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Not yet recruitingNCT04760431Updated Jun 2, 2021

TKIs vs. Pertuzumab in HER2+ Breast Cancer Patients With Active Brain Metastases (HER2BRAIN)

A Phase 2 interventional study of Trastuzumab and Taxanes in HER2-positive Breast Cancer and Brain Metastases, sponsored by Second Affiliated Hospital, School of Medicine, Zhejiang University. Not yet recruiting at 3 sites in China. Open to female participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-06-02.

Sponsored by Second Affiliated Hospital, School of Medicine, Zhejiang University · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Primary completion was expected by Sep 2024, 2 years ago, but the record still lists the study as not yet recruiting.
Phase
Phase 2
Study type
Interventional
Enrollment
120
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
Female
01

Study 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.

Read the 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).

02

Conditions studied

  • HER2-positive Breast Cancer
  • Brain Metastases

Keywords

  • HER2-positive Breast Cancer
  • Brain Metastases
  • Tyrosine kinase inhibitors
03

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's planned enrollment of 120 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University is the lead sponsor of 1,058 studies on the registry; 511 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
Female
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
120 participants (estimated)

Study arms

  • Active comparator
    Group A

    Trastuzumab, Taxanes and Pertuzumab

    Drug: Trastuzumab · Drug: Taxanes · Drug: Pertuzumab

  • Experimental
    Group B

    Trastuzumab, Taxanes and TKIs

    Drug: Trastuzumab · Drug: Taxanes · Drug: Tyrosine kinase inhibitor

Interventions

  • DrugTrastuzumab

    8 mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles, administered by IV infusion every week until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

    Also known as: Herceptin

  • DrugTaxanes

    Docetaxel: 75 mg/m2, administered by IV infusion every 3 weeks Paclitaxel: 175 mg/m2, administered by IV infusion every 3 weeks Paclitaxel (Albumin bound): 260 mg/m2, administered by IV infusion every 3 weeks Paclitaxel Liposome: 135-175 mg/m2, administered by IV infusion every 3 weeks

    Also known as: Docetaxel, Paclitaxel, Paclitaxel (Albumin bound), Paclitaxel Liposome

  • DrugPertuzumab

    840 milligrams (mg) loading dose of pertuzumab, followed every 3 weeks thereafter by a dose of 420 mg via intravenous (IV) infusion until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

    Also known as: Perjeta

  • DrugTyrosine kinase inhibitor

    Pyrotinib: 400mg po within 30 minutes after a meal, QD, every 3 weeks Neratinib: 240mg po QD, every 3 weeks Tucatinib: 300mg po Q12H

    Also known as: Pyrotinib, Neratinib, Tucatinib

06

What researchers measure

Primary outcomes

  1. Objective Response Rate (ORR)

    The sum of complete response (CR) rate and partial response (PR) rate by measurement of target lesions (intracranial lesions)

    Time frame: up to 3 years

Secondary outcomes

  1. Objective Response Rate 2 (ORR2)

    The sum of complete response (CR) rate and partial response (PR) rate by measurement of extracranial lesions

    Time frame: up to 3 years

  2. Progression-free Survival (PFS)

    PFS is defined as time from randomization to disease progression or death, whichever occurs first. Progression of disease was determined if at least 1 of the following criteria applied: 1. At least a 20% increase in the sum of the diameters (SoD) of target lesions taking as reference the smallest SoD recorded since the treatment started, together with an absolute increase in the SoD of at least 5 mm 2. Appearance of 1 or more new lesions 3. Unequivocal progression of existing non-target lesions

    Time frame: up to 3 years

  3. Overall Survival (OS)

    OS is defined as time from randomization to death for any cause. If there is no death reported for a subject before the date cutoff for OS analysis, OS will be censored at the last contact date at which the subject is known to be alive. For patients who had not died up to the cut-off date, the date they were last known to be alive was derived from the patient status records, the trial completion record, radiological imaging assessments, the study treatment termination record, and the randomization date.

    Time frame: up to 3 years

  4. Clinical benefit rate (CBR)

    CBR is defined as the sum of CR rate, PR rate, and more than 6 months' SD (stable disease) rate

    Time frame: up to 3 years

  5. Disease control rate (DCR)

    DCR is defined that the sum of CR rate, PR rate, and SD rate.

    Time frame: up to 3 years

  6. Peripheral neurotoxicity

    Peripheral neurotoxicities are defined as the number of patients who suffer from neurotoxicities (NCI CTCAE v5.0)

    Time frame: 30 days after last treatment

07

Study locations

3 sites
  • Peking University International Hospital
    Beijing, Beijing 102206, China
  • Sun Yat-sen University Cancer Center
    Guangzhou, Guangdong 510000, China
  • First Affiliated Hospital, Zhejiang University, School of Medicine
    Hangzhou, Zhejiang 310000, China
    • Haiyan Wei, MD · Contact
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 2, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT04760431
Lead sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborators
Peking University International Hospital, Sun Yat-sen University, Zhejiang University
Responsible party
Sponsor
First posted
Feb 18, 2021
Start date
Oct 1, 2021 (estimated)
Primary completion
Sep 30, 2024 (estimated)
Completion
Sep 30, 2025 (estimated)
Last update
Jun 2, 2021

Study contacts

Xuexin He, MD
Contact
xuexinhe@zju.edu.cn
18329139569 ext. 86
Xuexin He, MD
principal investigator · Second Affiliated Hospital, Zhejiang University, School of Medicine

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is not yet recruiting, as verified in Jan 2021. You cannot join it, but the record below documents what was studied.

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