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

Primary Purpose

Metastatic Liver Cancer

Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
HAIC、Bevacizumab、Camrelizumab
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Liver Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Informed consent has been signed Age ≥ 18 years old 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 The investigator assessed that the liver metastasis could not be removed surgically Progression or intolerance after receiving standard systemic therapy (patients who have received first-line immunotherapy can still be enrolled) Child-Pugh score ≤ 7 At least one measurable lesion (according to RECIST 1.1) Expected overall survival ≥ 3 months ECOG PS score: 0~1 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) 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: 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) Patients had a history of organ transplantation or hepatic encephalopathy 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 Patients who are seriously allergic to iodized contrast agents, antibody drugs, calcium folinate, 5-FU, platinum drugs , (≥ grade 3) Participated in other clinical trials or received other test drugs within 4 weeks before the first administration Pregnant or lactating women or women of childbearing age are positive in the baseline pregnancy test Other factors that may affect the subject's safety or test compliance as judged by the investigator

Sites / Locations

  • Fudan University Shanghai Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Liver metastasis of gastric cancer

Liver metastasis of breast cancer

Liver metastasis of lung cancer

Liver metastasis of nasopharyngeal carcinoma

Liver metastasis of thyroid cancer

Liver metastasis of melanoma

Liver metastasis of stromal tumor

Liver metastasis of sarcoma

Liver metastasis of other solid tumor

Arm Description

HAIC: refer to genetic test results,D1; Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;

HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;

HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;

HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;

HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;

HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;

HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;

HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;

HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;

Outcomes

Primary Outcome Measures

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).
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.

Secondary Outcome Measures

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
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
OS
overall survival(OS), defined as the time from enrollment to death due to any cause.

Full Information

First Posted
November 20, 2022
Last Updated
December 7, 2022
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT05643417
Brief Title
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

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 2022 (Anticipated)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Liver Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Liver metastasis of gastric cancer
Arm Type
Experimental
Arm Description
HAIC: refer to genetic test results,D1; Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;
Arm Title
Liver metastasis of breast cancer
Arm Type
Experimental
Arm Description
HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;
Arm Title
Liver metastasis of lung cancer
Arm Type
Experimental
Arm Description
HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;
Arm Title
Liver metastasis of nasopharyngeal carcinoma
Arm Type
Experimental
Arm Description
HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;
Arm Title
Liver metastasis of thyroid cancer
Arm Type
Experimental
Arm Description
HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;
Arm Title
Liver metastasis of melanoma
Arm Type
Experimental
Arm Description
HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;
Arm Title
Liver metastasis of stromal tumor
Arm Type
Experimental
Arm Description
HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;
Arm Title
Liver metastasis of sarcoma
Arm Type
Experimental
Arm Description
HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;
Arm Title
Liver metastasis of other solid tumor
Arm Type
Experimental
Arm Description
HAIC: refer to genetic test results,D1;Bevacizumab:7.5mg/Kg, D2, Q3W;Camrelizumab:200mg, D2, Q3W;
Intervention Type
Drug
Intervention Name(s)
HAIC、Bevacizumab、Camrelizumab
Other Intervention Name(s)
Camrelizumab brand name: ai rui ka; Bevacizumab brand name: ai rui tuo
Intervention Description
HAIC: refer to genetic test results,D1 Bevacizumab:7.5mg/Kg, D2, Q3W Camrelizumab:200mg, D2, Q3W
Primary Outcome Measure Information:
Title
Incidence and degree of Adverse Events and Serious Adverse Events
Description
Incidence, severity, and relationship to study drugs of all adverse events (AEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs).
Time Frame
24 months
Title
ORR
Description
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.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
DCR
Description
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
Time Frame
24 months
Title
PFS
Description
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
Time Frame
24 months
Title
OS
Description
overall survival(OS), defined as the time from enrollment to death due to any cause.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Informed consent has been signed Age ≥ 18 years old 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 The investigator assessed that the liver metastasis could not be removed surgically Progression or intolerance after receiving standard systemic therapy (patients who have received first-line immunotherapy can still be enrolled) Child-Pugh score ≤ 7 At least one measurable lesion (according to RECIST 1.1) Expected overall survival ≥ 3 months ECOG PS score: 0~1 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) 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: 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) Patients had a history of organ transplantation or hepatic encephalopathy 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 Patients who are seriously allergic to iodized contrast agents, antibody drugs, calcium folinate, 5-FU, platinum drugs , (≥ grade 3) Participated in other clinical trials or received other test drugs within 4 weeks before the first administration Pregnant or lactating women or women of childbearing age are positive in the baseline pregnancy test Other factors that may affect the subject's safety or test compliance as judged by the investigator
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Li Tan
Phone
15800680751
Email
121176421@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lu Wang
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200062
Country
China

12. IPD Sharing Statement

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

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