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CIRCULATing Biomarkers for Individualized Surgical Therapy in gastroEsophageal Cancer - Phase 1 (CIRCULATE1)

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ClinicalTrials.gov Identifier: NCT04455282
Recruitment Status : Recruiting
First Posted : July 2, 2020
Last Update Posted : March 8, 2024
Sponsor:
Collaborator:
University Hospital of Cologne
Information provided by (Responsible Party):
Univ.-Prof. Dr. med. Nikolas H. Stoecklein, Heinrich-Heine University, Duesseldorf

Study Description
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Brief Summary:
This is an exploratory observational biomarker study in approximately 100 eligible patients with resectable adenocarcinomas of the esophagus and gastro- esophageal junction (GEJ) type I-II (GEAC) to investigate the difference deletion frequency of circulating tumor cells (CTCs) between peripheral veins and tumor-draining veins (primary endpoint), prognostic value, relevance of a set of two additional blood-based biomarkers analyzed from a single blood sampling tube (secondary endpoints). The underlying hypothesis is that the biomarker alone or in combination improve preoperative staging and help to identify patients at risk for metastasis. This should enable a better stratification of GEAC patients to neo-adjuvant treatment, (intensified) peri-operative treatment, or even surgery alone, in selected cases. The data of the CIRCULATE study shall be used design subsequent studies testing the predictive role of these biomarkers for surgical management. Patients will provide blood samples and lymphatic fluid during the operation and annual blood samples during clinical follow up of 5 years.

Condition or disease
Cancer of Esophagus Esophagogastric Junction Disorder

Detailed Description:
This is an exploratory observational biomarker study. Around 20 mL of blood will be collected from a peripheral vein and additional 40 mL from tumor draining veins. In addition, around 5 mL of lymphatic fluid will be collected from the thoracic duct, when exposed and opened during the surgical resection. Annual blood draws (20 mL) will be performed during routine clinical follow-up or at the time point when the patients develops a (metastatic) relapse. A one tube protocol will be performed from each blood sample to assess CTCs and tumor derived extracellular Vesicles (tdEVs) using CELLSEARCH® and ACCEPT (https://github.com/LeonieZ/ACCEPT/blob/master/ACCEPT.m). In addition, tumor cells will be enumerated by CELLSEARCH® in the lymphatic fluid. ctDNA will be extracted from plasma of each blood collection tube and analyzed by mFAST-SeqS. If the mutational status of the primary tumor is known, deep sequencing of ctDNA will be applied for mutation tracking at a later time point. Tissue resected during the surgical procedure and not required for routine pathology will be collected into a biobank (cry-conserved and formalin fixed and paraffin embedded (FFPE).
Study Design
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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: CIRCULATing Biomarkers for Individualized Surgical Therapy in gastroEsophageal Cancer - Phase 1
Actual Study Start Date : February 1, 2021
Estimated Primary Completion Date : December 30, 2024
Estimated Study Completion Date : January 30, 2028

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Outcome Measures
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Primary Outcome Measures :
  1. Difference in CTC detection rate between peripheral and tumor draining veins. [ Time Frame: 24 months ]
    The difference between the CTC positivity rate (≥1 CTC / 7.5 mL) in blood samples of tumor-draining veins compared to the CTC positivity rate in peripheral blood. The positivity fraction and CTC number per 7.5 mL in tumor draining veins and peripheral blood samples will be determined by CellSearch.


Secondary Outcome Measures :
  1. tdEVs [ Time Frame: 24 months ]
    1. The tdEV number per 7.5 mL determined from CellSearch images using the ACCEPT software tool and the fraction of tdEVs positive patients (a cut-off threshold will be applied)(de Wit, 2019). 2. The difference between tdEV measurement in the tumor-draining veins and the peripheral blood will be assessed.

  2. ctDNA [ Time Frame: 24 months ]
    1. The tumor allele frequency measured by the genome-wide mFAST-SeqS assay (Belic, 2015) and the fraction of patients with high tumor allele frequency will be determined. For this, a threshold of 10% tumour allele frequency will be applied to discriminate high allele frequency (>10%) from low allele frequency (≤10%) cases (Belic, 2015; de Wit, 2019). 2. The difference between ctDNA measurement in the tumor-draining veins and the peripheral blood will be assessed.

  3. Clinical correlation [ Time Frame: 84 months ]
    Correlation of any of the biomarker or in combination with clinical parameters and with patient clinical outcome (OS and RFS)

  4. Dynamic Biobank [ Time Frame: 24 months ]
    The number of tumor tissues (primary tumor, lymph node metastasis, biopsy material), isolated CELLSEARCH® CTCs and plasma/ctDNA samples generated from CIRCULATE1 and stored in the respective biobanks from the University Hospital of Cologne and from University Hospital Düsseldorf.


Biospecimen Retention:   Samples With DNA
blood, tumor material

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
The targeted study population of CIRCULATE1 are 100 patients (see 2.3) with resectable GEAC (GEJ type I-II) undergoing surgery with curative intention. The patients will be recruited and screened consecutively by trained surgeons involved into the CIRCULATE study. Patients are recruited to participate in this study at the outpatient clinic
Criteria

Inclusion Criteria:

  • histologically proven adenocarcinoma of the GEJ type I and II, resectable, non-metastatic tumor
  • age ≥18
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2,
  • American Society of Anesthesiologists (ASA) < 4.
  • pre-treatment stage cT1N+ M0 or cT2-4a N0/N+, M0 GEJ type I and II adenocarcinomas can be included. In case of stage cT4a, curative resectability has to be explicitly verified by the local surgical investigator prior inclusion.
  • Written informed consent and the ability to understand the nature of the study and the study-related procedures and to comply with them has to be ensured.

Exclusion Criteria:

  • tumors of squamous, adenosquamous or other non-adenocarcinoma histology
  • patients with inoperable or metastatic GEJ type I and II adenocarcinoma, GEJ type I and II adenocarcinoma staged cT1N0 and cT4b, GEJ type I and II cT4a evaluated as not curatively resectable by the local surgical investigator
  • unsigned informed consent
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04455282


Contacts
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Contact: Nikolas H Stoecklein, MD 004921181 ext 16399 Nikolas.Stoecklein@med.uni-duesseldorf.de
Contact: Christiane Bruns, MD christiane.bruns@uk-koeln.de

Locations
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Germany
Universitätsklinikum Münster Not yet recruiting
Münster, North-Rhine Westfalia, Germany, 48149
Contact: Mazen A Juratli, MD, PhD    +49 251 8356304    mazen.juratli@ukmuenster.de   
University Hospital Cologne Recruiting
Cologne, NRW, Germany
Contact: Christiane Bruns, MD    +49 221 47 ext 84801    christiane.bruns@uk-koeln.de   
Contact: Raphael Stier, MD    +49 221 47 ext 84801    raphael.stier@uk-koeln.de   
Sponsors and Collaborators
Heinrich-Heine University, Duesseldorf
University Hospital of Cologne
Investigators
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Principal Investigator: Nikolas Stoecklein, MD Surgery, University Hospital Düsseldorf Germany
Principal Investigator: Christiane Bruns, MD Surgery, University Hospital Cologne
More Information
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Publications:

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Responsible Party: Univ.-Prof. Dr. med. Nikolas H. Stoecklein, Head of Experimental Surgical Oncology, Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier: NCT04455282    
Other Study ID Numbers: 2020-06-BS
First Posted: July 2, 2020    Key Record Dates
Last Update Posted: March 8, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Univ.-Prof. Dr. med. Nikolas H. Stoecklein, Heinrich-Heine University, Duesseldorf:
Circulating Biomarkers
CTC
tdEVs
ctDNA
Additional relevant MeSH terms:
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Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
 Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases