Clinical trial
Targeted Treatment Based on ctDNA Genotyping Combined With Tislelizumab and HAIC as Salvage Treatment for Advanced Colorectal Cancer Liver Metastasis Failed From Standard Systemic Treatment (SALVLIV Trial)
Name
PekingUCHI
Description
Hepatic arterial infuison chemothearpy (HAIC), targeted therapy, and programmed death-1 (PD-1) inhibitors have been demonstrated to be effective for colorectal cancer liver metastasis (CRCLM). Thus, the investigators will conduct a prospective trial to explore the efficacy and safety of targeted treatment based on ctDNA genotyping combined with tislelizumab and HAIC as salvage treatment for advanced CRCLM failed from standard systemic treatment, aiming to provide individualized optimized regimen for microsatellite stable (MSS) CRCLM in salvage treatment.
Trial arms
Trial start
2024-01-23
Estimated PCD
2026-01-23
Trial end
2027-01-23
Status
Recruiting
Treatment
HAIC+targeted therapy+PD-1 inhibitor
HAIC regimen: doublet or triplet regimen based on the response and adverse events occurred in the previous standard treatment (depended on the decision of researchers)-oxaliplatin (85 mg/m2, split into d1 and d2, 0-2h,) and 5-fluorouracial (2g/m2, split into d1 and d2, 2-24h)/ oxaliplatin (65 mg/m2, 0-2h, d1), irinotecan (100 mg/m2, 0-2h, d2), and 5-fluorouracial (2g/m2, split in d1 and d2, 2-24h), repeated every 4 weeks; drug-eluting TACE will be performed at 3rd-4th cycles if the lesions in liver is abundant with blood supply.
Tislelizumab (a PD-1 inhibitor): 200 mg, intravenous drip for 30-60 minutes before 24h of HAIC, q4w.
Cetuximab (Group A, KRAS/NRAK/BRAF/EGFR wide type and interrupt cetuximab more than 3 months): 500 mg/m2, intravenous drip before HAIC, q4w.
Fruquintinib (Group B, KRAS/NRAS/BRAF/EGFR mutation type and wide type but treated with cetuximab in last 3 months): 3 mg/d, d3-23, then suspend for 1w.
Arms:
Treatment Arm
Other names:
HAIC+Fruquintinib/Cetuximab+Tislelizumab
Size
47
Primary endpoint
PFS rate at 6 months
From the date of treatment begining to the date of 6 months after the treatment begining.
Eligibility criteria
Inclusion Criteria:
1. 18-80 years old.
2. Colorectal cancer confirmed by histopatology.
3. The metastasis is mainly located in liver.
4. Unresectable liver metastasis is confirmed by CT/MRI scan and multidisciplinary.
5. Failed from standard first- and second-line systemic treatment.
6. At least one measurable lesion according to modified Response Evaluation Criteria in Solid Tumors guidelines (mRECIST).
7. Eastern Cooperative Oncology Group (ECOG) performance status \<2.
8. Child-Pugh A or B (≤ 7).
9. Expectant survival time ≥ 3 months.
10. Adequate organ function as follows:
1. Hemoglobin ≥ 90 g/L;
2. Absolute neutrophil count ≥ 1.5×10\^9/L;
3. Blood platelet count ≥ 775×10\^9/L;
4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 5 times of upper limit of normal (ULN);
5. Total bilirubin ≤ 2 times of ULN;
6. Serum creatinine ≤ 1.5 times of ULN;
7. Albumin ≥ 30 g/L.
11. Patients sign informed consent.
Exclusion Criteria:
1. Extensive extrahepatic metastasis (\>25% of tumor burden in liver).
2. HER2 (3+) or HER2 amplification.
3. MSI-H or dMMR.
4. Allergic to contrast media.
5. Pregnant or lactational.
6. Allergic to oxaliplatin or cetuximab.
7. Coinstantaneous a lot of malignant hydrothorax or ascites.
8. History of organ transplantation (including bone marrow auto-transplantation and peripheral stem cell transplantation).
9. Coinstantaneous infection and need anti-infection therapy.
10. Coinstantaneous peripheral nervous system disorder.
11. History of obvious mental disorder and central nervous system disorder.
12. Concomitant malignancy within 5 years, except for non-melanoma skin cancer and carcinoma in situ of cervix.
13. Without legal capacity.
14. Impact the study because of medical or ethical reasons.
15. Clinically severe gastrointestinal bleeding within 6 months of the start of treatment or any life-threatening bleeding events within 3 months of the start of treatment.
16. Uncorrectable coagulation disorder.
17. Obvious abnormal in ECG or obvious clinical symptoms of heart disease, like congestive heart failure, coronary heart disease with obvious clinical symptoms, unmanageable arrhythmia and hypertension.
18. History of myocardial infarction within 12 months, or Grade III/IV of heart function.
19. Severe liver disease (like cirrhosis), renal disease, respiratory disease, unmanageable diabetes or other kinds of systematic disease.
20. Any other subjects that the investigator considers ineligible.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 47, 'type': 'ESTIMATED'}}
Updated at
2024-01-25
1 organization
1 product
4 indications
Organization
Peking UniversityIndication
Liver Metastasis Colon CancerIndication
ctDNA GenotypeIndication
MSSIndication
Failed From Standard Treatment