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The Safety and Efficacy of HAIC+Tislelizumab+Regorafenib in Patients With Colorectal Liver Metastases

Primary Purpose

Colorectal Liver Metastases

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tislelizumab
Regorafenib
HAIC
Sponsored by
Peking University Cancer Hospital & Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Liver Metastases

Eligibility Criteria

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

Inclusion Criteria: Age≥18 years old Histologically or cytologically confirmed colorectal cancer with unresectable or surgical contraindicated liver metastases Extrahepatic metastases are allowed and the primary tumor load is assessed to be intrahepatic by two or more attending physicians Whether liver metastases can be resected or not is determined by two or more attending physicians according to the Chinese guidelines for the diagnosis and comprehensive treatment of colorectal liver metastases Patients with unresectable colorectal liver metastases after failed standard second-line therapy Including, but not limited to, Oxaliplatin, Fluorouracil, and Irinotecan Treatment failure is defined as disease progression and intolerable toxicity Patients who withdrew from standard therapy due to unacceptable toxicity, guaranteed to discontinue treatment before disease progression and excluded treatment with the same drug, are also allowed to be included in the study. At least one measurable lesion according to RECIST 1.1 criteria Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 Subject life expectancy ≥12 weeks Laboratory tests of bone marrow, hepatic and renal function and coagulation function within 7 days before the first dose of medication meet the study requirements - No blood transfusion, blood products, or correction with granulocyte colony-stimulating factor or other hematopoietic stimulating factor within 7 days before laboratory testing. Female patients of childbearing age must have a negative blood pregnancy test within 7 days before the first dose of medication and male or female patients of childbearing age volunteered to take effective contraceptive measures during the whole treatment and within 3 months after treatment All patients must sign an informed consent form and follow the trial treatment protocol and follow up plan Exclusion Criteria: ANC <1.5×109/L, or platelet count <80×109/L, or HGB < 9g/dL; - Blood transfusion to meet enrollment criteria within 2 weeks before enrollment is not allowed serum total bilirubin>2.0 times upper limit of normal AST and/or ALT>5.0 times upper limit of normal Serum creatinine>1.5 times upper limit of normal, or creatinine clearance rate<50ml/min(calculated according to the Cockcroft-Gault formula) APTT or PT>1.5 times upper limit of normal Clinically significant severe electrolyte abnormalities by the investigator Urine protein test 2+ or more, or 24 hours urine protein quantitation ≥1.0g/24h Hypertension that is not stably controlled by medications: systolic blood pressure(SBP) >140mmHg or diastolic blood pressure(DBP) > 90mmHg Patients with active gastric and duodenal ulcer, ulcerative colitis or other gastrointestinal diseases or unresected tumors with active bleeding, or other conditions that may cause gastrointestinal bleeding or perforation as judged by the investigators; Or patients with previous gastrointestinal perforation or gastrointestinal fistula, which is not cured after surgical treatment History of arterial or deep-vein thrombosis within 6 months before enrollment or evidence or history of bleeding tendency within 2 months before enrollment, regardless of severity History of troke or transient ischemic attack within 12 months before enrollment History of heart disease within 6 months before enrollment, manifested as congestive heart failure, acute myocardial infarction, severe/unstable angina, coronary artery bypass grafting; impaired cardiac function in NYHA class 2 or above; left ventricular ejection fraction (LVEF) <50% Uncontrolled malignant pleural, ascites, or pericardial effusion - defined as not being effectively controlled with diuretics or punctures Clinically detectable second primary malignancy or history of other malignancies within 5 years. Adequately treated nonmelanoma skin cancers, cervical carcinoma in situ, and superficial bladder tumors [noninvasive tumors, carcinoma in situ, and T1 (tumor invasion of the lamina propria)] are excluded Central nervous system (CNS) metastases or previous brain metastases Clinically uncontrolled severe active infection Pregnant or lactating women or women of childbearing age have a positive pregnancy test before the first dose of medication; Or female participants themselves and their partners who are unwilling to use strict contraception during the trial Patients are considered by the investigator to have any clinical or laboratory abnormalities or compliance issues that precluded participation in the trial Serious psychological or psychiatric abnormalities

Sites / Locations

  • Beijing Cancer HospitalRecruiting
  • Beijing Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HAIC combined with Tislelizumab and Regorafenib

Arm Description

HAIC combined with Tislelizumab and Regorafenib until progression or death.

Outcomes

Primary Outcome Measures

Safety profiles by NCI-CTCAE version 5 .0
The evaluation of adverse events , using NCI-CTCAE version 5.0.

Secondary Outcome Measures

Overall response rate(ORR)
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.
Disease control rate(DCR)
The ORR is defined as the proportion of subjects with confirmed complete response, partial response, or stable disease according to RECIST v 1.1.
Duration of Response (DoR)
The time from the date of first documentation of a partial response or complete response to the date of first documentation of progressive disease (PD) or date of death due to any cause.
Response rate of intrahepatic lesions
Response rate of intrahepatic lesions defined as the proportion of intrahepatic lesions that achieved complete response or partial response, regardless of extrahepatic lesions.
Response rate of extrahepatic lesions
Response rate of extrahepatic lesions defined as the proportion of intrahepatic lesions that achieved complete response or partial response, regardless of intrahepatic lesions.
Quality of Life (QoL)
The patient's ability to perform daily living can be evaluated through specific questionnaire(EORTC QLQ-C30), so as to evaluate the effect of anti-tumor drug treatment.
Overall survival (OS)
Overall survival is defined as the time from the start of HAIC until death due to any cause.
Progression free survival (PFS)
Progression-free survival is defined as the time from the start of HAIC until the first documentation of disease progression or death due to any cause, whichever occurs first.

Full Information

First Posted
January 17, 2023
Last Updated
May 25, 2023
Sponsor
Peking University Cancer Hospital & Institute
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1. Study Identification

Unique Protocol Identification Number
NCT05877001
Brief Title
The Safety and Efficacy of HAIC+Tislelizumab+Regorafenib in Patients With Colorectal Liver Metastases
Official Title
An Open Label, Single-center Study on the Safety of Hepatic Arterial Infusion Chemotherapy Combined With Tislelizumab and Regorafenib in Patients With Advanced Treated Colorectal Liver Metastases
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 30, 2023 (Anticipated)
Primary Completion Date
July 30, 2024 (Anticipated)
Study Completion Date
March 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking University Cancer Hospital & Institute

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
Tislelizumab is an anti-PD-1 monoclonal antibody with high binding affinity for PD-1 and with minimized Fcγ receptor binding on macrophages. Regorafenib has been approved in mCRC by CFDA. Hepatic arterial infusion chemotherapy has a high local control rate for liver metastases. NCCN guidelines and several expert consensus recommend that regional hepatic arterial infusion chemotherapy can be considered as a "rescue treatment" for patients with colorectal cancer liver metastases who fail to receive first-line or second-line systemic chemotherapy, which can significantly prolong the overall survival of patients.
Detailed Description
The investigators aimed to evaluated the safety and efficacy of HAIC combined with Tislelizumab and Regorafenib in patients with advanced treated colorectal liver metastases. This study is a prospective, open label, single-center clinical study and the sample size is 20.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Liver Metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HAIC combined with Tislelizumab and Regorafenib
Arm Type
Experimental
Arm Description
HAIC combined with Tislelizumab and Regorafenib until progression or death.
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Other Intervention Name(s)
BGB-A317
Intervention Description
200mg, IV, Q3W
Intervention Type
Drug
Intervention Name(s)
Regorafenib
Other Intervention Name(s)
BAY73-4506
Intervention Description
80 mg once daily for the first 3 weeks of each 4-week cycle
Intervention Type
Other
Intervention Name(s)
HAIC
Intervention Description
OXA 85mg/m2 IA 0-4h +5-Fu 2000mg/m2 IA 4-48h,CF 200mg/m2 IV 2-4h, Q3W
Primary Outcome Measure Information:
Title
Safety profiles by NCI-CTCAE version 5 .0
Description
The evaluation of adverse events , using NCI-CTCAE version 5.0.
Time Frame
From the first patient enrolled to 15 months after the last patient enrolled.
Secondary Outcome Measure Information:
Title
Overall response rate(ORR)
Description
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.
Time Frame
up to 2 years
Title
Disease control rate(DCR)
Description
The ORR is defined as the proportion of subjects with confirmed complete response, partial response, or stable disease according to RECIST v 1.1.
Time Frame
Up to 2 years
Title
Duration of Response (DoR)
Description
The time from the date of first documentation of a partial response or complete response to the date of first documentation of progressive disease (PD) or date of death due to any cause.
Time Frame
Up to 2 years
Title
Response rate of intrahepatic lesions
Description
Response rate of intrahepatic lesions defined as the proportion of intrahepatic lesions that achieved complete response or partial response, regardless of extrahepatic lesions.
Time Frame
Up to 2 years
Title
Response rate of extrahepatic lesions
Description
Response rate of extrahepatic lesions defined as the proportion of intrahepatic lesions that achieved complete response or partial response, regardless of intrahepatic lesions.
Time Frame
Up to 2 years
Title
Quality of Life (QoL)
Description
The patient's ability to perform daily living can be evaluated through specific questionnaire(EORTC QLQ-C30), so as to evaluate the effect of anti-tumor drug treatment.
Time Frame
Up to 2 years
Title
Overall survival (OS)
Description
Overall survival is defined as the time from the start of HAIC until death due to any cause.
Time Frame
Up to 2 years
Title
Progression free survival (PFS)
Description
Progression-free survival is defined as the time from the start of HAIC until the first documentation of disease progression or death due to any cause, whichever occurs first.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age≥18 years old Histologically or cytologically confirmed colorectal cancer with unresectable or surgical contraindicated liver metastases Extrahepatic metastases are allowed and the primary tumor load is assessed to be intrahepatic by two or more attending physicians Whether liver metastases can be resected or not is determined by two or more attending physicians according to the Chinese guidelines for the diagnosis and comprehensive treatment of colorectal liver metastases Patients with unresectable colorectal liver metastases after failed standard second-line therapy Including, but not limited to, Oxaliplatin, Fluorouracil, and Irinotecan Treatment failure is defined as disease progression and intolerable toxicity Patients who withdrew from standard therapy due to unacceptable toxicity, guaranteed to discontinue treatment before disease progression and excluded treatment with the same drug, are also allowed to be included in the study. At least one measurable lesion according to RECIST 1.1 criteria Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 Subject life expectancy ≥12 weeks Laboratory tests of bone marrow, hepatic and renal function and coagulation function within 7 days before the first dose of medication meet the study requirements - No blood transfusion, blood products, or correction with granulocyte colony-stimulating factor or other hematopoietic stimulating factor within 7 days before laboratory testing. Female patients of childbearing age must have a negative blood pregnancy test within 7 days before the first dose of medication and male or female patients of childbearing age volunteered to take effective contraceptive measures during the whole treatment and within 3 months after treatment All patients must sign an informed consent form and follow the trial treatment protocol and follow up plan Exclusion Criteria: ANC <1.5×109/L, or platelet count <80×109/L, or HGB < 9g/dL; - Blood transfusion to meet enrollment criteria within 2 weeks before enrollment is not allowed serum total bilirubin>2.0 times upper limit of normal AST and/or ALT>5.0 times upper limit of normal Serum creatinine>1.5 times upper limit of normal, or creatinine clearance rate<50ml/min(calculated according to the Cockcroft-Gault formula) APTT or PT>1.5 times upper limit of normal Clinically significant severe electrolyte abnormalities by the investigator Urine protein test 2+ or more, or 24 hours urine protein quantitation ≥1.0g/24h Hypertension that is not stably controlled by medications: systolic blood pressure(SBP) >140mmHg or diastolic blood pressure(DBP) > 90mmHg Patients with active gastric and duodenal ulcer, ulcerative colitis or other gastrointestinal diseases or unresected tumors with active bleeding, or other conditions that may cause gastrointestinal bleeding or perforation as judged by the investigators; Or patients with previous gastrointestinal perforation or gastrointestinal fistula, which is not cured after surgical treatment History of arterial or deep-vein thrombosis within 6 months before enrollment or evidence or history of bleeding tendency within 2 months before enrollment, regardless of severity History of troke or transient ischemic attack within 12 months before enrollment History of heart disease within 6 months before enrollment, manifested as congestive heart failure, acute myocardial infarction, severe/unstable angina, coronary artery bypass grafting; impaired cardiac function in NYHA class 2 or above; left ventricular ejection fraction (LVEF) <50% Uncontrolled malignant pleural, ascites, or pericardial effusion - defined as not being effectively controlled with diuretics or punctures Clinically detectable second primary malignancy or history of other malignancies within 5 years. Adequately treated nonmelanoma skin cancers, cervical carcinoma in situ, and superficial bladder tumors [noninvasive tumors, carcinoma in situ, and T1 (tumor invasion of the lamina propria)] are excluded Central nervous system (CNS) metastases or previous brain metastases Clinically uncontrolled severe active infection Pregnant or lactating women or women of childbearing age have a positive pregnancy test before the first dose of medication; Or female participants themselves and their partners who are unwilling to use strict contraception during the trial Patients are considered by the investigator to have any clinical or laboratory abnormalities or compliance issues that precluded participation in the trial Serious psychological or psychiatric abnormalities
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xu Zhu, MD
Phone
+86-10-88196001
Email
drzhuxu@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Feng Aiwei, MD
Phone
+86-10-88196330
Email
ivyfeng_1026@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xu Zhu, MD
Organizational Affiliation
Peking University Cancer Hospital & Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhu Xu, M.D.
Phone
0086-10-88196330
Email
zhux387@263.net
First Name & Middle Initial & Last Name & Degree
Aiwei Feng, M.D.
Phone
0086-10-88196330
Email
ivyfeng_1026@163.com
First Name & Middle Initial & Last Name & Degree
Zhu Xu, M.D.
Facility Name
Beijing Cancer Hospital
City
Beijing
ZIP/Postal Code
100142
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xu Zhu, M.D.
Phone
861088196330
Email
drzhuxu@163.com
First Name & Middle Initial & Last Name & Degree
Aiwei Feng, M.D.
Phone
861088196330
Email
ivyfeng_1026@163.com

12. IPD Sharing Statement

Learn more about this trial

The Safety and Efficacy of HAIC+Tislelizumab+Regorafenib in Patients With Colorectal Liver Metastases

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