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Cancer of EsophagusCIRCULATE1NCT04455282

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

An observational study of Cancer of Esophagus and Esophagogastric Junction Disorder, run by Heinrich-Heine University, Duesseldorf at 2 sites in Germany.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
How many people
100 participants
Where
2 sitesGermany
Study dates
1 Feb 2021to 30 Jan 2028
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Who may be able to join

  • 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.

Who cannot join

  • 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 locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Nikolas H Stoecklein, MD contact

004921181 ext. 16399

Nikolas.Stoecklein@med.uni-duesseldorf.de

Christiane Bruns, MD contact

christiane.bruns@uk-koeln.de

Germany2 sites, 2 recruiting

  • University Hospital Cologne

    Cologne, North Rhine-Westphalia

    Christiane Bruns, MD, +49 221 47 ext. 84801, christiane.bruns@uk-koeln.de

    Raphael Stier, MD, +49 221 47 ext. 84801, raphael.stier@uk-koeln.de

    Recruiting

  • Universitätsklinikum Münster

    Münster, North-Rhine Westfalia, 48149

    Mazen A Juratli, MD, PhD, +49 251 8356304, mazen.juratli@ukmuenster.de

    Not yet recruiting

Other trials in Germany

About this study

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.

Read the 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).

Keywords
Circulating Biomarkers, CTC, tdEVs, ctDNA
Medical subject headings
Esophageal Neoplasms

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 24 months

Secondary outcomes (4)

  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.

    Measured: 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.

    Measured: 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)

    Measured: 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.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2020
  2. Study start1 Feb 2021
  3. Primary completion30 Dec 2024 (estimated)
  4. Study completion30 Jan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04455282
Sponsor's protocol ID
2020-06-BS
Acronym
CIRCULATE1
Status last verified
Mar 2024
First submitted
29 Jun 2020
Last updated
8 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 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.

    PubMed 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.

    PubMed 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. Eur J Cancer. 2017 Jul;79:15-22. doi: 10.1016/j.ejca.2017.03.036. Epub 2017 Apr 26.

    PubMed 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.

    PubMed 31216108

Questions about this trial

What is this clinical trial studying?

An observational study of Cancer of Esophagus and Esophagogastric Junction Disorder, run by Heinrich-Heine University, Duesseldorf at 2 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Nikolas H Stoecklein, MD (004921181 ext. 16399, Nikolas.Stoecklein@med.uni-duesseldorf.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Difference in CTC detection rate between peripheral and tumor draining veins. (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04455282, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2024.

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