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RC48-ADC Combined With Bevacizumab in HER2-positive Advanced Colorectal Cancer

Primary Purpose

Colorectal Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
RC48-ADC plus Bevacizumab
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 RC48-ADC, Her2-positive, Colorectal Cancer

Eligibility Criteria

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

Inclusion Criteria: Age 18 or above, male or female; Advanced inoperable colorectal cancer confirmed by pathology; At least 1 measurable lesion meeting RECIST v1.1 criteria; Patients who had received at least oxaliplatin, irinotecan, and fluorouracil for advanced or metastatic disease progressed or were intolerant were admitted to the study; Patients who had previously received anti-HER2 therapy such as trastuzumab and lapatinib were allowed to be included; ECOG PS: 0-2 points; Patients with HER2 expression: IHC results 2+ or 3+. Predicted survival ≥12 weeks; 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. For males, consent is required to use an appropriate method of contraception or surgical sterilization during the trial period and 8 weeks after the last administration of the trial drug; The subjects voluntarily joined the study and signed the informed consent. The subjects had good compliance and cooperated with follow-up visits. Exclusion Criteria: Known allergy to MMAE conjugate of recombinant humanized anti-HER2 monoclonal antibody for injection; Clinical symptoms or diseases of the heart that are not well controlled, such as heart failure of grade 2 or above; b. Unstable angina pectoris; c. Myocardial infarction within 1 year; d. Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; There are contraindications for the use of bevacizumab such as severe active bleeding, severe arteriovenous thrombosis events, gastrointestinal obstruction and perforation, and uncontrolled hypertension Major surgical treatment, open biopsy, or significant traumatic injury was received within 28 years prior to treatment In the investigator's judgment, subjects had other factors that might have led to the termination of the study, such as other serious medical conditions (including mental illness) requiring concomitant treatment, serious laboratory abnormalities, and family or social factors that might have affected subjects' safety or the collection of data and samples.

Sites / Locations

  • The second affiliated hospital of Zhejiang University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RC48-ADC plus Bevacizumab

Arm Description

Administer RC48-ADC intravenously in combination with bevacizumab 5mg/kg once every two weeks. Medication must be discontinued until disease progression, intolerable toxicity, informed consent is withdrawn, or investigator judgment is made.

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

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
March 13, 2023
Last Updated
March 24, 2023
Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
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1. Study Identification

Unique Protocol Identification Number
NCT05785325
Brief Title
RC48-ADC Combined With Bevacizumab in HER2-positive Advanced Colorectal Cancer
Official Title
RC48-ADC Combined With Bevacizumab in HER2-positive Advanced Colorectal Cancer:a Single-arm, Non-randomized, Single-center Trial
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2023 (Anticipated)
Primary Completion Date
December 1, 2023 (Anticipated)
Study Completion Date
December 1, 2024 (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

5. Study Description

Brief Summary
A phase II clinical study of RC48-ADC combined with Bevacizumab as late-line treatment in patients with HER2-expressed metastatic colorectal cancer. A total of 30 patients are planned to be enrolled.
Detailed Description
This is a single-arm, non-randomized, single-center trial. Enroll 30 patients with HER2-expressed metastatic colorectal cancer and failure of standard therapy. Divide into 2 cohorts, including 10 patients with low HER2 expression (IHC 2+/FISH negative) and 20 patients with high HER2 expression (IHC 2+/FISH positive or IHC3+). Administer RC48-ADC intravenously in combination with bevacizumab 5mg/kg once every two weeks. Medication must be discontinued until disease progression, intolerable toxicity, informed consent is withdrawn, or investigator judgment is made. The primary endpoints 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
Keywords
RC48-ADC, Her2-positive, Colorectal Cancer

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
RC48-ADC plus Bevacizumab
Arm Type
Experimental
Arm Description
Administer RC48-ADC intravenously in combination with bevacizumab 5mg/kg once every two weeks. Medication must be discontinued until disease progression, intolerable toxicity, informed consent is withdrawn, or investigator judgment is made.
Intervention Type
Drug
Intervention Name(s)
RC48-ADC plus Bevacizumab
Intervention Description
Administer RC48-ADC intravenously in combination with bevacizumab 5mg/kg once every two 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
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; Advanced inoperable colorectal cancer confirmed by pathology; At least 1 measurable lesion meeting RECIST v1.1 criteria; Patients who had received at least oxaliplatin, irinotecan, and fluorouracil for advanced or metastatic disease progressed or were intolerant were admitted to the study; Patients who had previously received anti-HER2 therapy such as trastuzumab and lapatinib were allowed to be included; ECOG PS: 0-2 points; Patients with HER2 expression: IHC results 2+ or 3+. Predicted survival ≥12 weeks; 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. For males, consent is required to use an appropriate method of contraception or surgical sterilization during the trial period and 8 weeks after the last administration of the trial drug; The subjects voluntarily joined the study and signed the informed consent. The subjects had good compliance and cooperated with follow-up visits. Exclusion Criteria: Known allergy to MMAE conjugate of recombinant humanized anti-HER2 monoclonal antibody for injection; Clinical symptoms or diseases of the heart that are not well controlled, such as heart failure of grade 2 or above; b. Unstable angina pectoris; c. Myocardial infarction within 1 year; d. Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; There are contraindications for the use of bevacizumab such as severe active bleeding, severe arteriovenous thrombosis events, gastrointestinal obstruction and perforation, and uncontrolled hypertension Major surgical treatment, open biopsy, or significant traumatic injury was received within 28 years prior to treatment In the investigator's judgment, subjects had other factors that might have led to the termination of the study, such as other serious medical conditions (including mental illness) requiring concomitant treatment, serious laboratory abnormalities, and family or social factors that might have affected subjects' safety or the collection of data and samples.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Caixia Dong
Phone
+86 15068882349
Email
dcx_1982@163.com
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 Zhejiang University
City
Hangzhou
State/Province
Zhejinag
ZIP/Postal Code
310009
Country
China

12. IPD Sharing Statement

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RC48-ADC Combined With Bevacizumab in HER2-positive Advanced Colorectal Cancer

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