Clinical trial NCT06120127: Postoperative Chemotherapy With/Without Radiotherapy and Immunotherapy for Colorectal Liver Metastases With High Risk of Locally Recurrence
Official title: Postoperative Chemotherapy With/Without Radiotherapy and Immunotherapy for Colorectal Liver Metastases With High Risk of Locally Recurrence: A Randomized Controlled Phase II Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Radiotherapy
Immunotherapy
Liver Metastases
Colorectal Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2023-11-07
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: adjuvant radiotherapy: SBRT; immunotherapy: sintilimab chemotherapy: XELOX
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: 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
Secondary outcomes:
measure: Local control rate
timeFrame: From the date of randomization until the date of first documented locally tumor recurrence, assessed up to 12 months
measure: Overall survival
timeFrame: From date of randomization until the date of death from any cause, assessed up to 36 months
measure: Grade 3-4 adverse effect rate
timeFrame: From date of randomization until the date of death from any cause, assessed up to 3 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Fan Xia, M.D,PH.D
role: PRINCIPAL_INVESTIGATOR
References: