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

NCT04760431 | Unknown Phase 2

• 1 other identifier: HER2BRAIN
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 3

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.

Conditions

HER2-positive Breast Cancer; Brain Metastases

Keywords

HER2-positive Breast Cancer; Brain Metastases; Tyrosine kinase inhibitors

Outcome Measures

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)

  up to 3 years

Secondary Outcomes (6)

• Objective Response Rate 2 (ORR2)

  up to 3 years

• Progression-free Survival (PFS)

  up to 3 years

• Overall Survival (OS)

  up to 3 years

• Clinical benefit rate (CBR)

  up to 3 years

• Disease control rate (DCR)

  up to 3 years

Study Arms (2)

Group A

ACTIVE COMPARATOR

Trastuzumab, Taxanes and Pertuzumab

Drug: Trastuzumab; Drug: Taxanes; Drug: Pertuzumab

Group B

EXPERIMENTAL

Trastuzumab, Taxanes and TKIs

Drug: Trastuzumab; Drug: Taxanes; Drug: Tyrosine kinase inhibitor

Interventions

Trastuzumab DRUG

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

Group A; Group B

Taxanes DRUG

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

Group A; Group B

Pertuzumab DRUG

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

Group A

Tyrosine kinase inhibitor DRUG

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

Group B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients provided written informed consent
• Women aged 18-75 years
• Histologically or cytologically confirmed HER2-positive (IHC 3+ or ISH+) breast cancer
• Patients of HER2 positive breast cancer with a documented central nervous system (CNS) recurrence/progression (by imaging) during or after Trastuzumab based therapy
• At least one measurable and progressive lesion in the CNS (≥10 mm on T1-weighted, gadolinium-enhanced MRI)
• 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)
• 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
• 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
• Previous radiotherapy allowed, but radiotherapy must have been discontinued at least 14 days prior to first study treatment administration
• Normal cardiac function
• 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
• Without infection of human immunodeficiency virus (HIV) on central laboratory assay results prior to randomization
• Alanine aminotransferase (ALT) \</= 2.5 × the upper limit of normal (ULN), Aspartate aminotransferase (AST) \</= 2.5 × ULN prior to randomization
• Total bilirubin (TBIL) \</= 1.25 × ULN
• Alkaline phosphatase (ALK) \</= 2.5 × ULN

You may not qualify if:

• Lack of histological or cytological confirmation of HER2-positive (IHC 3+ or ISH-positive) breast cancer
• Cerebral hernia
• Need radiotherapy or surgery immediately
• Active cerebral infarction or hemorrhage
• Only meningeal metastasis
• Earlier exposure to doxorubicin or pirarubicin at a dosage of more than 360 mg/m2
• Earlier exposure to epirubicin at a dosage of more than 900 mg/m2
• Prior treatment with HER2-tyrosine kinase inhibitors
• Treatment with trastuzumab emtansine within 6 months
• 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)
• Active infection with human immunodeficiency virus (HIV) prior to first study treatment administration.
• History of participating any other clinical trials within 30 days prior to randomization
• Known hypersensitivity (Grade 3 or 4) to any of the trial drugs
• Pregnancy or lactation
• Current severe systemic disease (for example, clinically significant cardiovascular, pulmonary, or renal disease)

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• Peking University International Hospital: collaborator
• Sun Yat-sen University: collaborator
• Zhejiang University: collaborator

Study Sites (3)

Peking University International Hospital

Beijing, Beijing Municipality, 102206, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510000, China

Location

First Affiliated Hospital, Zhejiang University, School of Medicine

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Trastuzumab; Taxoids; Docetaxel; Paclitaxel; pertuzumab; Tyrosine Kinase Inhibitors; pyrotinib; neratinib; tucatinib

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Xuexin He, MD

  Second Affiliated Hospital, Zhejiang University, School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xuexin He, MD

CONTACT

18329139569; xuexinhe@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: February 18, 2021
• Study Start: October 1, 2021
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2025
• Last Updated: June 2, 2021

Record last verified: 2021-01

Locations

CN (3)