Clinical trial NCT04455282: CIRCULATing Biomarkers for Individualized Surgical Therapy in gastroEsophageal Cancer - Phase 1
Official title: CIRCULATing Biomarkers for Individualized Surgical Therapy in gastroEsophageal Cancer - Phase 1
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cancer of Esophagus
Esophagogastric Junction Disorder
Keywords: Circulating Biomarkers
CTC
tdEVs
ctDNA
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
Collaborators: name: University Hospital of Cologne
First posted: 2020-07-02
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

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).

Eligibility 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

Primary outcomes:
measure: Difference in CTC detection rate between peripheral and tumor draining veins.
timeFrame: 24 months
Secondary outcomes:
measure: tdEVs
timeFrame: 24 months
measure: ctDNA
timeFrame: 24 months
measure: Clinical correlation
timeFrame: 84 months
measure: Dynamic Biobank
timeFrame: 24 months
Other outcomes:
Locations:
city: Münster
country: Germany
facility: Universitätsklinikum Münster
state: North-Rhine Westfalia
city: Cologne
country: Germany
facility: University Hospital Cologne
state: NRW
Study officials:
affiliation: Surgery, University Hospital Düsseldorf Germany
name: Nikolas Stoecklein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Surgery, University Hospital Cologne
name: Christiane Bruns, MD
role: PRINCIPAL_INVESTIGATOR
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