Pyrotinib Rechallenge in Her2-positive Metastatic Breast Cancer Pretreated With Pyrotinib and Trastuzumab

Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This study is a randomized, open-label, multi-center, parallel design study of the combination of pyrotinib, trastuzumab and chemotherapy versus trastuzumab and chemotherapy in HER2+ MBC patients, who have prior received trastuzumab and pyrotinib. Patients will be randomized in a 2:1 ratio to one of the following treatment arms. Arm A: pyrotinib + trastuzumab + chemotherapy, Arm B: trastuzumab + chemotherapy. Patients will receive either arm of therapy until disease progression, unacceptable toxicity, or withdrawal of consent.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer; HER2-positive Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab plus chemotherapy; Drug: Trastuzumab in combination with pyrotinib plus chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged ≥18 and ≤75 years;
2. Pathologically confirmed HER2 positive patients with recurrence/ metastatic breast cancer: HER2 IHC 3+, or HER2 IHC 2+ and FISH detection gene amplification;
3. History of trastuzumab-containing chemotherapy in neoadjuvant, adjuvant or recurrence/ metastatic setting;
4. History of pyrotinib-containing chemotherapy in neoadjuvant or recurrence/ metastatic setting;
5. Previously reveived ≤2 systemic treatment in recurrence/ metastasis setting; (anti-HER2 ADCs such as T-DM1 is included in chemotherapy regimens, endocrine therapy alone is not included);
6. ECOG performance status of 0 to 1;
7. According to RECIST 1.1, at least one extracranial measurable lesion exists；
8. Signed informed consent.

Exclusion Criteria:

1. Patients with leptomeningeal metastasis or unstable brain metastasis;
2. History of neurological or psychiatric disorders;
3. Second malignancies within 5 years, except for cured skin basal cell carcinoma, carcinoma in-situ of uterine cervix and squamous-cell carcinoma;
4. Undergone major surgical procedures or significant trauma within 4 weeks prior to randomization, or expected to undergo major surgery.
5. Factors influencing the usage of oral administration (e.g. unable to swallow, chronic diarrhea and intestinal obstruction, etc.);
6. History of allergies to the drug components of this regimen;
7. History of Immunodeficiency, acquired or congenital immunodeficiency (HIV positive), history of organ transplantation;
8. Any other situations judged by investigator as not suitable for participating in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Trastuzumab plus chemotherapy	Drug: Trastuzumab plus chemotherapy; Trastuzumab: 8 mg/kg loading dose followed by 6 mg/kg, Q3W Chemotherapy regimen is chosen from the following: Vinorelbine, Gemcitabine, taxanes or Eribulin monotherapy Experimental: Pyrotinib +Trastuzumab + chemotherapy
EXPERIMENTAL: Pyrotinib in combination with Trastuzumab plus chemotherapy	Drug: Trastuzumab in combination with pyrotinib plus chemotherapy; Pyrotinib: 400 mg po QD, Q3W Chemotherapy regimen is chosen from the following: Vinorelbine, Gemcitabine, taxanes or Eribulin monotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival (PFS)	approximately 8 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	approximately 8 months
Adverse Events (AEs)	From the first drug administration to within 28 days for the last treatment

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 15, 2021
• Primary Completion (ANTICIPATED): October 31, 2023
• Study Completion (ANTICIPATED): October 31, 2024

Study Registration Dates

• First Submitted: April 20, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (ACTUAL): April 26, 2022

Study Record Updates

• Last Update Posted (ACTUAL): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 20, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: YBCSG-21-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No