Colorectal Cancer, Immunotherapy, Liver Metastases, Radiotherapy
Conditions
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.
Interventions
RADIATIONSBRT
postoperative SBRT of liver lesions
DRUGChemotherapy
XELOX/FOLFOX/FOLFIRI
DRUGPD-1 antibody
Sintilimab (200mg d1，q3w)
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
adjuvant radiotherapy: SBRT; immunotherapy: sintilimab chemotherapy: XELOX
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
Countries
China
Contacts
Primary ContactFan Xia, M.D, PH.D
Outcome results
None listed