Splicing-based Predictive Learning for Individual Chemotherapy Evaluation in Colorectal Cancer

NCT07226115 | Recruiting

• 1 other identifier: 23228/SPLICE
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Although adjuvant chemotherapy improves survival after curative resection, its efficacy varies widely among patients. The absence of reliable predictive biomarkers often leads to overtreatment or undertreatment. This study aims to develop a machine learning-based predictive model for adjuvant chemotherapy response using tumor-derived alternative splicing signatures. By integrating RNA-seq data, splicing isoform and clinical outcomes, this study seeks to identify molecular predictors of treatment response and recurrence risk after surgery.

Conditions

Colorectal Cancer; Colorectal Cancer Recurrent; Colorectal Cancer Stage II; Colorectal Cancer Stage III

Keywords

Chemotherapy; Adjuvant; Response; Splicing; Prediction

Outcome Measures

Primary Outcomes (1)

• Recurrence Free Survival

  Time from disease treatment to development of recurrent colorectal cancer

  from date of disease treatment to date of death or up to 60 months

Secondary Outcomes (1)

• Overall survival

  from date of disease treatment to date of death or up to 60 months

Study Arms (4)

Non-responders of colorectal cancer (Training Cohort)

Non-responders of colorectal cancer who developed recurrent CRC within 60 months from primary tumor treatment, in the first cohort

Other: SPLICE

Responders of colorectal cancer (Training Cohort)

Responders of colorectal cancer who did not develop recurrent CRC within 60 months from primary tumor treatment, in the first cohort

Other: SPLICE

Non-responders of colorectal cancer, with recurrent disease (Validation Cohort)

Non-responders of colorectal cancer who developed recurrent CRC within 60 months from primary tumor treatment, in the second, independent, validation cohort

Other: SPLICE

Responders of colorectal cancer (Validation Cohort)

Responders of colorectal cancer who did not develop recurrent CRC within 60 months from primary tumor treatment, in the second, independent, validation cohort

Other: SPLICE

Interventions

SPLICE OTHER

A panel of RNA splicing isoform, whose level is tested in tissue samples derived from the primary tumor.

Non-responders of colorectal cancer (Training Cohort); Non-responders of colorectal cancer, with recurrent disease (Validation Cohort); Responders of colorectal cancer (Training Cohort); Responders of colorectal cancer (Validation Cohort)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Two independent cohorts of colorectal cancer patients treated with adjuvant chemotherapy after curative-intent surgery.

You may qualify if:

• Histologically confirmed stage II-III colorectal cancer (TNM classification, 8th edition)
• Received standard adjuvant chemotherapy after curative resection
• Availability of tumor tissue (FFPE or frozen) before chemotherapy
• Sufficient clinical data for outcome analysis (recurrence, survival)
• Age 18-80 years Stage

You may not qualify if:

• Inflammatory bowel disease
• Inadequate RNA quality or lack of consent

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Related Publications (10)

• Dienstmann R, Salazar R, Tabernero J. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients. J Clin Oncol. 2015 Jun 1;33(16):1787-96. doi: 10.1200/JCO.2014.60.0213. Epub 2015 Apr 27.

  PMID: 25918287 BACKGROUND

• Di Narzo AF, Tejpar S, Rossi S, Yan P, Popovici V, Wirapati P, Budinska E, Xie T, Estrella H, Pavlicek A, Mao M, Martin E, Scott W, Bosman FT, Roth A, Delorenzi M. Test of four colon cancer risk-scores in formalin fixed paraffin embedded microarray gene expression data. J Natl Cancer Inst. 2014 Sep 22;106(10):dju247. doi: 10.1093/jnci/dju247. Print 2014 Oct.

  PMID: 25246611 BACKGROUND

• Auclin E, Zaanan A, Vernerey D, Douard R, Gallois C, Laurent-Puig P, Bonnetain F, Taieb J. Subgroups and prognostication in stage III colon cancer: future perspectives for adjuvant therapy. Ann Oncol. 2017 May 1;28(5):958-968. doi: 10.1093/annonc/mdx030.

  PMID: 28453690 BACKGROUND

• Andre T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009 Jul 1;27(19):3109-16. doi: 10.1200/JCO.2008.20.6771. Epub 2009 May 18.

  PMID: 19451431 BACKGROUND

• Andre T, Meyerhardt J, Iveson T, Sobrero A, Yoshino T, Souglakos I, Grothey A, Niedzwiecki D, Saunders M, Labianca R, Yamanaka T, Boukovinas I, Vernerey D, Meyers J, Harkin A, Torri V, Oki E, Georgoulias V, Taieb J, Shields A, Shi Q. Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials. Lancet Oncol. 2020 Dec;21(12):1620-1629. doi: 10.1016/S1470-2045(20)30527-1.

  PMID: 33271092 BACKGROUND

• Okuno K, Kandimalla R, Mendiola M, Balaguer F, Bujanda L, Fernandez-Martos C, Aparicio J, Feliu J, Tokunaga M, Kinugasa Y, Maurel J, Goel A. A microRNA signature for risk-stratification and response prediction to FOLFOX-based adjuvant therapy in stage II and III colorectal cancer. Mol Cancer. 2023 Jan 20;22(1):13. doi: 10.1186/s12943-022-01699-2. No abstract available.

  PMID: 36670412 BACKGROUND

• Zhang JX, Song W, Chen ZH, Wei JH, Liao YJ, Lei J, Hu M, Chen GZ, Liao B, Lu J, Zhao HW, Chen W, He YL, Wang HY, Xie D, Luo JH. Prognostic and predictive value of a microRNA signature in stage II colon cancer: a microRNA expression analysis. Lancet Oncol. 2013 Dec;14(13):1295-306. doi: 10.1016/S1470-2045(13)70491-1. Epub 2013 Nov 13.

  PMID: 24239208 BACKGROUND

• Gray RG, Quirke P, Handley K, Lopatin M, Magill L, Baehner FL, Beaumont C, Clark-Langone KM, Yoshizawa CN, Lee M, Watson D, Shak S, Kerr DJ. Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. J Clin Oncol. 2011 Dec 10;29(35):4611-9. doi: 10.1200/JCO.2010.32.8732. Epub 2011 Nov 7.

  PMID: 22067390 BACKGROUND

• Zhang M, Chen C, Lu Z, Cai Y, Li Y, Zhang F, Liu Y, Chen S, Zhang H, Yang S, Gen H, Jiang Y, Ning C, Huang J, Wang W, Fan L, Zhang Y, Jin M, Han J, Xiong Z, Cai M, Liu J, Huang C, Yang X, Xu B, Li H, Li B, Zhu X, Wei Y, Zhu Y, Tian J, Miao X. Genetic Control of Alternative Splicing and its Distinct Role in Colorectal Cancer Mechanisms. Gastroenterology. 2023 Nov;165(5):1151-1167. doi: 10.1053/j.gastro.2023.07.019. Epub 2023 Aug 3.

  PMID: 37541527 BACKGROUND

• Reichling C, Taieb J, Derangere V, Klopfenstein Q, Le Malicot K, Gornet JM, Becheur H, Fein F, Cojocarasu O, Kaminsky MC, Lagasse JP, Luet D, Nguyen S, Etienne PL, Gasmi M, Vanoli A, Perrier H, Puig PL, Emile JF, Lepage C, Ghiringhelli F. Artificial intelligence-guided tissue analysis combined with immune infiltrate assessment predicts stage III colon cancer outcomes in PETACC08 study. Gut. 2020 Apr;69(4):681-690. doi: 10.1136/gutjnl-2019-319292. Epub 2019 Nov 28.

  PMID: 31780575 RESULT

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

• Ajay Goel, PhD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ajay Goel, PhD

CONTACT

626-218-3452; AJGOEL@COH.ORG

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2025
• First Posted: November 10, 2025
• Study Start: June 21, 2024
• Primary Completion (Estimated): June 18, 2026
• Study Completion (Estimated): June 18, 2026
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)