SBRT + PD-1 Monoclonal Antibody in Unresectable Colorectal Liver Metastases

NCT06794086 | Recruiting Phase 3

• 1 other identifier: E2024366
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

To explore the efficacy and safety of stereotactic body radiation therapy (SBRT) combined with PD-1 monoclonal antibody in the treatment of unresectable colorectal cancer liver metastasis through a prospective study, providing high-level evidence-based medical evidence for the use of SBRT combined with PD-1 inhibitors in the treatment of unresectable colorectal cancer liver metastasis.

Conditions

Colorectal Cancer; Liver Metastases

Keywords

Stereotactic body radiation therapy; PD-1 Monoclonal Antibody

Outcome Measures

Primary Outcomes (1)

• ORR

  Objective Response Rate

  1 year

Secondary Outcomes (8)

• DCR

  1 year

• pCR

  1 year

• 1 year PFS

  1 year

• 1 year OS

  1 year

• 2 years PFS

  2 years

Study Arms (1)

SBRT plus PD-1 Monoclonal Antibody

EXPERIMENTAL

Enrolled patients will receive stereotactic body radiation therapy with a dose of 8-12 Gy in 5 fractions. Chemotherapy based on 5-FU combined with PD-1 monoclonal antibody immunotherapy will be administered before and after radiotherapy.

Radiation: Stereotactic body radiation therapy; Drug: PD-1 Monoclonal Antibody; Drug: Chemotherapy

Interventions

Stereotactic body radiation therapy RADIATION

Stereotactic body radiation therapy (SBRT) is a highly precise form of external beam radiation therapy used to treat tumors in various parts of the body. Enrolled patients will initiate SBRT treatment within 2 weeks after the first course of chemotherapy. Intensity-modulated radiation therapy (IMRT) will be used, with the gross tumor volume (GTV) receiving a dose of 8-12 Gy in 5 fractions, resulting in a total dose of 40-60 Gy. The biologically effective dose (BED) is equivalent to 72-132 Gy. The treatment will be administered from Monday to Friday.

SBRT plus PD-1 Monoclonal Antibody

PD-1 Monoclonal Antibody DRUG

PD-1 monoclonal antibody is a type of immunotherapy drug designed to treat various cancers by targeting the programmed death receptor-1 (PD-1) pathway.The PD-1 monoclonal antibody used in this study is sintilimab at a dose of 200 mg, administered via intravenous infusion on Day 1. Participants will be considered eligible only if they have completed four or more cycles of PD-1 monoclonal antibody treatment both before and after SBRT.

Also known as: sintilimab

SBRT plus PD-1 Monoclonal Antibody

Chemotherapy DRUG

Chemotherapy regimens based on fluorouracil (5-FU), such as CAPOX with a 3-week cycle or mFOLFOX6/FOLFIRI/FOLFOXIRI with a 2-week cycle, may be combined with targeted therapy. During chemotherapy or chemoradiotherapy, optimal supportive care will be provided.

Also known as: fluorouracil

SBRT plus PD-1 Monoclonal Antibody

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent, voluntarily signed and dated by the subject, must be obtained in accordance with regulatory and institutional guidelines before any procedures related to the study protocol that are not part of routine care are performed.
• Patients with pMMR/MSS colorectal adenocarcinoma;
• Age 18-75 years;
• Patients with histologically or cytologically confirmed colorectal cancer liver metastasis, with or without extrahepatic oligometastatic lesions, who are deemed by the hepatobiliary surgeon within the multidisciplinary team (MDT) to be ineligible for upfront R0 resection of liver metastases (unresectability is defined as one or more of the following conditions: ① Involvement of both left and right branches of the portal vein at the first hepatic hilum; ② Involvement of ≥2 hepatic veins at the second hepatic hilum; ③ No indication for upfront R0 resection/ablation after MDT discussion);
• Liver metastases are measurable by imaging (based on RECIST 1.1 criteria), with a maximum diameter of ≤6 cm;
• Patients who have not previously received radiotherapy for liver metastases, or whose liver tissue near the planned irradiation site has not been previously irradiated, and who have at least 700 cc of liver volume outside the treatment area;
• Previous hepatectomy, systemic chemotherapy, or local ablation therapy, or hepatic arterial infusion pump chemotherapy is allowed, with a washout period of 2 weeks;
• Child-Pugh score Class A ;
• ECOG performance status 0-1;
• Peripheral blood counts and liver and renal function within allowable ranges (tested within 15 days before the start of treatment);
• No history of other malignancies, not pregnant or breastfeeding, and effective contraception should be used during the study period and for 6 months after the last dose;
• Life expectancy of ≥6 months.

You may not qualify if:

• Active hepatitis, cirrhosis, or Child-Pugh score Class B or C;
• Extrahepatic metastases: bone or brain metastases, or ≥3 unresectable lung metastases (according to the 8th edition of the UICC);
• Unmeasurable liver metastases;
• History of severe drug allergies (including allergies to platinum agents, 5-FU, LV, and 5-HT3 receptor antagonists);
• Patients who have participated in or are currently participating in other clinical trials within the past 4 weeks;
• History of prior treatment with anti-PD-1, PD-L1, PD-L2, CTLA-4, or any other specific T-cell costimulatory or checkpoint pathway-targeted therapies;
• Severe electrolyte abnormalities;
• History of arterial thrombosis or deep vein thrombosis within 6 months; history of bleeding or evidence of bleeding tendency within 2 months;
• Pregnant or breastfeeding women, or women of childbearing potential with a positive pregnancy test before the first dose; or female participants unwilling to strictly practice contraception during the study, as well as their partners;
• Patients with active autoimmune deficiency diseases requiring systemic treatment within the past 2 years (i.e., use of immunomodulators, corticosteroids, or immunosuppressive drugs);
• Presence of other active malignancies (except for malignancies that have been treated with curative intent and have been disease-free for over 3 years, or in situ cancers that can be cured with adequate treatment);
• Presence of severe ECG abnormalities or active coronary artery disease within 12 months before study entry, severe/unstable angina, newly diagnosed angina or myocardial infarction, or New York Heart Association (NYHA) Class II or higher congestive heart failure;
• Patients with active infections (fever above 38°C due to infection);
• Patients with poorly controlled hypercalcemia, hypertension, or diabetes;
• Patients with severe pulmonary diseases (interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc.);

Sponsors & Collaborators

• Jun Huang: lead

Study Sites (1)

Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510065, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Radiosurgery; spartalizumab; sintilimab; Drug Therapy; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jun Huang, PhD.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Huang, PhD.

CONTACT

13926451242; huangj97@mail.sysu.edu.cn

Fang He, MD.

CONTACT

18826059789; hefang23@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: SBRT plus PD-1 Monoclonal Antibody

Study Record Dates

• First Submitted: January 20, 2025
• First Posted: January 27, 2025
• Study Start: April 10, 2025
• Primary Completion: January 20, 2026
• Study Completion (Estimated): January 20, 2027
• Last Updated: May 13, 2025

Record last verified: 2025-05

Locations

CN (1)