Study on the Safety and Efficacy of MR-Linac Technique in Patients With Unresectable Locally Advanced Colon Cancer

Overview

In this phase I single-arm clinical study, 20 patients with T4 unresectable locally advanced colon cancer are proposed to be enrolled, who will be treated with MR-Linac with short course radiotherapy (25Gy/5F), followed by 4 cycles of mFOLFOX6 or 3 cycles of XELOX chemotherapy, then radical surgical resection, and then postoperatively with 8 cycles of mFOLFOX6 or 5 cycles of XELOX. The study will assess patients' surgical R0 resection rate, pCR or cCR rate, PFS, OS, and related adverse effects of treatment, aiming to explore the feasibility, safety, and efficacy of MR-Linac in the treatment of unresectable locally advanced colon cancer.

Detailed description

Pre-specified run-in/feasibility phase. As outlined in the registered protocol, this record includes an initial feasibility (run-in) phase conducted under the same eligibility criteria and intervention as the definitive efficacy/safety phase. The run-in is designed solely to evaluate operational and workflow feasibility. The run-in is not powered for efficacy and will not test efficacy or survival hypotheses.

Pre-specified feasibility thresholds for proceeding include, for example: protocol adherence ≥85-90%, adaptive-plan success ≥80-90%, and accrual feasibility ≥80% of the target. The run-in sample size is capped (≈24 patients), and its endpoints/time frames are listed under Outcome Measures. Meeting these thresholds triggers continuation to the definitive phase without changing the intervention or eligibility.

Interventions

• Radiation MR-linac
  Patients enrolled will be treated with MR-Linac with short course radiotherapy (25Gy/5F), followed by 4 cycles of mFOLFOX6 or 3 cycles of XELOX chemotherapy, then radical surgical resection, and then postoperatively with 8 cycles of mFOLFOX6 or 5 cycles of XELOX chemotherapy.

Primary outcome measures

• MRI-linac Treatment Completion Rate [Time frame: 2 years]
• Clinical complete response (cCR) [Time frame: 2 years]
• Pathological complete response (pCR) [Time frame: 2 years]

Secondary outcome measures (6)

• Toxicity reaction (CTC 4.0 standard） [Time frame: long range]
• R0 resection rate [Time frame: 2 years]
• Surgical complications [Time frame: 2 years]
• Local control rate [Time frame: 2 years]
• Disease-free survival [Time frame: 2 years]
• Overall survival [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Patients over 18 years old
• Patients can remain in a stationary position on the treatment bed for 1-1.5 hours
• ECOG score 0-1
• Pathological diagnosis of colon adenocarcinoma, clinical stage cT4N0-2M0
• Organ function is normal, and the following conditions are required: white blood cell count ≥3.5×10\^9/L; platelet count ≥100×10\^9/L; hemoglobin ≥90g/L. Total bilirubin level ≤1.5× upper limit of normal (ULN); AST and ALT levels ≤2.5 × ULN; endogenous creatinine clearance rate: 56-122ml/min; serum creatinine <1.0× ULN; serum albumin ≥30g/L.
• Able to adhere to the study protocol during the research period
• Signed written informed consent

Exclusion criteria

• Patients with dMMR or MSI-H
• Presence of other types of tumors in addition to colon adenocarcinoma
• Claustrophobia or inability to undergo MRI or treatment due to the presence of metal implants or other reasons
• Distant metastasis (M1)
• Pregnant or lactating women
• Previous anti-tumor treatment
• Concurrent use of prohibited drugs for treatment
• Known history of positive human immunodeficiency virus testing or known acquired immunodeficiency syndrome.
• Clinically significant (i.e., active) cardiovascular disease: cerebrovascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina pectoris, congestive heart failure (≥New York Heart Association class II) or severe arrhythmia requiring medication treatment
• Individuals with uncontrolled epilepsy, central nervous system disorders or a history of mental illness, whose clinical severity may hinder signing informed consent or affect patient compliance with oral medication according to the investigator's judgement
• Organ transplant surgery requiring immunosuppressive therapy
• Severe, uncontrolled recurrent infections or other severe, uncontrolled comorbidities

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electroni — Chengdu

Publications

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID 33538338
• Cao W, Chen HD, Yu YW, Li N, Chen WQ. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl). 2021 Mar 17;134(7):783-791. doi: 10.1097/CM9.0000000000001474. PMID 33734139
• Yoshihara M, Hiyama T, Tanaka S. [Epidemiology of colorectal cancer]. Nihon Naika Gakkai Zasshi. 2007 Feb 10;96(2):200-6. doi: 10.2169/naika.96.200. No abstract available. Japanese. PMID 17370582
• Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25. PMID 26808342
• Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, Nordlinger B, van de Velde CJ, Balmana J, Regula J, Nagtegaal ID, Beets-Tan RG, Arnold D, Ciardiello F, Hoff P, Kerr D, Kohne CH, Labianca R, Price T, Scheithauer W, Sobrero A, Tabernero J, Aderka D, Barroso S, Bodoky G, Douillard JY, El Ghazaly H, Gallardo J, Garin A, Glynne-Jones R, Jordan K, Meshcheryakov A, Papamichail PMID 23012255
• Wu C. Systemic Therapy for Colon Cancer. Surg Oncol Clin N Am. 2018 Apr;27(2):235-242. doi: 10.1016/j.soc.2017.11.001. Epub 2017 Dec 16. PMID 29496087
• Karoui M, Rullier A, Luciani A, Bonnetain F, Auriault ML, Sarran A, Monges G, Trillaud H, Le Malicot K, Leroy K, Sobhani I, Bardier A, Moreau M, Brindel I, Seitz JF, Taieb J. Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial--the PRODIGE 22--ECKINOXE trial. BMC Cancer. 2015 J PMID 26156156
• Chang H, Yu X, Xiao WW, Wang QX, Zhou WH, Zeng ZF, Ding PR, Li LR, Gao YH. Neoadjuvant chemoradiotherapy followed by surgery in patients with unresectable locally advanced colon cancer: a prospective observational study. Onco Targets Ther. 2018 Jan 17;11:409-418. doi: 10.2147/OTT.S150367. eCollection 2018. PMID 29398921

Identifiers

NCT: NCT06244537 · SCCHEC-02-2024-017

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗