Chromogranin A as Blood Marker in Cancer Patients

NCT ID: NCT03817866

Last Updated: 2022-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

175 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-01-29

Study Completion Date

2021-12-14

Brief Summary

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Gastroentero-pancreatic neuroendocrine tumors (GEP-NETs) are a heterogenous group of neoplasms that arise from enterochromaffin cells of the gastrointestinal (GI) tract and pancreas. They account for 50-70% of all incident NETs. Due to the lack of symptoms in the early stage of disease and the frequency of nonspecific GI symptoms, GEP-NETs are difficult to diagnose.

Identification of effective biomarkers (such as Chromogranin A) to improve GEP-NET diagnosis, as well as to assess treatment efficacy, relapse and prognosis, is important for improving outcomes for patients with GEP-NETs.

The purpose of this study is to validate the performance of Brahms (BRAHMS) Chromogranin A II Kryptor (KRYPTOR) assay to monitor the course of disease in patients with well-defined GEP-NETs.

Detailed Description

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A general characteristic for neuroendocrine tumors (NET) is expression of chromogranin A (CgA), which is released from neuroendocrine cells, occasionally together with cell specific hormones such as gastrin, insulin, somatostatin, and serotonin in functional tumors. Human CgA is an acidic 439 amino acid protein with a sequence containing several mono- and dibasic cleavage sites, and correspondingly, numerous fragments of CgA have been identified in tissue and plasma. CgA is critical to the formation of secretory granules that characterize NETs, and is therefore a useful marker for NETs.

Plasma concentrations of CgA and/or CgA fragments are elevated in most NETs. Moreover, since plasma CgA concentrations seem to be closely related to tumor burden in humans, plasma CgA concentration is an important prognostic factor. As such, high plasma concentrations of CgA as well as a dramatic increase in plasma CgA within a short time period, is associated with a poorer prognosis. Plasma CgA has also been suggested to be useful in the follow-up of patients with NETs.

Taken together, these observations support the notion that CgA is a promising biomarker candidate for monitoring treatment effectiveness and disease progression or regression.

Participation in this clinical study requires no additional visits to the oncologist, radiology or the laboratory. All information needed for the study will be obtained during typical visits as recommended by the oncologist. Clinical assessment of patients with GEP-NETs (according to NCCN guidelines) is based on physical exam, imaging (CT or MRI scans) and laboratory parameters. The course of disease is followed by RECIST 1.1 categorization including the evaluation of tumor burden by imaging.

Conditions

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Gastric Neoplasms Pancreatic Neoplasms Small Intestinal Neoplasms Colorectal Neoplasms

Keywords

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Endocrine tumors Carcinoids Functional NETs Non-functional NETs Immunoassay

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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BRAHMS CgA II KRYPTOR

Adult patients with well defined grade 1 and grade 2 GEP-NETs. Serial serum samples from all patients will be analyzed using the BRAHMS CgA II KRYPTOR Assay.

BRAHMS CgA II KRYPTOR

Intervention Type DIAGNOSTIC_TEST

The BRAHMS CgA II KRYPTOR kit is an automated immunofluorescent assay for the quantitative determination of the concentration of CgA in human serum.

The assay is to be used as an aid in monitoring disease progression during the course of disease and treatment in patients with GEP-NETs (grade 1 and grade 2).

Serial testing for patient BRAHMS CgA II KRYPTOR assay values should be used in conjunction with other clinical methods for monitoring GEP-NETs (grade 1 and grade 2).

Interventions

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BRAHMS CgA II KRYPTOR

The BRAHMS CgA II KRYPTOR kit is an automated immunofluorescent assay for the quantitative determination of the concentration of CgA in human serum.

The assay is to be used as an aid in monitoring disease progression during the course of disease and treatment in patients with GEP-NETs (grade 1 and grade 2).

Serial testing for patient BRAHMS CgA II KRYPTOR assay values should be used in conjunction with other clinical methods for monitoring GEP-NETs (grade 1 and grade 2).

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Primary well-differentiated G1 and G2 neuroendocrine tumor located in jejunum, ileum, colon, rectum, duodenum, appendix, stomach, or pancreas
* Measurable disease according to RECIST criteria (Version 1.1)
* Eighteen years of age or older
* CT or MRI order obtained and within 4 weeks of CgA measurement
* BRAHMS CgA II KRYPTOR baseline measurement available
* Patient has discontinued the following treatments for at least 3 weeks before study start: i) proton pump Inhibitors (PPI), ii) corticoids, iii) H2-receptor antagonists
* Baseline Eastern Cooperative Oncology Group Performance Scale (ECOG PS) \<2
* Written informed consent signed

Exclusion Criteria

* Other active malignancy with the exclusion of melanoma or other cancers that occurred more than 5 years ago
* Participation in another clinical trial involving an investigational therapeutic (exception: diagnostic studies and studies evaluating known therapies)
* No measurable disease by RECIST criteria (Version 1.1)
* Severe renal dysfunction defined as creatinine of 1.5x upper limit of normal (ULN)
* Severe liver dysfunction in the absence of liver metastasis defined by aspartate aminotransferase (AST), serum total bilirubin and/or alanine transaminase (ALT) 1.5x ULN; severe liver dysfunction in the presence of liver metastasis defined by AST and ALT over 5x ULN and total bilirubin over 1.5x ULN
* Severe gastrointestinal disorders (chronic atrophic gastritis, pancreatitis, inflammatory bowel disease, irritable bowel syndrome)
* Severe cardiovascular disease (severe symptomatic congestive heart failure, pulmonary artery hypertension, acute coronary syndrome)
* Patients receiving active treatment with the following medications and samples were collected less than 3 weeks after discontinuing: i) proton pump Inhibitors (PPI), ii) corticoids, iii) H2-receptor antagonists
* Chronic alcohol and/or substance abuse
* Known pregnancy
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Brahms AG

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel M Halperin, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas MD Anderson Cancer Center

Locations

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Stanford University Medical Center

Palo Alto, California, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Site Status

Countries

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United States Germany

References

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Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

Reference Type RESULT
PMID: 19097774 (View on PubMed)

Related Links

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https://www.nccn.org/professionals/physician_gls/default.aspx

National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines

Other Identifiers

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Brahms-CASPAR

Identifier Type: -

Identifier Source: org_study_id