Pyrotinib, Trastuzumab And Abraxane in HER2-positive MBC With Brain Metastasis

A Single-arm, Open-label Study Of Pyrotinib Combined WithTrastuzumab And Abraxane in Patients With Brain Metastases From HER2-positive Metastatic Breast Cancer

The purpose of this study is to assess the efficacy and safety of pyrotinib combined with trastuzumab and abraxane in HER2-positive MBC with brain metastasis.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer; HER2-positive Breast Cancer
• Intervention / Treatment: Drug: Pyrotinib Plus And; Drug: Trastuzumab; Drug: Abraxane

Detailed Description

Overexpression of HER2 is associated with increased incidence of brain metastases in breast cancer, accounting for about 20-50% of HER2 positive breast cancer. Treatment strategy ranged from local therapies to systemic anti-HER2 therapies, prognosis of patients with brain metastases remains poor. Previous clinical trials had demonstrated the efficacy of trastuzumab and TKIs for brain metastasis.

Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. We designed the study to explore the efficacy and safety of pyrotinib combined with trastuzumab and abraxane in HER2-positive MBC with brain metastasis.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China
      • Zhiyong Yu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Aged >18 years.
• ECOG performance status ≤2.
• Histologically or cytologic confirmed HER2 positive advanced breast cancer.
• MRI confirmed brain metastases. According to RECIST 1.1, at least one measurable lesion exists.
• No limit of previous chemotherapy lines.
• Previously have not reveived capecitabine or disease progression of capecitabine after 6 months, or progression of capecitabine adjuvant therapy after one year;
• Life expectancy of more than 3 months.
• Required laboratory values including following parameters: ANC: ≥ 1.5 x 10^9/L;Platelet count: ≥ 100 x 10^9/L;Hemoglobin: ≥ 9.0 g/dL;Total bilirubin: ≤ 1.5 x upper limit of normal (ULN);ALT and AST: ≤ 1.5 x ULN (or ≤ 5×ULN in patients with liver metastases);BUN and creatine clearance rate: ≥ 50 mL/min;LVEF: ≥ 50%;QTcF: < 470 ms for female and < 450 ms for male.
• Signed the informed consent form prior to patient entry.

Exclusion Criteria:

• Patients with brain metastases who have extensive meningeal metastases and are treated with hormone dehydration.
• Subjects with third space fluid(such as a large amount of pleural effusion and ascites) that can not be controled by drainage or other methods. (such as pleural effusion and ascites).
• Received whole brain radiotherapy, chemotherapy, surgery or target therapy within 2 weeks prior to randomization. Received hormone therapy within 1 weeks prior to randomization, Received the nitrosoureas or mitomycin chemotherapy within 6 weeks prior to randomization.
• Participated in other clinical trial within 4 weeks prior to randomization.
• Treated or treating with HER2 tyrosine kinase inhibitors (TKIs) (including Lapatinib, Neratinib and Pyrotinib).
• Second malignancies within 5 years, except for cured carcinoma in-situ of uterine cervix, skin basal cell carcinomaand squamous-cell carcinoma.
• Receiving any other anti-tumor therapies at time of study screening visit.
• There are no other serious and/or uncontrolled diseases that may affect research participation, including any of the following: (1) unable to swallow, chronic diarrhea and intestinal obstruction and factors influencing the usage of oral administration; (2) has allergies or a known history of hypersensitivity to the drug components of this program; History of Immunodeficiency, acquired or congenital immunodeficiency (HIV positive) ,history of organ transplantation; (3) History of any kind of Heart disease, including 1) Myocardial infarction; 2) Heart failure; 3) Any other heart disease judged by researcher as not suitable for participating in this study, etc; (4) Infection.
• All female patients in breastfeeding period or in child-bearing period or with positive pregnancy test result or refusing to take a reliable method of birth control during the study.
• 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pyrotinib Plus Trastuzumab And Abraxane	Drug: Pyrotinib Plus And; Pyrotinib::400mg/d,qd,po; Drug: Trastuzumab; 8 mg/kg intravenously (IV) on Day 1 of Cycle 1, followed by 6 mg/kg on Day1 of each 21-day cycle; Drug: Abraxane; Abraxane 125mg/M2, qw iv

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) of Intracranial Lesion	Refers to the proportion of patients whose Intracranial Lesion have shrunk to a certain proportion and maintained for a certain period of time, including cases of CR and PR, RECIST 1.1 were used to assess objective tumor remission	Estimated up to 1 year
Progression Free Survival(PFS) of Intracranial Lesion	the date from the first dose to the first occurrence of Intracranial Lesion progression or death from any cause, whichever occurs first	Estimated up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival(PFS)	the date from the first dose to the first occurrence of disease progression or death from any cause, whichever occurs first	Estimated up to 1 year
Objective Response Rate (ORR)	Refers to the proportion of patients whose lesion have shrunk to a certain proportion and maintained for a certain period of time, including cases of CR and PR, RECIST 1.1 were used to assess objective tumor remission	Estimated up to 1 year
disease control rate(DCR)	Percentage of confirmed complete remission (CR), partial remission (PR), and disease stable (SD) cases in patients with evaluable efficacy	Estimated up to 1 year

Collaborators and Investigators

• Sponsor: Shandong Cancer Hospital and Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2021
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: November 19, 2020
• First Posted (Actual): November 20, 2020

Study Record Updates

• Last Update Posted (Actual): November 20, 2020
• Last Update Submitted That Met QC Criteria: November 19, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Brain Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab; Albumin-Bound Paclitaxel
• Other Study ID Numbers: ShandongCHI-16

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