Clinical trial NCT06654622: Exosome-based Detection of Molecular Residual Disease in Stage II-III Colorectal Cancer
Official title: An Exosome-Based Liquid Biopsy Assay to Detect Molecular Residual Disease for the Identification of High-Risk Patients With Stage II-III Colorectal Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Colo-rectal Cancer
Colorectal Cancer Recurrent
Keywords: Colorectal cancer
Molecular residual disease
Adjuvant chemotherapy
Stage II-III CRC
exosomal miRNA
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
First posted: 2024-10-23
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: The study will enroll patients with stage II-III colorectal cancer who have undergone curative surgery and require assessment for molecular residual disease to determine whether adjuvant chemotherapy is necessary.

Brief summary: This study aims to establish an exosome-based liquid biopsy signature to detect molecular residual disease (MRD) in stage II-III colorectal cancer (CRC) patients. Identifying patients with MRD after surgery is crucial for selecting appropriate candidates for adjuvant chemotherapy (ACT), allowing for more personalized treatment approaches and potentially improving patient outcomes.

Detailed description: The current standard for treating stage II-III colorectal cancer involves surgical resection, often followed by adjuvant chemotherapy (ACT) for high-risk patients. However, identifying patients who would benefit most from ACT remains challenging. Molecular residual disease (MRD) in these patients is a critical factor in determining the likelihood of recurrence. This study aims to develop an exosome-based liquid biopsy assay using circulating exosomal microRNAs (exo-miRNAs) to predict the presence of MRD in postoperative patients. By analyzing exo-miRNAs from blood samples collected after surgery, the goal is to identify high-risk patients who may benefit from ACT while sparing low-risk patients from unnecessary treatment. A risk-stratification model, termed the exosome-based molecular residual disease prediction for adjuvant chemotherapy induction (EMRATI) score, will be developed to improve ACT decision-making and enhance clinical outcomes for stage II-III CRC patients.

Eligibility criteria: Inclusion Criteria:

1. Patients with pathologically confirmed stage II or III colorectal cancer.
2. Patients who have undergone curative-intent surgery.
3. Patients with no evidence of distant metastasis (stage IV).
4. Patients aged 18 years or older.
5. Patients who provided written informed consent.

Exclusion Criteria:

1. Patients with stage IV cancer or those receiving neoadjuvant therapy.
2. Patients with non-curative resection or requiring urgent surgery.
3. Patients with a follow-up period of fewer than 3 years.
4. Patients with severe comorbidities or who are unable to participate in follow-up assessments.

Primary outcomes:
measure: Tumor Evaluation (Recurrence)
timeFrame: Follow-up at regular intervals during the first 3 years post-surgery.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Patients will be monitored for overall survival for up to 5 years post-surgery.
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Ajay Goel, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhou H, Zhu L, Song J, Wang G, Li P, Li W, Luo P, Sun X, Wu J, Liu Y, Zhu S, Zhang Y. Liquid biopsy at the frontier of detection, prognosis and progression monitoring in colorectal cancer. Mol Cancer. 2022 Mar 25;21(1):86. doi: 10.1186/s12943-022-01556-2.
citation: Ruiz-Banobre J, Roy R, Alustiza Fernandez M, Murcia O, Jover R, Pera M, Balaguer F, Lopez-Lopez R, Goel A. Clinical significance of a microRNA signature for the identification and predicting prognosis in colorectal cancers with mucinous differentiation. Carcinogenesis. 2020 Nov 13;41(11):1498-1506. doi: 10.1093/carcin/bgaa097.
citation: Matsuyama T, Toiyama Y, Ishikawa T, Okugawa Y, Yasuno M, Maurel J, Kinugasa Y, Uetake H, Goel A. A metastasis-associated microRNA-based liquid biopsy signature for risk-stratification in colorectal cancer: a multicenter cohort study. Clin Transl Med. 2022 Dec;12(12):e998. doi: 10.1002/ctm2.998. No abstract available.
citation: Miyazaki K, Wada Y, Okuno K, Murano T, Morine Y, Ikemoto T, Saito Y, Ikematsu H, Kinugasa Y, Shimada M, Goel A. An exosome-based liquid biopsy signature for pre-operative identification of lymph node metastasis in patients with pathological high-risk T1 colorectal cancer. Mol Cancer. 2023 Jan 6;22(1):2. doi: 10.1186/s12943-022-01685-8.
citation: Mo S, Ye L, Wang D, Han L, Zhou S, Wang H, Dai W, Wang Y, Luo W, Wang R, Xu Y, Cai S, Liu R, Wang Z, Cai G. Early Detection of Molecular Residual Disease and Risk Stratification for Stage I to III Colorectal Cancer via Circulating Tumor DNA Methylation. JAMA Oncol. 2023 Jun 1;9(6):770-778. doi: 10.1001/jamaoncol.2023.0425.
citation: Yoshino T, Argiles G, Oki E, Martinelli E, Taniguchi H, Arnold D, Mishima S, Li Y, Smruti BK, Ahn JB, Faud I, Chee CE, Yeh KH, Lin PC, Chua C, Hasbullah HH, Lee MA, Sharma A, Sun Y, Curigliano G, Bando H, Lordick F, Yamanaka T, Tabernero J, Baba E, Cervantes A, Ohtsu A, Peters S, Ishioka C, Pentheroudakis G. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer. Ann Oncol. 2021 Dec;32(12):1496-1510. doi: 10.1016/j.annonc.2021.08.1752. Epub 2021 Aug 16.
citation: Montcusi B, Madrid-Gambin F, Marin S, Mayol X, Pascual M, Cascante M, Pozo OJ, Pera M. Circulating Metabolic Markers Identify Patients at Risk for Tumor Recurrence: A Prospective Cohort Study in Colorectal Cancer Surgery. Ann Surg. 2024 Nov 1;280(5):842-849. doi: 10.1097/SLA.0000000000006463. Epub 2024 Aug 1.
citation: Kotani D, Oki E, Nakamura Y, Yukami H, Mishima S, Bando H, Shirasu H, Yamazaki K, Watanabe J, Kotaka M, Hirata K, Akazawa N, Kataoka K, Sharma S, Aushev VN, Aleshin A, Misumi T, Taniguchi H, Takemasa I, Kato T, Mori M, Yoshino T. Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer. Nat Med. 2023 Jan;29(1):127-134. doi: 10.1038/s41591-022-02115-4. Epub 2023 Jan 16.
citation: Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, Wong R, Shapiro J, Lee M, Harris S, Khattak A, Burge M, Harris M, Lynam J, Nott L, Day F, Hayes T, McLachlan SA, Lee B, Ptak J, Silliman N, Dobbyn L, Popoli M, Hruban R, Lennon AM, Papadopoulos N, Kinzler KW, Vogelstein B, Tomasetti C, Gibbs P; DYNAMIC Investigators. Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. N Engl J Med. 2022 Jun 16;386(24):2261-2272. doi: 10.1056/NEJMoa2200075. Epub 2022 Jun 4.
citation: Kandimalla R, Gao F, Matsuyama T, Ishikawa T, Uetake H, Takahashi N, Yamada Y, Becerra C, Kopetz S, Wang X, Goel A. Genome-wide Discovery and Identification of a Novel miRNA Signature for Recurrence Prediction in Stage II and III Colorectal Cancer. Clin Cancer Res. 2018 Aug 15;24(16):3867-3877. doi: 10.1158/1078-0432.CCR-17-3236. Epub 2018 Mar 7.