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

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ClinicalTrials.gov Identifier: NCT04760431
Recruitment Status : Not yet recruiting
First Posted : February 18, 2021
Last Update Posted : June 2, 2021
Sponsor:
Collaborators:
Peking University International Hospital
Sun Yat-sen University
Zhejiang University
Information provided by (Responsible Party):
Second Affiliated Hospital, School of Medicine, Zhejiang University

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.

Condition or disease Intervention/treatment Phase
HER2-positive Breast Cancer Brain Metastases Drug: Trastuzumab Drug: Taxanes Drug: Pertuzumab Drug: Tyrosine kinase inhibitor Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Estimated Study Start Date : October 1, 2021
Estimated Primary Completion Date : September 30, 2024
Estimated Study Completion Date : September 30, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Active Comparator: Group A
Trastuzumab, Taxanes and Pertuzumab
Drug: Trastuzumab
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.
Other Name: Herceptin

Drug: Taxanes
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
Other Name: Docetaxel, Paclitaxel, Paclitaxel (Albumin bound), Paclitaxel Liposome

Drug: Pertuzumab
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.
Other Name: Perjeta

Experimental: Group B
Trastuzumab, Taxanes and TKIs
Drug: Trastuzumab
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.
Other Name: Herceptin

Drug: Taxanes
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
Other Name: Docetaxel, Paclitaxel, Paclitaxel (Albumin bound), Paclitaxel Liposome

Drug: Tyrosine 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
Other Name: Pyrotinib, Neratinib, Tucatinib




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: up to 3 years ]
    The sum of complete response (CR) rate and partial response (PR) rate by measurement of target lesions (intracranial lesions)


Secondary Outcome Measures :
  1. Objective Response Rate 2 (ORR2) [ Time Frame: up to 3 years ]
    The sum of complete response (CR) rate and partial response (PR) rate by measurement of extracranial lesions

  2. Progression-free Survival (PFS) [ Time Frame: up to 3 years ]

    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

  3. Overall Survival (OS) [ Time Frame: up to 3 years ]

    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.


  4. Clinical benefit rate (CBR) [ Time Frame: up to 3 years ]
    CBR is defined as the sum of CR rate, PR rate, and more than 6 months' SD (stable disease) rate

  5. Disease control rate (DCR) [ Time Frame: up to 3 years ]
    DCR is defined that the sum of CR rate, PR rate, and SD rate.

  6. Peripheral neurotoxicity [ Time Frame: 30 days after last treatment ]
    Peripheral neurotoxicities are defined as the number of patients who suffer from neurotoxicities (NCI CTCAE v5.0)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04760431


Contacts
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Contact: Xuexin He, MD 18329139569 ext 86 xuexinhe@zju.edu.cn

Locations
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China, Beijing
Peking University International Hospital
Beijing, Beijing, China, 102206
China, Guangdong
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China, 510000
China, Zhejiang
First Affiliated Hospital, Zhejiang University, School of Medicine
Hangzhou, Zhejiang, China, 310000
Contact: Haiyan Wei, MD         
Sponsors and Collaborators
Second Affiliated Hospital, School of Medicine, Zhejiang University
Peking University International Hospital
Sun Yat-sen University
Zhejiang University
Investigators
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Principal Investigator: Xuexin He, MD Second Affiliated Hospital, Zhejiang University, School of Medicine
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Responsible Party: Second Affiliated Hospital, School of Medicine, Zhejiang University
ClinicalTrials.gov Identifier: NCT04760431    
Other Study ID Numbers: HER2BRAIN
First Posted: February 18, 2021    Key Record Dates
Last Update Posted: June 2, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Second Affiliated Hospital, School of Medicine, Zhejiang University:
HER2-positive Breast Cancer
Brain Metastases
Tyrosine kinase inhibitors
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Paclitaxel
Docetaxel
Albumin-Bound Paclitaxel
Trastuzumab
Pertuzumab
Taxane
Tucatinib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Protein Kinase Inhibitors