Clinical trial NCT04639271: Pyrotinib, Trastuzumab And Abraxane in HER2-positive MBC With Brain Metastasis
Official title: A Single-arm, Open-label Study Of Pyrotinib Combined WithTrastuzumab And Abraxane in Patients With Brain Metastases From HER2-positive Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
HER2-positive Breast Cancer
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
First posted: 2020-11-20
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR) of Intracranial Lesion
timeFrame: Estimated up to 1 year
measure: Progression Free Survival(PFS) of Intracranial Lesion
timeFrame: Estimated up to 1 year
Secondary outcomes:
measure: Progression Free Survival(PFS)
timeFrame: Estimated up to 1 year
measure: Objective Response Rate (ORR)
timeFrame: Estimated up to 1 year
measure: disease control rate(DCR)
timeFrame: Estimated up to 1 year
Other outcomes:
Locations:
city: Jinan
country: China
facility: Zhiyong Yu
state: Shandong
Study officials:
References: