Camrelizumab Combined With Bevacizumab and HAIC in Patients With Metastatic Liver Cancer Who Failed Standard Therapy

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Liver Cancer
• Intervention / Treatment: Drug: HAIC、Bevacizumab、Camrelizumab

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

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Li Tan; Phone Number: 15800680751; Email: 121176421@qq.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200062
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liver metastasis of gastric cancer; HAIC: refer to genetic test results，D1； Bevacizumab：7.5mg/Kg, D2, Q3W；Camrelizumab：200mg, D2, Q3W；	Drug: HAIC、Bevacizumab、Camrelizumab; HAIC: refer to genetic test results，D1 Bevacizumab：7.5mg/Kg, D2, Q3W Camrelizumab：200mg, D2, Q3W; Other Names: Camrelizumab brand name: ai rui ka; Bevacizumab brand name: ai rui tuo
Experimental: Liver metastasis of breast cancer; HAIC: refer to genetic test results，D1；Bevacizumab：7.5mg/Kg, D2, Q3W；Camrelizumab：200mg, D2, Q3W；	Drug: HAIC、Bevacizumab、Camrelizumab; HAIC: refer to genetic test results，D1 Bevacizumab：7.5mg/Kg, D2, Q3W Camrelizumab：200mg, D2, Q3W; Other Names: Camrelizumab brand name: ai rui ka; Bevacizumab brand name: ai rui tuo
Experimental: Liver metastasis of lung cancer; HAIC: refer to genetic test results，D1；Bevacizumab：7.5mg/Kg, D2, Q3W；Camrelizumab：200mg, D2, Q3W；	Drug: HAIC、Bevacizumab、Camrelizumab; HAIC: refer to genetic test results，D1 Bevacizumab：7.5mg/Kg, D2, Q3W Camrelizumab：200mg, D2, Q3W; Other Names: Camrelizumab brand name: ai rui ka; Bevacizumab brand name: ai rui tuo
Experimental: Liver metastasis of nasopharyngeal carcinoma; HAIC: refer to genetic test results，D1；Bevacizumab：7.5mg/Kg, D2, Q3W；Camrelizumab：200mg, D2, Q3W；	Drug: HAIC、Bevacizumab、Camrelizumab; HAIC: refer to genetic test results，D1 Bevacizumab：7.5mg/Kg, D2, Q3W Camrelizumab：200mg, D2, Q3W; Other Names: Camrelizumab brand name: ai rui ka; Bevacizumab brand name: ai rui tuo
Experimental: Liver metastasis of thyroid cancer; HAIC: refer to genetic test results，D1；Bevacizumab：7.5mg/Kg, D2, Q3W；Camrelizumab：200mg, D2, Q3W；	Drug: HAIC、Bevacizumab、Camrelizumab; HAIC: refer to genetic test results，D1 Bevacizumab：7.5mg/Kg, D2, Q3W Camrelizumab：200mg, D2, Q3W; Other Names: Camrelizumab brand name: ai rui ka; Bevacizumab brand name: ai rui tuo
Experimental: Liver metastasis of melanoma; HAIC: refer to genetic test results，D1；Bevacizumab：7.5mg/Kg, D2, Q3W；Camrelizumab：200mg, D2, Q3W；	Drug: HAIC、Bevacizumab、Camrelizumab; HAIC: refer to genetic test results，D1 Bevacizumab：7.5mg/Kg, D2, Q3W Camrelizumab：200mg, D2, Q3W; Other Names: Camrelizumab brand name: ai rui ka; Bevacizumab brand name: ai rui tuo
Experimental: Liver metastasis of stromal tumor; HAIC: refer to genetic test results，D1；Bevacizumab：7.5mg/Kg, D2, Q3W；Camrelizumab：200mg, D2, Q3W；	Drug: HAIC、Bevacizumab、Camrelizumab; HAIC: refer to genetic test results，D1 Bevacizumab：7.5mg/Kg, D2, Q3W Camrelizumab：200mg, D2, Q3W; Other Names: Camrelizumab brand name: ai rui ka; Bevacizumab brand name: ai rui tuo
Experimental: Liver metastasis of sarcoma; HAIC: refer to genetic test results，D1；Bevacizumab：7.5mg/Kg, D2, Q3W；Camrelizumab：200mg, D2, Q3W；	Drug: HAIC、Bevacizumab、Camrelizumab; HAIC: refer to genetic test results，D1 Bevacizumab：7.5mg/Kg, D2, Q3W Camrelizumab：200mg, D2, Q3W; Other Names: Camrelizumab brand name: ai rui ka; Bevacizumab brand name: ai rui tuo
Experimental: Liver metastasis of other solid tumor; HAIC: refer to genetic test results，D1；Bevacizumab：7.5mg/Kg, D2, Q3W；Camrelizumab：200mg, D2, Q3W；	Drug: HAIC、Bevacizumab、Camrelizumab; HAIC: refer to genetic test results，D1 Bevacizumab：7.5mg/Kg, D2, Q3W Camrelizumab：200mg, D2, Q3W; Other Names: Camrelizumab brand name: ai rui ka; Bevacizumab brand name: ai rui tuo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and degree of Adverse Events and Serious Adverse Events	Incidence, severity, and relationship to study drugs of all adverse events (AEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs).	24 months
ORR	objective response rate(ORR)，defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DCR	disease control rate(DCR), defined as the percentage of participants who have a confirmed complete response（CR） or partial response（PR） or stable disease（SD） per RECIST 1.1 as assessed by investigator	24 months
PFS	progression-free survival(PFS), defined as the time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator	24 months
OS	overall survival(OS), defined as the time from enrollment to death due to any cause.	24 months

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Lu Wang, Fudan University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: November 20, 2022
• First Submitted That Met QC Criteria: December 7, 2022
• First Posted (Estimate): December 8, 2022

Study Record Updates

• Last Update Posted (Estimate): December 8, 2022
• Last Update Submitted That Met QC Criteria: December 7, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: 22-OBU-SH-CA-II-019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No