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

NCT ID: NCT04455282

Last Updated: 2024-03-08

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-02-01
• Study Completion Date: 2028-01-30

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).

Conditions

Cancer of Esophagus; Esophagogastric Junction Disorder

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital of Cologne

OTHER

Sponsor Role: collaborator

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: lead

Responsible Party

Univ.-Prof. Dr. med. Nikolas H. Stoecklein

Head of Experimental Surgical Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nikolas Stoecklein, MD

Role: PRINCIPAL_INVESTIGATOR

Surgery, University Hospital Düsseldorf Germany

Christiane Bruns, MD

Role: PRINCIPAL_INVESTIGATOR

Surgery, University Hospital Cologne

Locations

University Hospital Cologne

Cologne, North Rhine-Westphalia, Germany

Site Status: RECRUITING

Universitätsklinikum Münster

Münster, North-Rhine Westfalia, Germany

Site Status: NOT_YET_RECRUITING

Countries

Germany

Central Contacts

Nikolas H Stoecklein, MD

Role: CONTACT

Nikolas.Stoecklein@med.uni-duesseldorf.de

004921181 ext. 16399

Christiane Bruns, MD

Role: CONTACT

christiane.bruns@uk-koeln.de

Facility Contacts

Christiane Bruns, MD

Role: primary

christiane.bruns@uk-koeln.de

+49 221 47 ext. 84801

Raphael Stier, MD

Role: backup

raphael.stier@uk-koeln.de

+49 221 47 ext. 84801

Mazen A Juratli, MD, PhD

Role: primary

mazen.juratli@ukmuenster.de

+49 251 8356304

References

de Wit S, Rossi E, Weber S, Tamminga M, Manicone M, Swennenhuis JF, Groothuis-Oudshoorn CGM, Vidotto R, Facchinetti A, Zeune LL, Schuuring E, Zamarchi R, Hiltermann TJN, Speicher MR, Heitzer E, Terstappen LWMM, Groen HJM. Single tube liquid biopsy for advanced non-small cell lung cancer. Int J Cancer. 2019 Jun 15;144(12):3127-3137. doi: 10.1002/ijc.32056. Epub 2019 Jan 28.

Reference Type: BACKGROUND

PMID: 30536653 (View on PubMed)

Belic J, Koch M, Ulz P, Auer M, Gerhalter T, Mohan S, Fischereder K, Petru E, Bauernhofer T, Geigl JB, Speicher MR, Heitzer E. Rapid Identification of Plasma DNA Samples with Increased ctDNA Levels by a Modified FAST-SeqS Approach. Clin Chem. 2015 Jun;61(6):838-49. doi: 10.1373/clinchem.2014.234286. Epub 2015 Apr 20.

Reference Type: BACKGROUND

PMID: 25896989 (View on PubMed)

Reeh M, Effenberger KE, Koenig AM, Riethdorf S, Eichstadt D, Vettorazzi E, Uzunoglu FG, Vashist YK, Izbicki JR, Pantel K, Bockhorn M. Circulating Tumor Cells as a Biomarker for Preoperative Prognostic Staging in Patients With Esophageal Cancer. Ann Surg. 2015 Jun;261(6):1124-30. doi: 10.1097/SLA.0000000000001130.

Reference Type: BACKGROUND

PMID: 25607767 (View on PubMed)

Pernot S, Badoual C, Terme M, Castan F, Cazes A, Bouche O, Bennouna J, Francois E, Ghiringhelli F, De La Fouchardiere C, Samalin E, Bachet JB, Borg C, Ducreux M, Marcheteau E, Stanbury T, Gourgou S, Malka D, Taieb J. Dynamic evaluation of circulating tumour cells in patients with advanced gastric and oesogastric junction adenocarcinoma: Prognostic value and early assessment of therapeutic effects. Eur J Cancer. 2017 Jul;79:15-22. doi: 10.1016/j.ejca.2017.03.036. Epub 2017 Apr 26.

Reference Type: BACKGROUND

PMID: 28456090 (View on PubMed)

Buscail E, Chiche L, Laurent C, Vendrely V, Denost Q, Denis J, Thumerel M, Lacorte JM, Bedel A, Moreau-Gaudry F, Dabernat S, Alix-Panabieres C. Tumor-proximal liquid biopsy to improve diagnostic and prognostic performances of circulating tumor cells. Mol Oncol. 2019 Sep;13(9):1811-1826. doi: 10.1002/1878-0261.12534. Epub 2019 Jul 25.

Reference Type: BACKGROUND

PMID: 31216108 (View on PubMed)

Other Identifiers

2020-06-BS

Identifier Type: -

Identifier Source: org_study_id