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

ConditionsCancer of EsophagusEsophagogastric Junction Disorder
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorHeinrich-Heine University, Duesseldorf

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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

Trial 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

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Not listed

Trial groups

No trial groups listed

Trial outcomes

Primary outcomes

1

Difference in CTC detection rate between peripheral and tumor draining veins.

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.

Time frame
24 months

Secondary outcomes

1

tdEVs

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.

Time frame
24 months
2

ctDNA

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.

Time frame
24 months
3

Clinical correlation

Correlation of any of the biomarker or in combination with clinical parameters and with patient clinical outcome (OS and RFS)

Time frame
84 months
4

Dynamic Biobank

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.

Time frame
24 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Heinrich-Heine University, Duesseldorf

Lead sponsor

University Hospital of Cologne

Collaborator

Source ClinicalTrials.gov
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