Role of Circulating Tumour DNA Testing in Assessing for Alterations of Primary Anti-EGFR Resistance in RAS/RAF Wild-type Metastatic Colorectal Cancer Patients

NCT05051592 | Unknown

• 1 other identifier: 2020/00339
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to explore the clinical utility of circulating tumour DNA (ctDNA) in assessing for alterations of anti-epidermal growth factor receptor (EGFR) primary resistance in RAS and BRAF wild-type metastatic colorectal cancer (CRC) patients treated with anti-EGFR monoclonal antibodies (cetuximab / panitumumab) in combination with fluorouracil (FU)-doublet chemotherapy.

Conditions

Colorectal Cancer

Keywords

ctDNA; anti_EGFR; RAS/RAF wild-type metastatic colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Detection rate of alterations of anti-epidermal growth factor receptor primary resistance using Circulating tumour DNA

  ctDNA analysis will be carried out using Guardant360 platform to identify subgroup of patients who have primary resistance to anti-EGFR therapy.

  One timepoint, within 4 weeks prior to starting of anti-EGFR therapy

Secondary Outcomes (4)

• Response rate

  1 year 6 months

• Progression-free survival

  1 year 6 months

• Overall survival

  1 year 6 months

• Adverse reactions experience by patient

  1 year 6 months

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with newly diagnosed RAS/BRAF wild-type mCRC who are beginning standard-of-care treatment with fluorouracil-based doublet chemotherapy in combination with anti-EGFR monoclonal antibodies will be recruited into the study. These are patients who are cared for at the National University Cancer Institute, Singapore (NCIS), and identified through the colorectal surgery, medical oncology and multidisciplinary CRC tumour board at NCIS.

You may qualify if:

• Patients with newly diagnosed stage IV colon or rectal cancer who are RAS/BRAF wild-type by routine tumor profiling and who are beginning standard-of-care treatment with fluorouracil-based doublet chemotherapy in combination with anti-EGFR monoclonal antibodies. Prior treatment with adjuvant therapy is allowed if completed more than 6 months prior to relapse of disease.

You may not qualify if:

• Pregnant women will be excluded from the study.
• Patient unable to give informed consent will be excluded from the study.
• Patients who have previously received chemotherapy in the metastatic setting.
• Patients who have previously received adjuvant chemotherapy less than 6 months prior to relapse of metastatic disease.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

RECRUITING

Related Publications (8)

• Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Kohne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Osterlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taieb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016 Aug;27(8):1386-422. doi: 10.1093/annonc/mdw235. Epub 2016 Jul 5.

  PMID: 27380959 BACKGROUND

• Morano F, Corallo S, Lonardi S, Raimondi A, Cremolini C, Rimassa L, Murialdo R, Zaniboni A, Sartore-Bianchi A, Tomasello G, Racca P, Clavarezza M, Adamo V, Perrone F, Gloghini A, Tamborini E, Busico A, Martinetti A, Palermo F, Loupakis F, Milione M, Fuca G, Di Bartolomeo M, de Braud F, Pietrantonio F. Negative Hyperselection of Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer Who Received Panitumumab-Based Maintenance Therapy. J Clin Oncol. 2019 Nov 20;37(33):3099-3110. doi: 10.1200/JCO.19.01254. Epub 2019 Sep 20.

  PMID: 31539295 BACKGROUND

• Vanderlaan PA, Yamaguchi N, Folch E, Boucher DH, Kent MS, Gangadharan SP, Majid A, Goldstein MA, Huberman MS, Kocher ON, Costa DB. Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer. Lung Cancer. 2014 Apr;84(1):39-44. doi: 10.1016/j.lungcan.2014.01.013. Epub 2014 Jan 28.

  PMID: 24513263 BACKGROUND

• Alix-Panabieres C, Pantel K. Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy. Cancer Discov. 2016 May;6(5):479-91. doi: 10.1158/2159-8290.CD-15-1483. Epub 2016 Mar 11.

  PMID: 26969689 BACKGROUND

• Merker JD, Oxnard GR, Compton C, Diehn M, Hurley P, Lazar AJ, Lindeman N, Lockwood CM, Rai AJ, Schilsky RL, Tsimberidou AM, Vasalos P, Billman BL, Oliver TK, Bruinooge SS, Hayes DF, Turner NC. Circulating Tumor DNA Analysis in Patients With Cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review. J Clin Oncol. 2018 Jun 1;36(16):1631-1641. doi: 10.1200/JCO.2017.76.8671. Epub 2018 Mar 5.

  PMID: 29504847 BACKGROUND

• Krebs MG, Metcalf RL, Carter L, Brady G, Blackhall FH, Dive C. Molecular analysis of circulating tumour cells-biology and biomarkers. Nat Rev Clin Oncol. 2014 Mar;11(3):129-44. doi: 10.1038/nrclinonc.2013.253. Epub 2014 Jan 21.

  PMID: 24445517 BACKGROUND

• Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42. doi: 10.1056/NEJMoa032691.

  PMID: 15175435 BACKGROUND

• Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pinter T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. doi: 10.1056/NEJMoa0805019.

  PMID: 19339720 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood sample collected from patient for this study, tumour or normal tissue removed or biopsied as part of patient's routine care and body fluids (e.g. fluid lining the lungs or effusion or fluid lining the abdomen or ascites) removed as part of patient's clinical care.

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Cheng Ean Chee

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cheng Ean Chee

CONTACT

+65 6779 5555; cheng_ean_chee@nuhs.edu.sg

Cheng Ean Chee

CONTACT

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2021
• First Posted: September 21, 2021
• Study Start: March 26, 2021
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: October 5, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)