Clinical trial NCT05643417: Camrelizumab Combined With Bevacizumab and HAIC in Patients With Metastatic Liver Cancer Who Failed Standard Therapy
Official title: A Single Center, Multi Cohort, Phase I Basket Trial of the Safety and Efficacy of Camrelizumab in Combination With Bevacizumab and HAIC for Metastatic Liver Cancer After Standard Treatment Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Metastatic Liver Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2022-12-08
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a single center, multi-cohort, phase I basket trial to evaluate the safety and efficacy of camrelizumab in combination with bevacizumab and HAIC for metastatic liver cancer after standard treatment failure

Detailed description: For patients with advanced primary liver cancer, immunotherapy combined anti-angiogenic therapy has gradually become the first-line standard treatment. However, for metastatic liver cancer, especially after first-line treatment failure, the current treatment options are mostly systemic chemotherapy, and there is still a lack of effective treatment methods. Compared with systemic chemotherapy, HAIC has a higher objective response rate and survival rate, and the incidence of adverse reactions is lower. At the same time, PD-1 combined with chemotherapy has become the first-line standard treatment for many cancers; referring to the expert consensus on liver metastasis of solid tumors and ongoing clinical research, the "PD-1 + anti-angiogenesis + HAIC" regimen can be used as a new research direction for posterior treatment for metastatic liver cancer.

In view of the failure of first-line chemotherapy, how to find effective chemotherapy drugs has become a top priority. HAIC guided by genetic testing may be able to screen out effective chemotherapy drugs

This study is an open-label, single-center, multi-cohort, phase I basket trial designed to explore safety and efficacy of "camrelizumab + bevacizumab + HAIC guided by genetic testing" for metastatic liver cancer after standard treatment failure

Eligibility criteria: Inclusion Criteria:

1. Informed consent has been signed
2. Age ≥ 18 years old
3. Liver metastases of solid tumors confirmed by histology or cytology (including but not limited to gastric cancer, breast cancer, lung cancer, nasopharyngeal cancer, thyroid cancer, melanoma, stromal tumor, sarcoma, etc.), including liver metastases at the time of diagnosis or liver metastases occurred after radical resection, and the primary tumor has been resected
4. The investigator assessed that the liver metastasis could not be removed surgically
5. Progression or intolerance after receiving standard systemic therapy (patients who have received first-line immunotherapy can still be enrolled)
6. Child-Pugh score ≤ 7
7. At least one measurable lesion (according to RECIST 1.1)
8. Expected overall survival ≥ 3 months
9. ECOG PS score: 0\~1
10. Has sufficient organ function within 14 days before the first administration, (1) Blood routine: WBC≥3.0×109/L; ANC≥1.5×109/L; PLT≥50×109/L; HGB≥90 g/L (2) Liver function: AST≤5.0×ULN; ALT≤5.0×ULN; TBIL≤2.0×ULN (3) Renal function: Cr≤1.5×ULN or CrCl ≥60 mL/min (4) Coagulation function: INR≤1.5; APTT≤1.5×ULN (5) HBV-DNA≤2×103 IU/ml (subjects with HBV-DNA\>2×103 IU/ml can be enrolled and should receive antiviral treatment at the same time)
11. Women of childbearing age must take contraceptive measures within 3 months from the first dose to the last use of the study drug

Exclusion Criteria:

1. Patients had other malignant tumors in the past or at the same time (excluding non melanoma skin cancer, cervical carcinoma in situ, papillary thyroid cancer after treatment)
2. Patients had a history of organ transplantation or hepatic encephalopathy
3. Suffering from immunodeficiency disease within 7 days before the first administration, or receiving systemic hormone treatment (≥ 10mg/day prednisone or equivalent dose of other hormones), or other forms of immunosuppressive treatment
4. Patients who are seriously allergic to iodized contrast agents, antibody drugs, calcium folinate, 5-FU, platinum drugs , (≥ grade 3)
5. Participated in other clinical trials or received other test drugs within 4 weeks before the first administration
6. Pregnant or lactating women or women of childbearing age are positive in the baseline pregnancy test
7. Other factors that may affect the subject's safety or test compliance as judged by the investigator

Primary outcomes:
measure: Incidence and degree of Adverse Events and Serious Adverse Events
timeFrame: 24 months
measure: ORR
timeFrame: 24 months
Secondary outcomes:
measure: DCR
timeFrame: 24 months
measure: PFS
timeFrame: 24 months
measure: OS
timeFrame: 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Lu Wang
role: PRINCIPAL_INVESTIGATOR
References: