Rectal Cancer CTC Trial

NCT07194616 | Recruiting

• 1 other identifier: RECTA-CTC
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 4

Brief Summary

This prospective, multi-centre, randomised clinical trial aims to compare the effect of neoadjuvant chemoradiotherapy versus primary surgery on circulating tumor cells (CTCs) in patients with stage II-III rectal cancer without circumferential resection mar-gin involvement. CTCs are considered a promising biomarker for disease dissemination and treatment response. Patients will be randomized to either primary surgical resection with total mesorectal excision or long-course neoadjuvant chemoradiotherapy followed by surgery. Serial blood samples will be collected at predefined time points to assess the presence and dynamics of CTCs. Secondary endpoints include perioperative morbidity and mortality, local recurrence rate, disease-free survival, and overall survival. The results of this study may provide new insights into the prognostic role of CTCs and contribute to optimising treatment strategies for rectal cancer.

Conditions

Rectal Cancer Patients

Keywords

circulating tumor cells; liquid biopsy; neoadjuvant chemoradiotherapy; prognostic biomarkers; rectal cancer; surgical resection

Outcome Measures

Primary Outcomes (10)

• Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - shape

  The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of CTC round shape will be observed.

  (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively

• Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - size

  The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The CTC size will be observed, with the border value of \> 4 μm.

  (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively

• Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - DAPI positivity

  The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The DAPI positivity will be observed. A DAPI-positive nucleus is a cell nucleus that has been stained with DAPI (4',6-diamidino-2-phenylindole), a fluorescent dye that binds specifically to the adenine-thymine (A-T) rich regions of double-stranded DNA.

  (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively

• Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - pancytokeratin and/or EpCAM positivity

  The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of pancytokeratin and/or EpCAM positivity in CTCs will be observed. EpCAM positivity refers to the presence of EpCAM (Epithelial Cell Adhesion Molecule) protein on cells, which is a marker primarily expressed on epithelial cells and in many carcinomas.

  (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively

• Circulating Tumor Cells (CTC) Dynamics - neoadjuvant treatment - CD45 negativity

  The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of CD45 negativity in CTCs will be observed. "CD45 negative" means a cell does not express the CD45 protein on its surface.

  (1) before the initiation of CRT, (2) 1 week and (3) 1 month after the initiation of CRT, (4) preoperatively (1-2 weeks before surgery), (5) 1 week postoperatively, and (6) 1 month postoperatively

• Circulating Tumor Cells (CTC) Dynamics - primary surgery - shape

  The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of CTC round shape will be observed.

  (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively

• Circulating Tumor Cells (CTC) Dynamics - primary surgery - size

  The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The CTC size will be observed, with the border value of \> 4 μm.

  (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively

• Circulating Tumor Cells (CTC) Dynamics - primary surgery - DAPI positivity

  The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The DAPI positivity will be observed. A DAPI-positive nucleus is a cell nucleus that has been stained with DAPI (4',6-diamidino-2-phenylindole), a fluorescent dye that binds specifically to the adenine-thymine (A-T) rich regions of double-stranded DNA.

  (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively

• Circulating Tumor Cells (CTC) Dynamics - primary surgery - pancytokeratin and/or EpCAM positivity

  The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of pancytokeratin and/or EpCAM positivity in CTCs will be observed. EpCAM positivity refers to the presence of EpCAM (Epithelial Cell Adhesion Molecule) protein on cells, which is a marker primarily expressed on epithelial cells and in many carcinomas.

  (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively

• Circulating Tumor Cells (CTC) Dynamics - primary surgery - CD45 negativity

  The detection of CTC in laboratory will be performed using fluorescence microscope. Potential CTC candidates (hotspots) were identified based on green fluorescence and subjected to operator review. The presence of CD45 negativity in CTCs will be observed. "CD45 negative" means a cell does not express the CD45 protein on its surface.

  (1) preoperatively (1-2 weeks before surgery), (2) 1 week postoperatively, and (3) 1 month postoperatively

Secondary Outcomes (6)

• Short-term postoperative outcomes - preoperative complications

  Within 30 days after surgery

• Short-term postoperative outcomes - 30-day morbidity

  Within 30 days after surgery

• Short-term postoperative outcomes - 30-day mortality

  Within 30 days after surgery

• Local recurrence rate

  Up to 5 years

• Disease-free survival (DFS)

  3 and 5 years after surgery

Study Arms (2)

Primary Surgery

EXPERIMENTAL

Procedure: rectal resection with TME (Total Mesorectal Excision)

Procedure: Primary Surgery

Neoadjuvant radiochemotherapy and surgery

EXPERIMENTAL

Procedure: rectal resection with TME performed 6-10 weeks after completion of chemoradiotherapy.

Procedure: Neoadjuvant radiochemotherapy and surgery

Interventions

Primary Surgery PROCEDURE

Patients undergo radical surgical resection with TME without preceding neoadjuvant therapy

Primary Surgery

Neoadjuvant radiochemotherapy and surgery PROCEDURE

Neoadjuvant treatment: long-course pelvic radiotherapy (conventional fractionation) with concurrent chemotherapy (standard fluoropyrimidine-based regimen)

Neoadjuvant radiochemotherapy and surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Histologically confirmed rectal adenocarcinoma within 12 cm from anal verge
• Stage II (cT3-4 N0 M0) or stage III (cT1-4 N1-2, M0)
• Negative circumferential resection margin on staging MRI
• ASA physical status I-III
• Signed informed consent

You may not qualify if:

• Tumor infiltration beyond fascia recti propria on MRI
• Metastatic disease (stage IV)
• Recurrent rectal cancer
• Other concurrent malignancies
• Emergency surgery required
• Contraindication to surgery under general anesthesia

Sponsors & Collaborators

• University Hospital Ostrava: lead
• Palacky University: collaborator
• University Hospital Olomouc: collaborator
• Municipal Hospital Ostrava: collaborator

Study Sites (4)

University Hospital Olomouc

Olomouc, 779 00, Czechia

RECRUITING

Palacky University Olomouc, Faculty of Medicine

Olomouc, Czechia

RECRUITING

University Hospital Ostrava

Ostrava, 70852, Czechia

RECRUITING

Municipal Hospital Ostrava - Fifejdy

Ostrava, 728 80, Czechia

RECRUITING

Related Publications (18)

• Lu CY, Uen YH, Tsai HL, Chuang SC, Hou MF, Wu DC, Juo SH, Lin SR, Wang JY. Molecular detection of persistent postoperative circulating tumour cells in stages II and III colon cancer patients via multiple blood sampling: prognostic significance of detection for early relapse. Br J Cancer. 2011 Mar 29;104(7):1178-84. doi: 10.1038/bjc.2011.40. Epub 2011 Feb 22.

  PMID: 21343933 BACKGROUND

• Hinz S, Roder C, Tepel J, Hendricks A, Schafmayer C, Becker T, Kalthoff H. Cytokeratin 20 positive circulating tumor cells are a marker for response after neoadjuvant chemoradiation but not for prognosis in patients with rectal cancer. BMC Cancer. 2015 Dec 16;15:953. doi: 10.1186/s12885-015-1989-z.

  PMID: 26674974 BACKGROUND

• Yadav A, Kumar A, Siddiqui MH. Detection of circulating tumour cells in colorectal cancer: Emerging techniques and clinical implications. World J Clin Oncol. 2021 Dec 24;12(12):1169-1181. doi: 10.5306/wjco.v12.i12.1169.

  PMID: 35070736 BACKGROUND

• Burz C, Pop VV, Buiga R, Daniel S, Samasca G, Aldea C, Lupan I. Circulating tumor cells in clinical research and monitoring patients with colorectal cancer. Oncotarget. 2018 May 11;9(36):24561-24571. doi: 10.18632/oncotarget.25337. eCollection 2018 May 11.

  PMID: 29849961 BACKGROUND

• Wu J, Li Z, Zou J, Li L, Cui N, Hao T, Yi K, Yang J, Wu Y. A meta-analysis of the value of circulating tumor cells in monitoring postoperative recurrence and metastasis of colorectal cancer. PLoS One. 2022 Sep 19;17(9):e0274282. doi: 10.1371/journal.pone.0274282. eCollection 2022.

  PMID: 36121855 BACKGROUND

• Sun W, Li G, Wan J, Zhu J, Shen W, Zhang Z. Circulating tumor cells: A promising marker of predicting tumor response in rectal cancer patients receiving neoadjuvant chemo-radiation therapy. Oncotarget. 2016 Oct 25;7(43):69507-69517. doi: 10.18632/oncotarget.10875.

  PMID: 27486758 BACKGROUND

• Pan RJ, Hong HJ, Sun J, Yu CR, Liu HS, Li PY, Zheng MH. Detection and Clinical Value of Circulating Tumor Cells as an Assisted Prognostic Marker in Colorectal Cancer Patients. Cancer Manag Res. 2021 Jun 8;13:4567-4578. doi: 10.2147/CMAR.S300554. eCollection 2021.

  PMID: 34135633 BACKGROUND

• Tseng M, Soon YY, Vellayappan B, Ho F, Tey J. Radiation therapy for rectal cancer. J Gastrointest Oncol. 2019 Dec;10(6):1238-1250. doi: 10.21037/jgo.2018.12.04.

  PMID: 31949945 BACKGROUND

• Uen YH, Lu CY, Tsai HL, Yu FJ, Huang MY, Cheng TL, Lin SR, Wang JY. Persistent presence of postoperative circulating tumor cells is a poor prognostic factor for patients with stage I-III colorectal cancer after curative resection. Ann Surg Oncol. 2008 Aug;15(8):2120-8. doi: 10.1245/s10434-008-9961-7. Epub 2008 May 15.

  PMID: 18481151 BACKGROUND

• Kulu Y, Tarantino I, Billeter AT, Diener MK, Schmidt T, Buchler MW, Ulrich A. Comparative Outcomes of Neoadjuvant Treatment Prior to Total Mesorectal Excision and Total Mesorectal Excision Alone in Selected Stage II/III Low and Mid Rectal Cancer. Ann Surg Oncol. 2016 Jan;23(1):106-13. doi: 10.1245/s10434-015-4832-5. Epub 2015 Aug 25.

  PMID: 26305025 BACKGROUND

• Rahbari NN, Elbers H, Askoxylakis V, Motschall E, Bork U, Buchler MW, Weitz J, Koch M. Neoadjuvant radiotherapy for rectal cancer: meta-analysis of randomized controlled trials. Ann Surg Oncol. 2013 Dec;20(13):4169-82. doi: 10.1245/s10434-013-3198-9. Epub 2013 Sep 4.

  PMID: 24002536 BACKGROUND

• Ihnat P, Zidlik V, Ihnat Rudinska L, Koscielnik P, Hanzlikova P, Skarda J. Magnetic resonance imaging in preoperative assessment of the mesorectal nodal status of patients with rectal cancer - Can it be trusted? Eur J Radiol. 2023 Aug;165:110961. doi: 10.1016/j.ejrad.2023.110961. Epub 2023 Jul 5.

  PMID: 37423017 BACKGROUND

• Sauer R, Fietkau R, Wittekind C, Rodel C, Martus P, Hohenberger W, Tschmelitsch J, Sabitzer H, Karstens JH, Becker H, Hess C, Raab R; German Rectal Cancer Group. Adjuvant vs. neoadjuvant radiochemotherapy for locally advanced rectal cancer: the German trial CAO/ARO/AIO-94. Colorectal Dis. 2003 Sep;5(5):406-15. doi: 10.1046/j.1463-1318.2003.00509.x.

  PMID: 12925071 BACKGROUND

• Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20. doi: 10.1016/S0140-6736(09)60484-0.

  PMID: 19269519 BACKGROUND

• van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011 Jun;12(6):575-82. doi: 10.1016/S1470-2045(11)70097-3. Epub 2011 May 17.

  PMID: 21596621 BACKGROUND

• Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rodel C, Cervantes A, Arnold D; ESMO Guidelines Committee. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1;29(Suppl 4):iv263. doi: 10.1093/annonc/mdy161. No abstract available.

  PMID: 29741565 BACKGROUND

• van de Velde CJ, Boelens PG, Tanis PJ, Espin E, Mroczkowski P, Naredi P, Pahlman L, Ortiz H, Rutten HJ, Breugom AJ, Smith JJ, Wibe A, Wiggers T, Valentini V. Experts reviews of the multidisciplinary consensus conference colon and rectal cancer 2012: science, opinions and experiences from the experts of surgery. Eur J Surg Oncol. 2014 Apr;40(4):454-68. doi: 10.1016/j.ejso.2013.10.013. Epub 2013 Nov 8.

  PMID: 24268926 BACKGROUND

• Ihnat P, Srovnal J, Stejskal P, Vidlarova M, Skacelikova E, Snajder B, Varga A, Ihnat Rudinska L. Monitoring Treatment Response in Rectal Cancer through Circulating Tumor Cell Dynamics: A Pilot Clinical Study. J Surg Oncol. 2025 Nov;132(6):1052-1057. doi: 10.1002/jso.70073. Epub 2025 Sep 2.

  PMID: 40891187 BACKGROUND

MeSH Terms

Conditions

Neoplastic Cells, Circulating; Rectal Neoplasms

Interventions

Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Peter Ihnát, prof., MD, PhD, MBA

  University Hospital Ostrava

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiří Hynčica

CONTACT

0042059737; jiri.hyncica@fno.cz

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2025
• First Posted: September 26, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): March 30, 2028
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (4)