HER2-positive Breast CancerPhase 2NCT04760431
TKIs vs. Pertuzumab in HER2+ Breast Cancer Patients With Active Brain Metastases (HER2BRAIN)
A Phase 2 study testing Trastuzumab, Taxanes and Pertuzumab in people with HER2-positive Breast Cancer and Brain Metastases, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 3 sites in China.
Trial 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 more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- HER2-positive Breast Cancer, Brain Metastases
- What is being tested?
- Trastuzumab, Taxanes and Pertuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 3 sitesChina
- Study dates
- 1 Oct 2021to 30 Sep 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
- Gamma glutamyl transpeptidase (GGT) </= 2.5 × ULN
- Albumin >/= 30g/L
- Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1
- A life expectancy of at least 1 month
- Women of child-bearing age should take effective contraceptive measures
- Serum total bilirubin (TBil) </= 1.5 × ULN
- Serum creatinine (Scr) </= 1.5 × ULN
- WBC >/= 3×109/L, Blood neutrophil count >/= 1×109/L, Platelet count >/= 100×109/L, HB >/= 9 g/dL
Who cannot join
- 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
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- 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)
- Legal incompetence or limitation.
- Considered unable to complete the study or sign the informed consent due to a medical or mental disorder by the investigator.
Trial locations and contacts
3 sites in 1 country.
China3 sites
Peking University International Hospital
Beijing, Beijing Municipality, 102206
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510000
First Affiliated Hospital, Zhejiang University, School of Medicine
Hangzhou, Zhejiang, 310000
Haiyan Wei, MD
About this study
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
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).
- Conditions
- HER2-positive Breast Cancer, Brain Metastases
- Being tested
- Trastuzumab, Taxanes, Pertuzumab, Tyrosine kinase inhibitor
- Keywords
- HER2-positive Breast Cancer, Brain Metastases, Tyrosine kinase inhibitors
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
Also called Herceptin
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.
TaxanesDrug
Also called Docetaxel, Paclitaxel, Paclitaxel (Albumin bound), Paclitaxel Liposome
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
PertuzumabDrug
Also called Perjeta
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.
Tyrosine kinase inhibitorDrug
Also called Pyrotinib, Neratinib, Tucatinib
Pyrotinib: 400mg po within 30 minutes after a meal, QD, every 3 weeks Neratinib: 240mg po QD, every 3 weeks Tucatinib: 300mg po Q12H
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | Trastuzumab, Taxanes and Pertuzumab Receives: Drug: Trastuzumab; Drug: Taxanes; Drug: Pertuzumab |
| Group B | Experimental | Trastuzumab, Taxanes and TKIs Receives: Drug: Trastuzumab; Drug: Taxanes; Drug: Tyrosine kinase inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
The sum of complete response (CR) rate and partial response (PR) rate by measurement of target lesions (intracranial lesions)
Measured: up to 3 years
Secondary outcomes (6)
Objective Response Rate 2 (ORR2)
The sum of complete response (CR) rate and partial response (PR) rate by measurement of extracranial lesions
Measured: up to 3 years
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:
- 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
Measured: up to 3 years
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.
Measured: up to 3 years
Clinical benefit rate (CBR)
CBR is defined as the sum of CR rate, PR rate, and more than 6 months' SD (stable disease) rate
Measured: up to 3 years
Disease control rate (DCR)
DCR is defined that the sum of CR rate, PR rate, and SD rate.
Measured: up to 3 years
Peripheral neurotoxicity
Peripheral neurotoxicities are defined as the number of patients who suffer from neurotoxicities (NCI CTCAE v5.0)
Measured: 30 days after last treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2021
- Study start1 Oct 2021 (estimated)
- Primary completion30 Sep 2024 (estimated)
- Study completion30 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-positive Breast CancerStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Peking University International Hospital, Sun Yat-sen University, Zhejiang University
- Responsible party
- Sponsor
- Investigators
- Xuexin He, MD, Principal investigator, Second Affiliated Hospital, Zhejiang University, School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04760431
- Sponsor's protocol ID
- HER2BRAIN
- Status last verified
- Jan 2021
- First submitted
- 25 Jan 2021
- Last updated
- 2 Jun 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04760431
- Acronym / sponsor ID
- HER2BRAIN
- Conditions
- HER2-positive Breast Cancer, Brain Metastases
- Keywords
- HER2-positive Breast Cancer, Brain Metastases, Tyrosine kinase inhibitors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Collaborators
- Peking University International Hospital, Sun Yat-sen University, Zhejiang University
- Study start
- 1 Oct 2021 (estimated)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 30 Sep 2025 (estimated)
- First posted
- 18 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Active comparator | Drug: Trastuzumab, Drug: Taxanes, Drug: PertuzumabTrastuzumab, Taxanes and Pertuzumab |
| Group B | Experimental | Drug: Trastuzumab, Drug: Taxanes, Drug: Tyrosine kinase inhibitorTrastuzumab, Taxanes and TKIs |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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)
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrastuzumabAlso: Herceptin8 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. | Drug | Group A, Group B |
| TaxanesAlso: Docetaxel, Paclitaxel, Paclitaxel (Albumin bound), Paclitaxel LiposomeDocetaxel: 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 | Drug | Group A, Group B |
| PertuzumabAlso: Perjeta840 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. | Drug | Group A |
| Tyrosine kinase inhibitorAlso: Pyrotinib, Neratinib, TucatinibPyrotinib: 400mg po within 30 minutes after a meal, QD, every 3 weeks Neratinib: 240mg po QD, every 3 weeks Tucatinib: 300mg po Q12H | Drug | Group B |
Primary outcome
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)
6 secondary outcomes
Objective Response Rate 2 (ORR2)
Time frame: up to 3 years
Progression-free Survival (PFS)
Time frame: up to 3 years
Overall Survival (OS)
Time frame: up to 3 years
Clinical benefit rate (CBR)
Time frame: up to 3 years
Disease control rate (DCR)
Time frame: up to 3 years
Peripheral neurotoxicity
Time frame: 30 days after last treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xuexin He, MD principal investigator
Second Affiliated Hospital, Zhejiang University, School of Medicine
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trastuzumab, Taxanes and Pertuzumab in people with HER2-positive Breast Cancer and Brain Metastases, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xuexin He, MD (18329139569 ext. 86, xuexinhe@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2021.