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

Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT04760431
Collaborator
Peking University International Hospital (Other), Sun Yat-sen University (Other), Zhejiang University (Other)
120
Enrollment
3
Locations
2
Arms
48
Anticipated Duration (Months)
40
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

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
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).

Study Design

Study Type:
Interventional
Anticipated 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
Anticipated Study Start Date :
Oct 1, 2021
Anticipated Primary Completion Date :
Sep 30, 2024
Anticipated Study Completion Date :
Sep 30, 2025

Arms and Interventions

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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Pyrotinib, Neratinib, Tucatinib

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate (ORR) [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) [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) [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: 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 Appearance of 1 or more new lesions Unequivocal progression of existing non-target lesions

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

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

    6. Peripheral neurotoxicity [30 days after last treatment]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    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:

    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Peking University International Hospital Beijing Beijing China 102206
    2 Sun Yat-sen University Cancer Center Guangzhou Guangdong China 510000
    3 First Affiliated Hospital, Zhejiang University, School of Medicine Hangzhou Zhejiang China 310000

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Xuexin He, MD, Second Affiliated Hospital, Zhejiang University, School of Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Second Affiliated Hospital, School of Medicine, Zhejiang University
    ClinicalTrials.gov Identifier:
    NCT04760431
    Other Study ID Numbers:
    • HER2BRAIN
    First Posted:
    Feb 18, 2021
    Last Update Posted:
    Jun 2, 2021
    Last Verified:
    Jan 1, 2021
    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:
    Breast Neoplasms
    Neoplasm Metastasis
    Neoplasms, Second Primary
    Brain Neoplasms
    Paclitaxel
    Docetaxel
    Albumin-Bound Paclitaxel
    Trastuzumab
    Pertuzumab
    Taxane
    Tucatinib

    Study Results

    No Results Posted as of Jun 2, 2021