Colorectal Liver Metastasis
Conditions
Brief summary
Pts with histologically confirmed CRLM and whose CRS \>2 were enrolled into this single-arm, phase II study. The critical enrollment criteria were that Subjects had completely resected Primary lesion and liver metastases and had no evidence of extrahepatic disease. After hepatectomy， HAIC (FOLFOX: oxaliplatin 85mg/m2, 5- fluorouracil 2500mg/m2, calcium folinate 400mg/m2) was given every 4-6 weeks for 2-4 cycles depending on pts' health status, in combination with Sintilimab (200mg, iv, d1) and regorafenib (80mg, po, d1-21) every 3 weeks for up to 6 months. The primary endpoint was 1-year recurrence-free survival (RFS) and secondary endpoints included RFS, overall survival (OS), safety, and health-related quality of life.
Interventions
COMBINATION_PRODUCTHAIC-FOLFOX combined with Sintilimab and Regorafenib
HAIC (FOLFOX: oxaliplatin 85mg/m2, 5- fluorouracil 2500mg/m2, calcium folinate 400mg/m2) was given every 4-6 weeks for 2-4 cycles depending on pts' health status, in combination with Sintilimab (200mg, iv, d1) and regorafenib (80mg, po, d1-21) every 3 weeks for up to 6 months .
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged over 18 years， men or women who are not pregnant； 2. ECOG PS 0/1 evaluated 14 days before enrollment, and expected survival \>12 months after liver resection; 3. Liver function: Child-Pugh score Class A or ≤7 Class B； 4. Patients with histologically- or clinically-confirmed CRLM（TxNxM1）and CRS\>2； 5. Patients had completely resected Primary lesions and liver metastases as well as no evidence of extrahepatic disease； 6. No complications such as bleeding, jaundice, infection, abdominal pleural effusion, obstruction and perforation were observed within 7 days (including 7 days) before the screening. The subjects recovered well after surgery, the surgical incision healed well, the stitches were removed, and the drainage tube was removed; 7. Preoperative chemoradiotherapy was limited to neoadjuvant or conversion therapy； 8. Patients must have the ability to understand and voluntarily sign the informed consent, and must sign an informed consent before starting any specific procedure for the study； 9. Patients were considered capable of complying with the study protocol； 10. No medical comorbidities that could interfere with chemotherapy and immunotherapy or targeted therapy, see
Exclusion criteria
； 11. Pre-treatment tumour tissue sample (if available). If tumour tissue is available, submit one formalin-fixed, paraffin-embedded (FFPE) tumour sample from a paraffin block (preferred), or approximately 10-15 slides containing unstained, freshly cut, serial sections, along with a relevant pathology report within 4 weeks of enrollment. If the FFPE samples described above are not available, any type of sample (including fine needle aspiration biopsy samples, cell mass samples \[e.g., samples from pleural effusion\] and lavage samples) may also be accepted. An associated pathology report should be provided with the sample. If tumour tissue is not available (e.g., exhausted due to past diagnostic tests), subjects are still eligible for study participation; 12. Adequate haematological and organ function， based on the following laboratory results obtained during the 14 days prior to enrollment (unless otherwise stated) ： Absolute neutrophil count (ANC)≥1.5×10 9 /L (1500/μL)， without supported granulocyte colony-stimulating factor Lymphocyte count ≥0.5×10 9 /L (500/μL) Platelets ≥ 75 × 10 9 /L（75, 000/μL） Haemoglobin≥ 85 g/L, blood transfusions may be permitted to meet this criterion Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) ≤ 5 × upper limit of normal (ULN); Serum bilirubin≤ 3 × ULN Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥50 mL/min (using Cockcroft-Gault formula) Serum albumin≥28 g/L（2.8 g/dL） INR or aPTT≤2 × ULN, or PT prolonged ≤ 3 s if patients did not receive anticoagulant therapy. Albuminuria \< 2+ tested by urinary cellulose (carried out within 14 days prior to initiation of treatment); Patients with baseline albuminuria ≥2+ should have their urine collected for 24 hours and must then confirm that albuminuria content within 24 hours is \< 1g. 13. Any acute, clinically significant treatment-related toxicity (due to prior treatment) must have resolved to ≤ grade 1 prior to enrollment, except for hair loss; 14. HIV antibody test results were negative at screening; 15. Patients with active hepatitis B virus (HBV) infection: HBVDNA \< 2000IU/mL acquired within 28 days prior to enrollment, receiving anti-HBV therapy (in accordance with local standard care, such as Entecavir) for at least 7 days prior to enrollment and willing to continue treatment during the study period; Patients with active hepatitis C virus (HCV) infection: HCVRNA \< 2000IU/mL acquired within 28 days prior to enrollment, receiving anti-HCV therapy for at least 7 days prior to enrollment and willing to continue treatment during the study; 16. Women of childbearing age must undergo a negative pregnancy test (βHCG) before treatment, and women of childbearing age and men (who have sex with women of childbearing age) must agree to use effective contraception uninterrupted during treatment and for six months after the last therapeutic dose was administered.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-year recurrence-free survival rate (1-year RFS) | 12 months | Incidence of recurrence-free patients in one year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| recurrence-free survival (RFS) | Up to approximately 2 years | time from surgery to recurrence or death |
| overall survival (OS) | Up to approximately 5 years | time from enrollment to death |
| Safety and tolerability | Up to approximately 2 years | adverse effect，Incidence of Adverse Events and Treatment-Emergent Adverse Events \[Safety and Tolerability\] |
| health-related quality of life (HRQol) | Up to approximately 2 years | using patient-reported outcomes(PROs) via The European Organisation for Research and Treatment of Cancer(EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30) |
Countries
China
Contacts
Primary ContactLu Wang, M.D.
Outcome results
None listed