Postoperative Chemotherapy With/Without Radiotherapy and Immunotherapy for Colorectal Liver Metastases With High Risk of Locally Recurrence

Phase 2

Recruiting

• Conditions: Liver Metastases; Radiotherapy; Immunotherapy; Colorectal Cancer
• Interventions: Radiation: SBRT; Drug: Chemotherapy; Drug: PD-1 antibody

• Registration Number: NCT06120127
• Lead Sponsor: Fudan University

Brief Summary

This study is a randomized controlled phase II trial to evaluate the efficacy of the combination of stereotactic body radiation therapy (SBRT) and immunotherapy with postoperative chemotherapy in colorectal cancer liver metastasis (CRLM) patients with high risk of locally recurrence. Researchers will compare the combination therapy with the postoperative chemotherapy alone to see if postoperative chemotherapy plus SBRT and immunotherapy can further reduce the risk of recurrence and metastasis after surgery.

Detailed Description

40-50% of colorectal cancer patients have metastases at the time of diagnosis, of which liver metastases are the most common. Surgical resection is the most likely cure for CRLM patients, however, more than 50% of patients will experience recurrence within 2 years after resection of liver metastases. SBRT can be an effective and safe treatment modality, which can not only provide better local control of metastatic lesions, but also has a sensitizing immunotherapeutic effect. SBRT can effectively synergize with anti-PD-1/PD-L1 antibodies to activate the immune microenvironment of CRLM patients and improve survival. However, in CRLM patients after surgery, whether combining SBRT, immunotherapy and adjuvant chemotherapy results in better survival than chemotherapy alone, the evidence is insufficient.

Study Timeline

• Study Start: 2023-09-25
• Status Verified: 2023-11
• Study First Submitted: 2023-11-02
• Study First Submitted QC: 2023-11-02
• Last Update Submitted: 2023-11-02
• Study First Posted: 2023-11-07
• Last Update Posted: 2023-11-07
• Primary Completion: 2025-09-25
• Study Completion: 2025-09-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. age ≥ 18 years old, female and male
2. pathological and imaging confirmed colorectal colorectal liver metastases (synchronous or heterochronous)
3. Metastatic liver lesions <= 5
4. Primary colorectal cancer under control
5. Absence of evidence of extra-hepatic diseases
6. Metastatic liver lesions received resection with insufficient margin (<0.5cm) or R1/R2 resection
7. Karnofsky >= 70
8. Adequate organ function without contraindications to surgery, radiotherapy and immunotherapy
9. Without previous antitumoral immunotherapy
10. With good compliance
11. Signed the inform consent

Exclusion Criteria

1. Pregnancy or breast-feeding women
2. History of other malignancies within 5 years (except cured skin cancer and cervical cancer in situ)
3. History of uncontrolled epilepsy, central nervous system disease, or psychiatric disorders
4. Clinically serious heart disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmia requiring pharmacologic intervention, or history of myocardial infarction within the last 12 months
5. Immunodeficiency disease, autoimmune diseases or long-term using of immunosuppressive agents
6. Severe uncontrolled recurrent infections
7. Baseline blood and biochemical indicator do not meet the following criteria: neutrophils >=1.5×10^9/L, Hb >=90g/L, PLT >=100×10^9/L, ALT/AST<=2.5 ULN, Cr <= 1ULN
8. Allergic to any component of the therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
chemotherapy with radiotherapy and immunotherapy	PD-1 antibody	radiotherapy: SBRT of liver lesions; postoperative chemotherapy and immunotherapy: chemotherapy by investigators' choice with sintilimab for 18 weeks
chemotherapy with radiotherapy and immunotherapy	SBRT	radiotherapy: SBRT of liver lesions; postoperative chemotherapy and immunotherapy: chemotherapy by investigators' choice with sintilimab for 18 weeks
chemotherapy with radiotherapy and immunotherapy	Chemotherapy	radiotherapy: SBRT of liver lesions; postoperative chemotherapy and immunotherapy: chemotherapy by investigators' choice with sintilimab for 18 weeks
chemotherapy	Chemotherapy	postoperative chemotherapy: chemotherapy by investigators' choice for 18 weeks

Primary Outcome Measures

Name	Time	Method
Progression free survival	From the date of randomization until the date of first documented progression or date of death from any cause, whichever come first, assessed up to 12 months	Evaluate the effect of the combination of adjuvant chemotherapy, SBRT and immunotherapy versus observation on progression free survival

Secondary Outcome Measures

Name	Time	Method
Local control rate	From the date of randomization until the date of first documented locally tumor recurrence, assessed up to 12 months	To evaluate local control rate after the combination of adjuvant chemotherapy, SBRT and immunotherapy in comparison to observation alone
Overall survival	From date of randomization until the date of death from any cause, assessed up to 36 months	To evaluate overall survival after the combination of adjuvant chemotherapy, SBRT and immunotherapy in comparison to observation alone
Grade 3-4 adverse effect rate	From date of randomization until the date of death from any cause, assessed up to 3 years	Rate of chemotherapy, SBRT and immunotherapy related adverse events

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China