique cancer-associated glycoconjugates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation of pancreatic cancer-associated mucin expressing CA19-9, CA50, Span-1, sialyl SSEA-1, and Dupan-2. Kawa, S., Kato, M., Oguchi, H., et al.[2019]

The study identified the CA 19-9 ganglioside antigen in tumors from 16 pancreatic cancer patients, confirming it as a sialyl Lewis(a) ganglioside through mass spectrometry.

There was a significant correlation between serum CA 19-9 levels and the presence of the ganglioside antigen in tumors, suggesting that serum levels may reflect tumor characteristics rather than overall tumor burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sialyl Lewis(a) ganglioside in pancreatic cancer tissue correlates with the serum CA 19-9 level. Hamanaka, Y., Hamanaka, S., Suzuki, M.[2019]

The study highlights that different CA 19-9 antibodies have varying specificities, which can significantly impact their effectiveness in detecting pancreatic cancer, as shown through antibody arrays comparing samples from cancer patients and controls.

One antibody was found to bind not only to the canonical CA 19-9 epitope but also to a related structure, sialyl-Lewis C, allowing for better detection of cancer patients without increasing false positives from pancreatitis cases, suggesting that antibody specificity is crucial for improving cancer biomarker performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diverse monoclonal antibodies against the CA 19-9 antigen show variation in binding specificity with consequences for clinical interpretation. Partyka, K., Maupin, KA., Brand, RE., et al.[2021]

CA19-9 is a key biomarker for pancreatic cancer with about 80% sensitivity, but its effectiveness can be limited by false positives in inflammatory conditions and false negatives in individuals lacking the Lewis antigen, highlighting the need for careful interpretation in clinical settings.

Beyond its role as a biomarker, CA19-9 can promote cancer progression through mechanisms like enhancing angiogenesis and immune response, making it a promising target for therapeutic strategies such as antibodies, vaccines, and nanoparticles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Roles of CA19-9 in pancreatic cancer: Biomarker, predictor and promoter. Luo, G., Jin, K., Deng, S., et al.[2023]

The study identified that sialyl-Lewis X (sLeX), a structural isomer of the current pancreatic cancer biomarker sialyl-Lewis A (sLeA), is elevated in the plasma of some pancreatic cancers that do not show elevated sLeA levels, potentially improving early diagnosis.

A two-marker panel combining sLeA and sLeX detection achieved 79% accuracy in differentiating pancreatic cancers from benign diseases, outperforming sLeA alone, which had 68% accuracy, suggesting that glycan-based biomarkers could enhance clinical diagnosis of pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycan motif profiling reveals plasma sialyl-lewis x elevations in pancreatic cancers that are negative for sialyl-lewis A. Tang, H., Singh, S., Partyka, K., et al.[2021]

References

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

CA 19-9: Biochemical and Clinical Aspects. [2022]

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

Glycans related to the CA19-9 antigen are elevated in distinct subsets of pancreatic cancers and improve diagnostic accuracy over CA19-9. [2019]

3. Greece pubmed.ncbi.nlm.nih.gov

Lewis antigen‑negative pancreatic cancer: An aggressive subgroup. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Optimize CA19-9 in detecting pancreatic cancer by Lewis and Secretor genotyping. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Preparation of pancreatic cancer-associated mucin expressing CA19-9, CA50, Span-1, sialyl SSEA-1, and Dupan-2. [2019]

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

Sialyl Lewis(a) ganglioside in pancreatic cancer tissue correlates with the serum CA 19-9 level. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Diverse monoclonal antibodies against the CA 19-9 antigen show variation in binding specificity with consequences for clinical interpretation. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Roles of CA19-9 in pancreatic cancer: Biomarker, predictor and promoter. [2023]

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

Glycan motif profiling reveals plasma sialyl-lewis x elevations in pancreatic cancers that are negative for sialyl-lewis A. [2021]