Safety and Efficacy
Conditions
Keywords
MR-Linac, unresectable locally advanced colorectal cancer, neoadjuvant radiotherapy
Brief summary
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
RADIATIONMR-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.
Sponsors
Sichuan Cancer Hospital and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Patients over 18 years old 2. Patients can remain in a stationary position on the treatment bed for 1-1.5 hours 3. ECOG score 0-1 4. Pathological diagnosis of colon adenocarcinoma, clinical stage cT4N0-2M0 5. 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. 6. Able to adhere to the study protocol during the research period 7. Signed written informed consent
Exclusion criteria
1. Patients with dMMR or MSI-H 2. Presence of other types of tumors in addition to colon adenocarcinoma 3. Claustrophobia or inability to undergo MRI or treatment due to the presence of metal implants or other reasons 4. Distant metastasis (M1) 5. Pregnant or lactating women 6. Previous anti-tumor treatment 7. Concurrent use of prohibited drugs for treatment 8. Known history of positive human immunodeficiency virus testing or known acquired immunodeficiency syndrome. 9. 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 10. 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 11. Organ transplant surgery requiring immunosuppressive therapy 12. Severe, uncontrolled recurrent infections or other severe, uncontrolled comorbidities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MRI-linac Treatment Completion Rate | 2 years | Is adaptive radiotherapy guided by MRI feasible for patients with locally advanced unresectable colon cancer. The feasibility of each patient will be recorded as a binary variable (1=feasible; 0=not feasible). Completion Rate = Number of Completions / Total ITT Enrollment |
| Clinical complete response (cCR) | 2 years | Clinical complete response refers to the absence of detectable tumor clinically after treatment. Number of cCR cases/Number of cases completed for follow-up evaluation |
| Pathological complete response (pCR) | 2 years | Pathological complete response is defined as the absence of any signs of cancer in tissue samples after treatment. Number of pCR cases / Number of completed surgeries |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local control rate | 2 years | Proportion of cases in remission and stable disease after treatment, i.e., proportion of patients who did not experience disease progression. |
| Disease-free survival | 2 years | The time from the start of treatment to the first tumor recurrence/metastasis, or death of the subject due to any cause. |
| Overall survival | 2 years | Time from the start of the patient's treatment to the patient's death from any cause |
| Toxicity reaction (CTC 4.0 standard） | long range | CTC 4.0, also known as Common Terminology Criteria for Adverse Events version 4.0, is an extensively used classification system for assessing drug toxicity. This system categorizes drug toxicity into five levels: Grade 0, Grade 1, Grade 2, Grade 3, and Grade 4. |
| R0 resection rate | 2 years | During surgery, the R0 resection rate refers to the complete removal of the entire tumor with no residual abnormalities present in the surrounding normal tissue. R0 rate = Number of R0 cases / Total number of surgical procedures performed |
| Surgical complications | 2 years | Surgical complications refers to adverse events or problems that arise during or after a surgical procedure. These complications can range from minor issues to serious complications that may have significant consequences for the patient. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Online adaptation time, compliance rate, technical success rate | 8 months. | This pilot analysis was pre-specified in the registered protocol as an initial feasibility/run-in phase. Number of successful cases with the initial feasibility/run-in phase. |
Countries
China
Contacts
Primary ContactQian - Peng, chief physician
Outcome results
None listed