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

NCT ID: NCT04760431

Last Updated: 2021-06-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-01
• Study Completion Date: 2025-09-30

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).

Conditions

HER2-positive Breast Cancer; Brain Metastases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group A

Trastuzumab, Taxanes and Pertuzumab

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: 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.

Taxanes

Intervention Type: 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

Pertuzumab

Intervention Type: 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.

Group B

Trastuzumab, Taxanes and TKIs

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: 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.

Taxanes

Intervention Type: 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

Tyrosine kinase inhibitor

Intervention Type: 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

Interventions

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.

Intervention Type: 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

Intervention Type: 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.

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Herceptin; Docetaxel, Paclitaxel, Paclitaxel (Albumin bound), Paclitaxel Liposome; Perjeta; Pyrotinib, Neratinib, Tucatinib

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Peking University International Hospital

OTHER

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: collaborator

Zhejiang University

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xuexin He, MD

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital, Zhejiang University, School of Medicine

Locations

Peking University International Hospital

Beijing, Beijing Municipality, China

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

First Affiliated Hospital, Zhejiang University, School of Medicine

Hangzhou, Zhejiang, China

Countries

China

Central Contacts

Xuexin He, MD

Role: CONTACT

xuexinhe@zju.edu.cn

18329139569 ext. 86

Facility Contacts

Haiyan Wei, MD

Role: primary

Other Identifiers

HER2BRAIN

Identifier Type: -

Identifier Source: org_study_id