Disitamab Vedotin + Pyrotinib Versus THP in the First-line Treatment for HER2+ Advanced Breast Cancer Clinical Trial

February 22, 2024 updated by: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Disitamab Vedotin in Combination With Pyrotinib Versus THP in the First-line Treatment for HER2-positive Advanced Breast Cancer, a Multicentre, Randomized, Double-blind Controlled, Phase III Trial

The goal of this multicentre, randomized, double-blind controlled, phase III clinical trial is to compare the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab (THP) for newly diagnosed recurrent/metastatic Human epidermal growth factor receptor 2 (HER2) positive advanced breast cancer, and to explore the impact of biomarkers on clinical efficacy and safety. The main questions it aims to answer are:

  • Analyse the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of THP.
  • Explore the impact of biomarkers on clinical efficacy and safety of the combination of disitamab vedotin in combination with pyrotinib treatment.

Participants in the experimental group will receive disitamab vedotin in combination with pyrotinib for 6-8 cycles (each cycle lasting 28 days), followed by maintenance treatment with trastuzumab in combination with pyrotinib. Participants in the control group will receive paclitaxel in combination with trastuzumab and pertuzumab for 6-8 cycles (each cycle lasting 21 days), followed by maintenance treatment with trastuzumab and pertuzumab.

Researchers will compare disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab to see if disitamab vedotin in combination with pyrotinib could be a new option for first-line treatment of HER2-positive metastatic breast cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

312

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510000
        • Recruiting
        • Sun Yat-sen Memorial Hospital，Sun Yat-sen University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adult female patients (age 18-75 years) with metastatic breast cancer confirmed by pathology or imaging;
  2. Pathologically confirmed HER2 positive (definition: Immunohistochemistry(IHC) 3+, or IHC 2+ and Fluorescent In Situ Hybridization(FISH) amplification);
  3. No previous chemotherapy regimen for metastatic breast cancer;
  4. At least one measurable lesion exists (Response Evaluation Criteria in Solid Tumors(RECIST) 1.1);
  5. Eastern Cooperative Oncology Group(ECOG) performance status score ≤ 2 and expected survival of not less than 3 months;
  6. Prior treatment-related toxicity at enrollment must have resolved to National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE) (version 5.0) ≤ 1 degree (except for alopecia or other toxicity that, in the judgment of the investigator, is not considered a risk to the safety of the patient);

  7. Patients with adequate organ function before enrollment:

    1. White Blood Cell (WBC) ≥ 3.0 x 10^9/L;
    2. Neutrophil granulocyte (ANC) ≥1.5 x 10^9/L;
    3. Platelet (PLT) ≥70×10^9/L;

  8. Liver, kidney, and cardiac function tests are essentially normal (based on the normal values in the laboratory of each study center):

    1. Total bilirubin (TBIL) ≤ 3 x Upper Limit of Normal (ULN);
    2. Alanine aminotransferase (ALT/AST) ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver metastases);
    3. serum creatinine ≤ 1.5 x ULN or creatinine clearance (Ccr) ≥ 60 ml/min;

  9. . Normal cardiac function;

    1. Left ventricular ejection fraction (LVEF) ≥ 55%;
    2. QT-interval corrected with Fridericia (QTcF) ≤ 470ms;
  10. Hormone receptor status is clear;
  11. Female patients of childbearing potential who have a negative pregnancy test and agree to use an effective non-hormonal method of contraception during treatment and for at least 6 months after the last dose of the test drug;
  12. Able to understand the study process, voluntarily participate in this study, and sign an informed consent form.

Exclusion Criteria:

  1. Pathology suggestive of HER2 negativity (IHC 2+ and FISH-, or IHC 1+);
  2. Patients with known hypersensitivity to the active ingredient or other components of the study drug;
  3. Patients during pregnancy or lactation, patients with childbearing potential tested positive in a baseline pregnancy test, or patients unwilling to take effective contraceptive measures throughout the trial;
  4. Patients not eligible for this study judged by the investigator, a pre-existing disease or condition that may interfere with participation in the study or any serious medical disorder that may interfere with the safety of the subject (e.g., uncontrolled heart disease, high blood pressure, active or uncontrolled infections, active hepatitis B virus infection).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: disitamab vedotin in combination with pyrotinib
disitamab vedotin 2mg/kg IV every 14 days + Pyrotinib 400mg PO daily, with each 28-day cycle. After 6-8 cycles, adding Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pyrotinib 400mg PO daily for maintenance.
Drug: disitamab vedotin
disitamab vedotin 2mg/kg iv q2w
Other Names:
  • RC-48
Drug: Pyrotinib
pyrotinib 400mg po q28d
Drug: trastuzumab
trastuzumab 8mg/kg for the first cycle, 6mg/kg for subsequent treatments iv q21d
Active Comparator: taxane drug in combination with trastuzumab and pertuzumab
taxane drug (Docetaxel/Paclitaxel/Albumin Paclitaxel/Liposomal Paclitaxel, dosing and administration per latest National Comprehensive Cancer Network(NCCN) and Chinese Society of Clinical Oncology(CSCO) breast cancer guidelines) + Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pertuzumab initially at 840mg IV followed by 420mg IV every 21 days, with each 21-day cycle. After 6-8 cycles, continuing with Trastuzumab at 6mg/kg IV every 21 days + Pertuzumab at 420mg IV every 21 days for maintenance.
Drug: trastuzumab
trastuzumab 8mg/kg for the first cycle, 6mg/kg for subsequent treatments iv q21d
Drug: Pertuzumab
pertuzumab 840mg for the first cycle, 420mg for subsequent treatments iv q21d
Drug: taxane drug
Docetaxel/paclitaxel/albumin paclitaxel/liposomal paclitaxel, dosage and administration are determined according to the latest version of the NCCN and CSCO breast cancer guideline recommendations

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: Estimated 30 months
From enrollment to progression or death (for any reason)
Estimated 30 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Estimated 8 years
From enrollment to death (for any reason)
Estimated 8 years
Disease control rate (DCR)
Time Frame: Estimated 30 months
Ratio of complete response (CR) , partial response (PR) and stable disease (SD) in all subjects
Estimated 30 months
Objective Response Rate (ORR)
Time Frame: Estimated 30 months
Ratio of CR and PR in all subjects
Estimated 30 months
Clinical Benefit rate (CBR)
Time Frame: Estimated 30 months
Ratio of CR,PR and SD greater than or equal to 24 weeks in all subjects
Estimated 30 months
Adverse Events (Based on CTCAE 5.0 standards)
Time Frame: From informed consent through 28 days following treatment completion
Safety
From informed consent through 28 days following treatment completion
Quality of Life (QoL) by Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B)
Time Frame: Estimated 30 months
QoL was assessed using FACT-B. FACT-B is a 37-item questionnaire with 5 subscales assessing physical, social, emotional, and functional well-being, with scores ranging from 0 to 4 for each question. Higher scores generally indicating a better quality of life.
Estimated 30 months
Exploration of biomarkers
Time Frame: Estimated 30 months
Next Generation Gene Sequencing (NGS) detection of tissue and blood specimens, including ERBB1/ERBB2/ERBB3/ERBB4/AKT/TP53/PIK3CA and so on. Objective to explore the correlation between biomarkers and the objective response rate (ORR), as well as progression-free survival (PFS).
Estimated 30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 6, 2023

Primary Completion (Estimated)

June 30, 2031

Study Completion (Estimated)

June 30, 2031

Study Registration Dates

First Submitted

August 7, 2023

First Submitted That Met QC Criteria

February 22, 2024

First Posted (Actual)

February 26, 2024

Study Record Updates

Last Update Posted (Actual)

February 26, 2024

Last Update Submitted That Met QC Criteria

February 22, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SYSKY-2023-431-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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