Skip to main content
OpenTrials
Recruiting

NCT Number: NCT04455282

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Cancer of Esophagus Digestive System Diseases Digestive System Neoplasms Esophageal Diseases Esophageal Neoplasms Esophagogastric Junction Disorder Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Neoplasms Neoplasms Neoplasms by Site

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University Hospital Cologne, Cologne, North Rhine-Westphalia, Germany

Loading trial locations.

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  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 outcomes

  1. tdEVs

    Time frame: 24 months

    • 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

    • 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Christiane Bruns, MD

CONTACT

[email protected]

Nikolas H Stoecklein, MD

CONTACT

[email protected]

004921181 ext. 16399

Sponsors and collaborators

Lead sponsor

Heinrich-Heine University, Duesseldorf

Other

Collaborators

  • University Hospital of Cologne

Registry information

Acronym: CIRCULATE1

Important dates

Study start
2021
Primary completion
2024
Study completion
2028
First posted
Jul 2, 2020
Registry last updated
Mar 8, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.