LDRT Combined With Immunochemotherapy for Colorectal Cancer With Liver Metastasis

A Phase Ib Trial on the Safety and Feasibility of Low Dose Radiotherapy (LDRT) Combined With Immunochemotherapy for Colorectal Cancer With Liver-limited Metastasis

In recent years, growing evidences have demonstrated promising synergistic antitumor effects of radiotherapy combined with immunotherapy. More over, LDRT may enhance the antitumor effect of immunotherapy by altering the tumor immune microenvironment (TIME) and adjusting the immune response. In this study, we will explore the safety and feasibility of LDRT and immunochemotherapy in liver metastatic colorectal cancer. 9-18 participants will be enrolled in this study. All will take part at Daping Hospital, Army Medical University.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Liver Metastasis; LDRT
• Intervention / Treatment: Radiation: Low Dose Radiotherapy; Radiation: Short course Radiotherapy; Drug: XELOX; Drug: Tislelizumab

Detailed Description

This is a prospective, single-arm, phase Ib trial. At least 9 eligible patients will be will be enrolled In this study. Patients will receive LDRT of 10 Gy in 5 fractions, 15 Gy in 5 fractions, 20 Gy in 10 fractions respectively in our three groups on liver metastsis from Day1 (patients with rectal cancer will receive SCRT concurrently), followed by Xelox and Tislelizumab starting from 1 week after the completion of radiation. The primary endpoints are safety and tolerability.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Chuan Chen, MD PhD; Phone Number: 13883089634; Email: sinkriver@126.com

Study Locations

• China
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400042
      • Recruiting
      • Army Medical Center
      • Contact: Chuan Chen, Doctor; Phone Number: 023-13883089634; Email: sinkriver@126.com
    • Chongqing, Chongqing Municipality, China, 400042
      • Active, not recruiting
      • Daping Hospital, Army Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between18 and 75 years old.
2. Histopathological confirmed MSS/pMMR adenocarcinoma of the colon or rectum.
3. The clinical baseline stage of rectal cancer assessed by MRI/CT/Transrectal ultrasound was T3-4Nx or TXN1-2.
4. Simultaneous liver metastasis confirmed by imaging examination.
5. No previous antitumor treatment.
6. An Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
7. Adequate cardiac function (Left Ventricular Ejection Fractions > 50%), hepatic function (total serum bilirubin ≤ 1.5 × upper limit of normal, alanine aminotransferase or aspartate aminotransferase ≤ 2.5 × upper limit of normal), renal function (serum creatinine ≤ 1.5 × ULN or glomerular filtration rate > 60 ml/min, based on Cockcroft-Gault), and hematopoietic function (white blood cells ≥ 4.0 × 109 cells per L, neutrophils ≥ 1.5 × 109 cells per L, hemoglobin ≥ 90 g/L, platelets ≥ 100 × 109 cells per L).
8. Sign the informed consent and have good compliance.

Exclusion Criteria:

1. Distant metastasis from other than the liver.
2. BMI < 18.5 kg/m² or weight loss ≥ 10% within the past 6 months (with consideration of the impact of large amounts of pleural and ascitic fluid on body weight).
3. Received any of the following treatments: any investigational drug; enrolled in another clinical trial concurrently, unless it is an observational (non-interventional) clinical study; received anti-tumor vaccines or live vaccines.
4. Active autoimmune diseases, or a history of autoimmune diseases. A history of liver disease including, but not limited to HBV infection or HBV DNA positive(≥1×10^4/ml), HCV infection or HCV DNA positive(≥1×10^3/ml) and liver cirrhosis.
5. History of immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation and allogeneic bone marrow transplantation.
6. A history of heart disease within 6 months (including congestive heart failure, acute myocardial infarction, severe/unstable angina, coronary artery bypass grafting, cardiac insufficiency ≥ NYHA grade 2 and LVEF<50%).
7. The presence of a clinically detectable second primary malignancy, or history of other malignancies within 5 years excluding adequately treated non-melanoma skin cancer, carcinoma in situ of cervix and superficial bladder tumour (non-invasive tumour, or carcinoma in situ, or T1).
8. Pregnant or lactating women.
9. The investigator considers that the subject is not suitable to participate in this clinical study due to any clinical or laboratory abnormalities or compliance problems.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: LDRT/LDRT+SCRT followed by Tislelizumab+XELOX; For patients with colon Cancer: LDRT starts from day 1. For patients with rectal Cancer: LDRT and SCRT start concurrently from day 1. Tislelizumab+XELOX start from 1week after the completion of radiotherapy (2-4 cycles).

Radiation: Low Dose Radiotherapy; 10 Gy in 5 fractions, 15 Gy in 3 fractions, 20 Gy in 10 fractions respectively in three Cohorts from Day1; Radiation: Short course Radiotherapy; 25 Gy in 5 fractions from Day1; Drug: XELOX; Oxaliplatin: 130mg/m2 IV Q3W on day 1 of each cycle. Capecitabine: 1000mg/m2 Q3W Dose of 1000mg/m2 on day 1-14 of each cycle.; Drug: Tislelizumab; 200mg IV Q3W on day 1 of each cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events	Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measurement of Safety and tolerability of LDRT in Combination With Tirellizumab and XELOX	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Investigator assessed ORR using RECIST v1.1 including the all tumor	2 years
Progression-free survival (PFS)	Defined as the time from initiation of treatment to tumor progression or death from any cause.	2 years
Overall survival (OS)	Defined as the time from initiation of treatment to death from any cause.	3 years

Collaborators and Investigators

• Sponsor: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
• Investigators: Study Director: Chuan Chen, MD PhD, Daping Hospital, Army Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2025
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: January 22, 2025
• First Submitted That Met QC Criteria: February 23, 2025
• First Posted (Actual): February 27, 2025

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Therapeutics; Radiotherapy; tislelizumab; XELOX
• Other Study ID Numbers: DP2024348

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No