HER2-positive Breast CancerPhase 2HER2BATNCT04158947
A Study of HER2+ Breast Cancer Patients With Active Brain Metastases Treated With Afatinib & T-DM1 vs. T-DM1 Alone
A Phase 2 study testing Afatinib and T-DM1 in people with HER2-positive Breast Cancer and Brain Metastases, run by xuexin he at 4 sites in China.
Trial summary
This study is being done for the following reasons: The study has two parts. The purpose of the first part (Phase I) of the study is to find out the highest dose of Afatinib that can be given safely with T-DM1. 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?
- Afatinib and T-DM1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 4 sitesChina
- Study dates
- 10 May 2020to 31 Mar 2024
- 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 old
- Histologically or cytologically confirmed HER2-positive (IHC 3+ or ISH+) breast cancer
- Patients with HER2 positive breast cancer with a documented central nervous system (CNS) recurrence/progression (by imaging) during or after a HER2 inhibitor (Trastuzumab and/or Lapatinib, Pyrotinib, Tucatinib) 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
- 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 2
- 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
- Suffering cerebral hernia
- 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 inhibitor other than Lapatinib, Neratinib, Pyrotinib and Tucatinib, such as Afatinib, Erlotinib, Icotinib, Gefitinib and Osimertinib
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- 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 TDM1 or Afatinib or the excipients of any of the trial drugs
- Significant chronic or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn's disease, malabsorption or Common Terminology Criteria (CTC) grade =2 diarrhoea of any aetiology
- 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
4 sites in 1 country.
China4 sites, 4 recruiting
- Not yet recruiting
Peking University International Hospital
Beijing, Beijing Municipality, 102206
Lingling Zhang, MD, +86-010-69006666
- Not yet recruiting
Sun Yat-sen University Cancer Center (SYSUCC)
Guangzhou, Guangdong, 510000
Chengcheng Guo, MD, +86-020-87343088
- Recruiting
The Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU)
Hangzhou, Zhejiang, 310000
xuexin he, MD, +86-0571-87784795, xuexinhe@zju.edu.cn
xuexin he, MD
- Not yet recruiting
Kiang Wu Hospital
Macao, Macao, 820002
Yabing Cao, MD, +86-00853-28371333
About this study
Official title: A Randomized Study of HER2+ Breast Cancer Patients With Active Refractory Brain Metastases Treated With Afatinib in Combination With T-DM1 vs. T-DM1 Alone
This study is being done for the following reasons:
The study has two parts. The purpose of the first part (Phase I) of the study is to find out the highest dose of Afatinib that can be given safely with T-DM1.
The purpose of the second part of the study (Phase II) is to find out whether the dose of Afatinib with T-DM1 determined in Phase I will keep breast cancer from getting worse for a period of time.
Read the detailed description
This is a prospective, randomized, 2-arm, multicenter study to compare the safety and efficiency of T-DM1 + Afatinib versus T-DM1 in HER2-positive breast cancer patients with active refractory brain metastases. This study will be divided into two phases. The purpose of Phase I is to find out the highest dose of Afatinib that can be given safely with T-DM1. 3 ~ 24 eligible subjects will be enrolled in the study. The purpose of Phase II is to find out whether the dose of Afatinib with T-DM1 determined in Phase I will keep subjects from getting worse for a period of time. The estimated ORR is 17.9 percent in the control group, hypothesis Afatinib can improve the prognosis of subjects, so objective respond rate (ORR) of experimental group is increased by 30 percent, with alpha = 0.025 (unilateral), beta = 0.1. The ratio of the experimental group and control group is 1:1, assuming a 5 percent loss rate. As a result, calculating by PASS 11 software, approximately 106 subjects will be enrolled, with 53 cases in the experimental group, and 53 cases in the control group.
- Conditions
- HER2-positive Breast Cancer, Brain Metastases
- Being tested
- Afatinib, T-DM1
- Keywords
- HER2-positive Breast Cancer, Brain metastases, T-DM1, Afatinib
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfatinibDrug
Also called BIBW 2992
Dose-escalation Phase (Phase I) - Afatinib Dose-escalation will proceed on the basis of dose limiting toxicity (DLT) during Cycle 1 starting at 20 mg/day.
Dose level 1: 20 mg/day; Dose level 2: 30 mg/day; Dose level 3: 40 mg/day; Dose level 4: 50 mg/day.
Dose-evaluation Phase (Phase II) - Patients will receive the highest dose of Afatinib with T-DM1 found in Phase I as study therapy
T-DM1Drug
Also called Trastuzumab emtansine
Dose-escalation Phase (Phase I) - Trastuzumab emtansine (T-DM1) will be given at 3.6 mg/kg IV Day 1 every 21 days.
Dose-evaluation Phase (Phase II) - Trastuzumab emtansine (T-DM1) will be given at 3.6 mg/kg IV Day 1 every 21 days.
| Study group | Role | What they receive |
|---|---|---|
| T-DM1 + Afatinib | Experimental | Trastuzumab emtansine (T-DM1) : 3.6 mg/kg IV Day 1 every 21 days.
Afatinib: the highest dose of Afatinib with T-DM1 found in Phase I, po every day Receives: Drug: Afatinib; Drug: T-DM1 |
| T-DM1 | Active comparator | Trastuzumab emtansine (T-DM1) :3.6 mg/kg IV Day 1 every 21 days. Receives: Drug: T-DM1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of T-DM1 and Afatinib to determine the recommended Phase II dose (RP2D)
If 1 of 3 patients in this cohort experiences a dose limiting toxicity (DLT), 3 more patients will be added at the same dose level. If 0 of 3 initial patients or 1 of 6 patients in an expanded cohort experiences a DLT, the dose for the next cohort will be escalated to dose level 2; otherwise, the combination will be considered too toxic.
Measured: 21 days
Objective Response Rate(ORR)
The sum of complete response (CR) rate and partial response (PR) rate by measurement of target lesions
Measured: From the start of study therapy through study therapy stops, approximately 3 months
Secondary outcomes (1)
Progression-free Survival (PFS)
PFS is defined as time from randomization to disease progression or death, whichever occurs first, including central nervous system lesions and external central nervous system lesions
Measured: From the start of study therapy through study therapy stops, approximately 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2019
- Study start10 May 2020 (estimated)
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Mar 2024 (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.
- 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
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- xuexin he
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, xuexin he, Second Affiliated Hospital, Zhejiang University, School of Medicine
- Investigators
- xuexin he, MD, Study director, The Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04158947
- Sponsor's protocol ID
- HER2BAT
- Acronym
- HER2BAT
- Status last verified
- May 2020
- First submitted
- 2 Nov 2019
- Last updated
- 12 May 2020
- 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 12 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Study of HER2+ Breast Cancer Patients With Active Refractory Brain Metastases Treated With Afatinib in Combination With T-DM1 vs. T-DM1 Alone
- ClinicalTrials.gov ID
- NCT04158947
- Acronym / sponsor ID
- HER2BAT / HER2BAT
- Conditions
- HER2-positive Breast Cancer, Brain Metastases
- Keywords
- HER2-positive Breast Cancer, Brain metastases, T-DM1, Afatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- xuexin heUniversity, hospital or other
- Study start
- 10 May 2020 (estimated)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Mar 2024 (estimated)
- First posted
- 12 Nov 2019 (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 study is being done for the following reasons:
The study has two parts. The purpose of the first part (Phase I) of the study is to find out the highest dose of Afatinib that can be given safely with T-DM1.
The purpose of the second part of the study (Phase II) is to find out whether the dose of Afatinib with T-DM1 determined in Phase I will keep breast cancer from getting worse for a period of time.
Detailed description
This is a prospective, randomized, 2-arm, multicenter study to compare the safety and efficiency of T-DM1 + Afatinib versus T-DM1 in HER2-positive breast cancer patients with active refractory brain metastases. This study will be divided into two phases. The purpose of Phase I is to find out the highest dose of Afatinib that can be given safely with T-DM1. 3 ~ 24 eligible subjects will be enrolled in the study. The purpose of Phase II is to find out whether the dose of Afatinib with T-DM1 determined in Phase I will keep subjects from getting worse for a period of time. The estimated ORR is 17.9 percent in the control group, hypothesis Afatinib can improve the prognosis of subjects, so objective respond rate (ORR) of experimental group is increased by 30 percent, with alpha = 0.025 (unilateral), beta = 0.1. The ratio of the experimental group and control group is 1:1, assuming a 5 percent loss rate. As a result, calculating by PASS 11 software, approximately 106 subjects will be enrolled, with 53 cases in the experimental group, and 53 cases in the control group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| T-DM1 + Afatinib | Experimental | Drug: Afatinib, Drug: T-DM1Trastuzumab emtansine (T-DM1) : 3.6 mg/kg IV Day 1 every 21 days. Afatinib: the highest dose of Afatinib with T-DM1 found in Phase I, po every day |
| T-DM1 | Active comparator | Drug: T-DM1Trastuzumab emtansine (T-DM1) :3.6 mg/kg IV Day 1 every 21 days. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Patients provided written informed consent
- Women aged 18-75 years old
- Histologically or cytologically confirmed HER2-positive (IHC 3+ or ISH+) breast cancer
- Patients with HER2 positive breast cancer with a documented central nervous system (CNS) recurrence/progression (by imaging) during or after a HER2 inhibitor (Trastuzumab and/or Lapatinib, Pyrotinib, Tucatinib) based therapy
- At least one measurable and progressive lesion in the CNS (≥10 mm on T1-weighted, gadolinium-enhanced MRI)
Key exclusion criteria (16 listed)
- Lack of histological or cytological confirmation of HER2-positive (IHC 3+ or ISH-positive) breast cancer
- Suffering cerebral hernia
- 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
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 |
|---|---|---|
| AfatinibAlso: BIBW 2992Dose-escalation Phase (Phase I) - Afatinib Dose-escalation will proceed on the basis of dose limiting toxicity (DLT) during Cycle 1 starting at 20 mg/day. Dose level 1: 20 mg/day; Dose level 2: 30 mg/day; Dose level 3: 40 mg/day; Dose level 4: 50 mg/day. Dose-evaluation Phase (Phase II) - Patients will receive the highest dose of Afatinib with T-DM1 found in Phase I as study therapy | Drug | T-DM1 + Afatinib |
| T-DM1Also: Trastuzumab emtansineDose-escalation Phase (Phase I) - Trastuzumab emtansine (T-DM1) will be given at 3.6 mg/kg IV Day 1 every 21 days. Dose-evaluation Phase (Phase II) - Trastuzumab emtansine (T-DM1) will be given at 3.6 mg/kg IV Day 1 every 21 days. | Drug | T-DM1, T-DM1 + Afatinib |
Primary outcome
Safety and tolerability of T-DM1 and Afatinib to determine the recommended Phase II dose (RP2D)
Time frame: 21 days
If 1 of 3 patients in this cohort experiences a dose limiting toxicity (DLT), 3 more patients will be added at the same dose level. If 0 of 3 initial patients or 1 of 6 patients in an expanded cohort experiences a DLT, the dose for the next cohort will be escalated to dose level 2; otherwise, the combination will be considered too toxic.
Objective Response Rate(ORR)
Time frame: From the start of study therapy through study therapy stops, approximately 3 months
The sum of complete response (CR) rate and partial response (PR) rate by measurement of target lesions
1 secondary outcome
Progression-free Survival (PFS)
Time frame: From the start of study therapy through study therapy stops, approximately 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2020.
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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 study director
The Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU)
4 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 Afatinib and T-DM1 in people with HER2-positive Breast Cancer and Brain Metastases, run by xuexin he at 4 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 22 inclusion and 16 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 12 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 (+86-18329139569, xuexinhe@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of T-DM1 and Afatinib to determine the recommended Phase II dose (RP2D) (time frame: 21 days). The study lists 2 primary outcomes in all. 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 12 May 2020.