LDRT Combined With Immunochemotherapy for Colorectal Cancer With Liver Metastasis

Official title

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

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• Incidence of treatment-emergent adverse events [Time frame: 3 years]

Secondary outcome measures (3)

• Objective Response Rate (ORR) [Time frame: 2 years]
• Progression-free survival (PFS) [Time frame: 2 years]
• Overall survival (OS) [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Age between18 and 75 years old.
• Histopathological confirmed MSS/pMMR adenocarcinoma of the colon or rectum.
• The clinical baseline stage of rectal cancer assessed by MRI/CT/Transrectal ultrasound was T3-4Nx or TXN1-2.
• Simultaneous liver metastasis confirmed by imaging examination.
• No previous antitumor treatment.
• An Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• 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).
• Sign the informed consent and have good compliance.

Exclusion criteria

• Distant metastasis from other than the liver.
• 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).
• 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.
• 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.
• History of immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation and allogeneic bone marrow transplantation.
• 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%).
• 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).
• Pregnant or lactating women.
• 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.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Army Medical Center — Chongqing
• Daping Hospital, Army Medical University — Chongqing

Identifiers

NCT: NCT06848465 · DP2024348

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗