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

Обзор

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.

Подробное описание

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).

Первичные конечные точки

• Difference in CTC detection rate between peripheral and tumor draining veins. [Срок оценки: 24 months]

Вторичные конечные точки (4)

• tdEVs [Срок оценки: 24 months]
• ctDNA [Срок оценки: 24 months]
• Clinical correlation [Срок оценки: 84 months]
• Dynamic Biobank [Срок оценки: 24 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Германия · 2 центра

• University Hospital Cologne — Cologne
• Universitätsklinikum Münster — Münster

Публикации

• 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. PMID 30536653
• 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. PMID 25896989
• 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. PMID 25607767
• 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. PMID 28456090
• 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. PMID 31216108

Идентификаторы

NCT: NCT04455282 · 2020-06-BS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗