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

Phase 3

Recruiting

• Conditions: Colorectal Cancer; Liver Metastases
• Interventions: Radiation: Stereotactic body radiation therapy; Drug: PD-1 Monoclonal Antibody; Drug: Chemotherapy

• Registration Number: NCT06794086
• Lead Sponsor: Jun Huang

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.

Detailed Description

For patients with unresectable colorectal cancer liver metastasis, this study aims to explore whether the combination of stereotactic body radiation therapy (SBRT) and PD-1 monoclonal antibody can improve the objective response rate (ORR), achieve better long-term survival benefits, and enhance quality of life. Additionally, the study will investigate the efficacy and safety of SBRT combined with PD-1 monoclonal antibody for treating liver metastases, with the goal of providing high-level evidence-based medical evidence for the use of local hypofractionated radiotherapy combined with PD-1 monoclonal antibody in the treatment of unresectable colorectal cancer liver metastasis.

This is a prospective, open-label, multicenter, single-arm, Phase II study. Patients with colorectal cancer will be eligible for enrollment if the hepatobiliary surgery team within the multidisciplinary team (MDT) deems the liver metastases unresectable, and the radiation oncology team within the MDT considers the liver metastases suitable for stereotactic body radiation therapy (SBRT).

Enrolled patients will receive hypofractionated radiotherapy with a dose of 8-12 Gy in 5 fractions. Chemotherapy based on 5-FU combined with immunotherapy will be administered before and after radiotherapy. Eight weeks (±2 weeks) after the completion of radiotherapy, radiological assessment or multi-site liver biopsy will be performed. The MDT will then decide on the subsequent management: maintenance chemotherapy or watch-and-wait (W\&W) for patients achieving complete clinical response (cCR) or pathological complete response (pCR), or maintenance chemotherapy or discontinuation for patients who do not achieve cCR/pCR.

Study Timeline

• Study First Submitted: 2025-01-20
• Study First Submitted QC: 2025-01-20
• Study First Posted: 2025-01-27
• Study Start: 2025-04-10
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-10
• Last Update Posted: 2025-05-13
• Primary Completion: 2026-01-20
• Study Completion: 2027-01-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. 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.
2. Patients with pMMR/MSS colorectal adenocarcinoma;
3. Age 18-75 years;
4. 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);
5. Liver metastases are measurable by imaging (based on RECIST 1.1 criteria), with a maximum diameter of ≤6 cm;
6. 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;
7. Previous hepatectomy, systemic chemotherapy, or local ablation therapy, or hepatic arterial infusion pump chemotherapy is allowed, with a washout period of 2 weeks;
8. Child-Pugh score Class A ;
9. ECOG performance status 0-1;
10. Peripheral blood counts and liver and renal function within allowable ranges (tested within 15 days before the start of treatment);
11. 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;
12. Life expectancy of ≥6 months.

Exclusion Criteria

1. Active hepatitis, cirrhosis, or Child-Pugh score Class B or C;
2. Extrahepatic metastases: bone or brain metastases, or ≥3 unresectable lung metastases (according to the 8th edition of the UICC);
3. Unmeasurable liver metastases;
4. History of severe drug allergies (including allergies to platinum agents, 5-FU, LV, and 5-HT3 receptor antagonists);
5. Patients who have participated in or are currently participating in other clinical trials within the past 4 weeks;
6. 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;
7. Severe electrolyte abnormalities;
8. Presence of gastrointestinal diseases, such as active gastric or duodenal ulcers, ulcerative colitis, or unresected tumors with active bleeding; or other conditions that may lead to gastrointestinal bleeding or perforation (Note: Gastrointestinal fistulas that have not healed after surgical treatment, such as rectovesical, rectourethral, or rectovaginal fistulas, are exclusionary unless a stoma has been created and there are no active symptoms);
9. History of arterial thrombosis or deep vein thrombosis within 6 months; history of bleeding or evidence of bleeding tendency within 2 months;
10. 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;
11. Patients with active autoimmune deficiency diseases requiring systemic treatment within the past 2 years (i.e., use of immunomodulators, corticosteroids, or immunosuppressive drugs);
12. 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);
13. 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;
14. Patients with active infections (fever above 38°C due to infection);
15. Patients with poorly controlled hypercalcemia, hypertension, or diabetes;
16. Patients with severe pulmonary diseases (interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc.);
17. Patients with psychiatric disorders affecting clinical management or a history of central nervous system diseases;
18. Patients with severe complications (intestinal obstruction, renal insufficiency, hepatic insufficiency, cerebrovascular disorders, etc.);
19. Presence of any CTCAE Grade 2 or higher toxicity from prior treatments that has not resolved (except for anemia, alopecia, and skin pigmentation);
20. Any unstable medical condition that may affect patient safety or compliance with the study;
21. Patients deemed by the investigator to be unsuitable for participation in this clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SBRT plus PD-1 Monoclonal Antibody	Stereotactic body radiation therapy	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.
SBRT plus PD-1 Monoclonal Antibody	Chemotherapy	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.
SBRT plus PD-1 Monoclonal Antibody	PD-1 Monoclonal Antibody	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.

Primary Outcome Measures

Name	Time	Method
ORR	1 year	Objective Response Rate

Secondary Outcome Measures

Name	Time	Method
DCR	1 year	Disease Control Rate
pCR	1 year	Pathological Complete Response
1 year PFS	1 year	Local Progression-Free Survival of 1 Year
1 year OS	1 year	Overall Survival of 1 Year
2 years PFS	2 years	Local Progression-Free Survival of 2 Years
2 years OS	2 years	Overall Survival of 2 Years
R0 resection rate	1 year	The Rate of Negative margins under microscopy
Acute toxicity reactions	1 year	Referring to the percentage of patients experiencing acute toxicities related to radiotherapy, chemotherapy, and immunotherapy

Trial Locations

Locations (1)

Sixth Affiliated Hospital, Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China