Clinical trial NCT04760431: TKIs vs. Pertuzumab in HER2+ Breast Cancer Patients With Active Brain Metastases (HER2BRAIN)
Official title: Anti-HER2 TKI Versus Pertuzumab in Combination With Dose-dense Trastuzumab and Taxane as First Line in HER2-positive Breast Cancer Patients With Active Brain Metastases: A Phase II, Multicenter, Double-blind, Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: HER2-positive Breast Cancer
Brain Metastases
Keywords: HER2-positive Breast Cancer
Brain Metastases
Tyrosine kinase inhibitors
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: Peking University International Hospital
name: Sun Yat-sen University
name: Zhejiang University
First posted: 2021-02-18
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective, randomized, 2-arm, Phrase 2, superiority and multicenter study to compare the efficiency of Anti-HER2 TKI versus Pertuzumab in Combination With Dose-dense Trastuzumab and Taxane in HER2-positive breast cancer patients with active refractory brain metastases.

Detailed description: This is a prospective, randomized, 2-arm, Phrase 2, superiority and multicenter study. HER2-positive breast cancer patients with active refractory brain metastases are included. There will be two group: Group A (Trastuzumab, Taxanes and Pertuzumab) and Group B (Trastuzumab, Taxanes and TKIs). The primary outcome is objective response rate (ORR).

Eligibility criteria: Inclusion Criteria:

1. Patients provided written informed consent
2. Women aged 18-75 years
3. Histologically or cytologically confirmed HER2-positive (IHC 3+ or ISH+) breast cancer
4. Patients of HER2 positive breast cancer with a documented central nervous system (CNS) recurrence/progression (by imaging) during or after Trastuzumab based therapy
5. At least one measurable and progressive lesion in the CNS (≥10 mm on T1-weighted, gadolinium-enhanced MRI)
6. Previous treatment with HER2 inhibitors to be discontinued prior to first study treatment administration (at least 14 days for trastuzumab and other antibodies, at least 7 days for lapatinib)
7. Previous chemotherapy and hormonal therapy (adjuvant and metastatic regimens) allowed, but chemotherapy must have been discontinued at least 14 days and hormonal therapy at least 7 days prior to first study treatment administration
8. Prior surgery, whole brain radiotherapy or stereotactic radiosurgery allowed provided that there is unequivocal evidence of one or more new and/or progressive brain metastases after completion of whole brain radiotherapy or stereotactic radiosurgery
9. Previous radiotherapy allowed, but radiotherapy must have been discontinued at least 14 days prior to first study treatment administration
10. Normal cardiac function
11. Patients must have recovered to baseline condition or to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade = 1 from any acute CTCAE v. 5.0 grade =2 side effects of previous treatments
12. Without infection of human immunodeficiency virus (HIV) on central laboratory assay results prior to randomization
13. Alanine aminotransferase (ALT) \</= 2.5 × the upper limit of normal (ULN), Aspartate aminotransferase (AST) \</= 2.5 × ULN prior to randomization
14. Total bilirubin (TBIL) \</= 1.25 × ULN
15. Alkaline phosphatase (ALK) \</= 2.5 × ULN
16. Gamma glutamyl transpeptidase (GGT) \</= 2.5 × ULN
17. Albumin \>/= 30g/L
18. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1
19. A life expectancy of at least 1 month
20. Women of child-bearing age should take effective contraceptive measures
21. Serum total bilirubin (TBil) \</= 1.5 × ULN
22. Serum creatinine (Scr) \</= 1.5 × ULN
23. WBC \>/= 3×109/L, Blood neutrophil count \>/= 1×109/L, Platelet count \>/= 100×109/L, HB \>/= 9 g/dL

Exclusion Criteria:

1. Lack of histological or cytological confirmation of HER2-positive (IHC 3+ or ISH-positive) breast cancer
2. Cerebral hernia
3. Need radiotherapy or surgery immediately
4. Active cerebral infarction or hemorrhage
5. Only meningeal metastasis
6. Earlier exposure to doxorubicin or pirarubicin at a dosage of more than 360 mg/m2
7. Earlier exposure to epirubicin at a dosage of more than 900 mg/m2
8. Prior treatment with HER2-tyrosine kinase inhibitors
9. Treatment with trastuzumab emtansine within 6 months
10. Any other current malignancy or malignancy diagnosed within the past five years (other than carcinoma in situ or stage Ia carcinoma of the cervix, skin basal cell carcinoma and papillary thyroid carcinoma at early stage)
11. Active infection with human immunodeficiency virus (HIV) prior to first study treatment administration.
12. History of participating any other clinical trials within 30 days prior to randomization
13. Known hypersensitivity (Grade 3 or 4) to any of the trial drugs
14. Pregnancy or lactation
15. Current severe systemic disease (for example, clinically significant cardiovascular, pulmonary, or renal disease)
16. Legal incompetence or limitation.
17. Considered unable to complete the study or sign the informed consent due to a medical or mental disorder by the investigator.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: up to 3 years
Secondary outcomes:
measure: Objective Response Rate 2 (ORR2)
timeFrame: up to 3 years
measure: Progression-free Survival (PFS)
timeFrame: up to 3 years
measure: Overall Survival (OS)
timeFrame: up to 3 years
measure: Clinical benefit rate (CBR)
timeFrame: up to 3 years
measure: Disease control rate (DCR)
timeFrame: up to 3 years
measure: Peripheral neurotoxicity
timeFrame: 30 days after last treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University International Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Hangzhou
country: China
facility: First Affiliated Hospital, Zhejiang University, School of Medicine
state: Zhejiang
Study officials:
affiliation: Second Affiliated Hospital, Zhejiang University, School of Medicine
name: Xuexin He, MD
role: PRINCIPAL_INVESTIGATOR
References: