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Serplulimab+Regorafenib +Hepatic Artery Bicarbonate Infusion in Patients With Colorectal Cancer and Liver Metastases

Primary Purpose

Colorectal Cancer, Liver Metastases

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Serplulimab+Regorafenib
Hepatic Artery Bicarbonate Infusion
Sponsored by
Second Affiliated Hospital, School of Medicine, Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring Colorectal Cancer, Regorafenib, hepatic artery bicarbonate infusion, Serplulimab

Eligibility Criteria

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

Inclusion Criteria: Age 18 or above, male or female; Patients with colorectal cancer and liver metastases who strictly conform to the clinical diagnostic criteria of "Chinese Guidelines for Diagnosis and Treatment of Colorectal Cancer (2020 Edition)" or who have been confirmed by histopathology or cytology; At least 1 measurable intrahepatic lesion; Child-Pugh liver function rating: A or good B (≤7 points) ; No local treatment including radiotherapy, surgical excision and ablation was performed before interventional therapy; No other malignant tumors; ECOG score within one week before enrollment: 0-1; Predicted survival ≥24 weeks; The major organs are functioning normally; the following criteria are met: Blood examination: a) HB≥90 g/L;b) ANC≥1.5×109/L;c) PLT≥80×109/L; Biochemical examination: a) ALB ≥29 g/L;b) ALT and AST<5ULN;c) TBIL ≤1.5ULN;d) Creatinine≤1.5ULN;(Only one of the two measures of albumin and bilirubin in the Child-Pugh rating can be a score of 2); Thyroid function tests are within normal range; Women of childbearing age must already be using reliable contraception or have had a pregnancy test (serum or urine) with negative results within 7 days prior to inclusion and be willing to use an appropriate method of contraception during the trial period and 8 weeks after the last test drug administration; The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up; Exclusion Criteria: There is a contraindication of anti-PD-1 monoclonal antibody therapy; With other uncured malignancies, except for cured basal cell carcinoma of the skin and cervical carcinoma in situ; Patients who are preparing for an organ transplant or have had an organ transplant in the past; Ascites with clinical symptoms that require therapeutic abdominal puncture or drainage, or Child-Pugh score > 2; Patients with high blood pressure (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg) who cannot be reduced to the normal range by antihypertensive medication; Patients with grade Ⅱ or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval ≥450 ms for males and 470 ms for females); A history of symptomatic ischemic or hemorrhagic cerebrovascular disease; Having multiple factors that affect oral medication (such as inability to swallow, chronic diarrhea, and intestinal obstruction, which significantly affects drug administration and absorption); Patients with a history of gastrointestinal bleeding or a definite tendency to gastrointestinal bleeding within the past 6 months, such as esophageal varicose veins with bleeding risk, locally active ulcer lesions, stool occult blood ≥ (++), should not be included in the group; If fecal occult blood (+), gastroscopy is required; Had an abdominal fistula, gastrointestinal perforation, or abdominal abscess in the 28 days prior to joining the study; Patients with abnormal coagulation function (INR > 1.5 or prothrombin time (PT) > ULN+4 seconds) who are prone to bleeding or are receiving thrombolytic or anticoagulant therapy; Patients with central nervous system metastases or known brain metastases; Patients with past and current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, and severe impairment of lung function; Urine routine showed urine protein ≥++ or confirmed 24 hours urine protein quantity > 1.0 g; Severe thyroid disease cannot be controlled by treatment; Rheumatic or autoimmune diseases, and immunosuppressant or high-dose hormone therapy after organ transplantation;

Sites / Locations

  • the Second Affiliated Hospital of Medical College of Zhejiang University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Serplulimab in combination with Regorafenib and hepatic artery bicarbonate infusion

Arm Description

Serplulimab: once every two weeks; Regorafenib: from the first day to the 21th day; hepatic artery bicarbonate infusion: once every four weeks

Outcomes

Primary Outcome Measures

Objective Response Rate
Objective Response Rate was defined as the proportion of patients with a best objective response of complete response (CR) or partial response (PR) according to RECIST criteria (version 1.1).

Secondary Outcome Measures

Adverse Events and Serious Adverse Events
Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0.
Progression free survival
Progression-free survival is defined as the time from enrollment to the first documented disease progression according to RECIST version 1.1, or to death from any cause, whichever occurred first
Overal survival
Time from randomization to death (from any cause)

Full Information

First Posted
May 31, 2023
Last Updated
June 7, 2023
Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
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1. Study Identification

Unique Protocol Identification Number
NCT05894837
Brief Title
Serplulimab+Regorafenib +Hepatic Artery Bicarbonate Infusion in Patients With Colorectal Cancer and Liver Metastases
Official Title
Serplulimab in Combination With Regorafenib and Hepatic Artery Bicarbonate Infusion for Third-line Treatment in Patients With Colorectal Cancer and Liver Metastases: a Single-center, Single-arm, Phase 2 Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 1, 2023 (Anticipated)
Primary Completion Date
June 1, 2024 (Anticipated)
Study Completion Date
June 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University

4. Oversight

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

5. Study Description

Brief Summary
A single-center, single-arm, phase 2 trial of Serplulimab in combination with Regorafenib and hepatic artery bicarbonate infusion for third-line treatment in patients with colorectal cancer and liver metastases. A total of 30 patients are planned to be enrolled.
Detailed Description
This is a single-center, single-arm, phase 2 trial. Enroll 30 patients with colorectal cancer and liver metastases and failure of standard therapy. Administer serplulimab intravenously(once every two weeks)in combination with regorafenib(from the first day to the 21th day) and hepatic artery bicarbonate infusion (once every four weeks). Medication must be discontinued until disease progression, intolerable toxicity, informed consent is withdrawn, or investigator judgment is made. The primary endpoint is objective response rate (ORR), and secondary endpoints are progression-free survival (PFS), overall survival (OS), and adverse effects (AE).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Liver Metastases
Keywords
Colorectal Cancer, Regorafenib, hepatic artery bicarbonate infusion, Serplulimab

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Serplulimab in combination with Regorafenib and hepatic artery bicarbonate infusion
Arm Type
Experimental
Arm Description
Serplulimab: once every two weeks; Regorafenib: from the first day to the 21th day; hepatic artery bicarbonate infusion: once every four weeks
Intervention Type
Drug
Intervention Name(s)
Serplulimab+Regorafenib
Intervention Description
Serplulimab: once every two weeks; Regorafenib: from the first day to the 21st day
Intervention Type
Drug
Intervention Name(s)
Hepatic Artery Bicarbonate Infusion
Intervention Description
hepatic artery bicarbonate infusion: once every four weeks
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
Objective Response Rate was defined as the proportion of patients with a best objective response of complete response (CR) or partial response (PR) according to RECIST criteria (version 1.1).
Time Frame
From Baseline to disease progress, up to 18 months
Secondary Outcome Measure Information:
Title
Adverse Events and Serious Adverse Events
Description
Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0.
Time Frame
From Baseline to primary completion date, about 2 years
Title
Progression free survival
Description
Progression-free survival is defined as the time from enrollment to the first documented disease progression according to RECIST version 1.1, or to death from any cause, whichever occurred first
Time Frame
From Baseline to primary completion date, about 2 years
Title
Overal survival
Description
Time from randomization to death (from any cause)
Time Frame
From Baseline to primary completion date, about 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 or above, male or female; Patients with colorectal cancer and liver metastases who strictly conform to the clinical diagnostic criteria of "Chinese Guidelines for Diagnosis and Treatment of Colorectal Cancer (2020 Edition)" or who have been confirmed by histopathology or cytology; At least 1 measurable intrahepatic lesion; Child-Pugh liver function rating: A or good B (≤7 points) ; No local treatment including radiotherapy, surgical excision and ablation was performed before interventional therapy; No other malignant tumors; ECOG score within one week before enrollment: 0-1; Predicted survival ≥24 weeks; The major organs are functioning normally; the following criteria are met: Blood examination: a) HB≥90 g/L;b) ANC≥1.5×109/L;c) PLT≥80×109/L; Biochemical examination: a) ALB ≥29 g/L;b) ALT and AST<5ULN;c) TBIL ≤1.5ULN;d) Creatinine≤1.5ULN;(Only one of the two measures of albumin and bilirubin in the Child-Pugh rating can be a score of 2); Thyroid function tests are within normal range; Women of childbearing age must already be using reliable contraception or have had a pregnancy test (serum or urine) with negative results within 7 days prior to inclusion and be willing to use an appropriate method of contraception during the trial period and 8 weeks after the last test drug administration; The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up; Exclusion Criteria: There is a contraindication of anti-PD-1 monoclonal antibody therapy; With other uncured malignancies, except for cured basal cell carcinoma of the skin and cervical carcinoma in situ; Patients who are preparing for an organ transplant or have had an organ transplant in the past; Ascites with clinical symptoms that require therapeutic abdominal puncture or drainage, or Child-Pugh score > 2; Patients with high blood pressure (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg) who cannot be reduced to the normal range by antihypertensive medication; Patients with grade Ⅱ or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval ≥450 ms for males and 470 ms for females); A history of symptomatic ischemic or hemorrhagic cerebrovascular disease; Having multiple factors that affect oral medication (such as inability to swallow, chronic diarrhea, and intestinal obstruction, which significantly affects drug administration and absorption); Patients with a history of gastrointestinal bleeding or a definite tendency to gastrointestinal bleeding within the past 6 months, such as esophageal varicose veins with bleeding risk, locally active ulcer lesions, stool occult blood ≥ (++), should not be included in the group; If fecal occult blood (+), gastroscopy is required; Had an abdominal fistula, gastrointestinal perforation, or abdominal abscess in the 28 days prior to joining the study; Patients with abnormal coagulation function (INR > 1.5 or prothrombin time (PT) > ULN+4 seconds) who are prone to bleeding or are receiving thrombolytic or anticoagulant therapy; Patients with central nervous system metastases or known brain metastases; Patients with past and current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, and severe impairment of lung function; Urine routine showed urine protein ≥++ or confirmed 24 hours urine protein quantity > 1.0 g; Severe thyroid disease cannot be controlled by treatment; Rheumatic or autoimmune diseases, and immunosuppressant or high-dose hormone therapy after organ transplantation;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shanshan Weng
Phone
+86-13758118823
Email
2310053@zju.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Ying Yuan
Phone
+86-13858193601
Email
yuanying1999@zju.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ying Yuan
Organizational Affiliation
The Second Affiliated Hospital of Medical College of Zhejiang University
Official's Role
Study Chair
Facility Information:
Facility Name
the Second Affiliated Hospital of Medical College of Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China

12. IPD Sharing Statement

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Serplulimab+Regorafenib +Hepatic Artery Bicarbonate Infusion in Patients With Colorectal Cancer and Liver Metastases

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