Breast Cancer FemalePhase 2PyrotinibNCT03910712
Pyrotinib Combined With Trastuzumab and AI in the First-line Treatment of HER2 Positive/ HR Positive MBC
A Phase 2 study testing Pyrotinib, Trastuzumab and Aromatase inhibitor in people with Breast Cancer Female and HER2-positive Breast Cancer, run by Peking Union Medical College Hospital.
Trial summary
This study is a randomized, open-label, phase II study, comparing the efficacy and safety of trastuzumab plus aromatase inhibitors, with or without pyrotinib, in the treatment of HR (hormone receptor)+/HER2 (human epidermal growth factor receptor 2) + MBC and inoperable LABC patients. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer Female, HER2-positive Breast Cancer, Hormone Receptor Positive Malignant Neoplasm of Breast
- What is being tested?
- Pyrotinib, Trastuzumab and Aromatase inhibitor
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2019to 1 Dec 2023
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age≥18 years, female;
- Postmenopausal or pre-menopausal with ovarian function suppression;
- At least one measurable lesion evaluable according to Response Evaluation Criteria In Solid Tumors Version 1.1;
- Metastatic or inoperable local advanced breast cancer;
- HER2-positive breast cancer;
- HR-positive breast cancer;
- LVEF ≥50%;
Who cannot join
- Previous systemic non-hormonal anticancer therapy in the metastatic or advanced breast cancer setting;
- Received endocrine therapy within 7 days before randomization;
- Uncontrolled central nervous system metastases;
- Disease-free interval from completion of adjuvant/neo-adjuvant systemic non-hormonal treatment to recurrence of within 6 months.
- Other malignancies within the last 3 years, except for carcinoma in situ of the cervix or basal cell carcinoma.
- Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
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- Severe organ dysfunction as assessed by signs and symptoms, laboratory studies and rapid progression of disease, which leading to a clinical indication for chemotherapy.
- History of CHF of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal supraventricular tachycardia);
- History of myocardial infarction within 6 months of randomization
- History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
- Pregnant or lactating women;
- QT interval>470 ms；
- Serious concomitant diseases (including severe hypertension, severe diabetes, active infection, thyroid disease, etc.) that are harmful to the patient's safety or affect the patient's completion of the study;
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Randomized, Open-label Study of First Line Pyrotinib, Trastuzumab With an Aromatase Inhibitors, in the Treatment of HER2 Positive and HR Positive Metastatic or Inoperable Locally Advanced Breast Cancer
This study is a randomized, open-label, phase II study, comparing the efficacy and safety of trastuzumab plus aromatase inhibitors, with or without pyrotinib, in the treatment of HR (hormone receptor)+/HER2 (human epidermal growth factor receptor 2) + MBC and inoperable LABC patients.
Read the detailed description
This is a randomized, two-arm, open-label, multicenter phase II trial. Our primary purpose is to compare that PFS of patients with trastuzumab, AI plus pyrotinib and trastuzumab plus an AI for HER2-positive and hormone receptor-positive MBC or locally advanced breast cancer (LABC).
Eligible patients will randomized to a ratio of 1:1 to pyrotinib+ trastuzumab + aromatase inhibitor (experimental group) or trastuzumab+aromatase inhibitor (control group). Stratification factors were 1)time since adjuvant hormone therapy (<=12 months/>12 months/no prior hormone therapy); 2) lesion (visceral; non-visceral).
In treatment period, patients will be administrated trastuzumab plus aromatase inhibitors, with or without pyrotinib, every 21 days for 1 cycle, until disease progression, toxicity intolerance, withdrawal of informed consent, patients judged must be terminated study termination.
The imaging evaluation was performed according to the RECIST 1.1 criteria every 6 weeks.
- Conditions
- Breast Cancer Female, HER2-positive Breast Cancer, Hormone Receptor Positive Malignant Neoplasm of Breast, Metastatic Breast Cancer, Breast Diseases, Hormone Receptor Positive Tumor
- Being tested
- Pyrotinib, Trastuzumab, Aromatase inhibitor
- Keywords
- MBC, Pyrotinib, Trastuzumab, First line, HER2
- Medical subject headings
- Breast Neoplasms, Breast Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PyrotinibDrug
Also called Study drug
Pyrotinib were administered 400 mg orally daily. Oral administration within 30 minutes after breakfast, and continuous administration for 21 days for 1 cycle.
TrastuzumabDrug
Also called Herceptin®
Trastuzumab were administered every 3 weeks intravenously (8 mg/kg loading doses followed by 6 mg/kg maintenance doses).
Aromatase inhibitorDrug
Also called anastrozole, letrozole or exemestane
The investigator chose an aromatase inhibitor (either anastrozole, letrozole or exemestane 1 mg/2.5 mg/25 mg), once daily, oral.
| Study group | Role | What they receive |
|---|---|---|
| Pyrotinib and trastuzumab plus aromatase inhibitor | Experimental | Participants will receive pyrotinib in combination with trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. Receives: Drug: Pyrotinib; Drug: Trastuzumab; Drug: Aromatase inhibitor |
| Trastuzumab plus aromatase inhibitor | Active comparator | Participants will receive trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. Receives: Drug: Trastuzumab; Drug: Aromatase inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS)
PFS was defined as the time from randomization to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or death from any cause, whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
The PFS will be will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median PFS, hazard ratio with appropriate confidence intervals will be reported.
Measured: From randomization to 36 month
Secondary outcomes (8)
Overall Survival (OS)
Overall Survival (OS), defined as the time from the date of randomization to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication and participants with no post-baseline information were censored at the date of randomization.
The OS will be will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median OS, hazard ratio with appropriate confidence intervals will be reported.
Measured: From randomization to 36 month
Objective Overall Response Rate (ORR)
ORR was defined as percentage of participants with best (confirmed) overall response (BOR) of either CR or PR. ORR was assessed by the investigator according to RECIST version 1.1 and is based on BOR, which is defined as best response recorded from start of study treatment until disease progression/recurrence or death. Participants needed to have two consecutive assessments of PR or CR to be a responder. Only participants with measurable disease at baseline were included in the analysis of BOR and who did not have any evaluable post-baseline assessments were classified as not evaluable.
The ORR will be reported by percentage with each arms and appropriate confidence intervals.
Measured: From randomization to 36 month
Duration of Response (DoR)
DoR is defined as date of initial confirmed PR/CR until date of progressive disease or death from any cause. PR or CR or SD is according to RECIST version 1.1.
The DoR will be estimated using Kaplan-Meier method. Kaplan-Meier curves, median DoR, hazard ratio with appropriate confidence intervals will be reported.
Measured: From randomization to 36 month
Time to Response (TTR)
Time to Response (TTR), defined as the time from the date of randomization to the date of first CR or PR. CR or PR is according to RECIST version 1.1.
The TTR will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median TTR, hazard ratio with appropriate confidence intervals will be reported.
Measured: From randomization to 36 month
Clinical Benefit Response (CBR)
CBR is percentage of participants with best (confirmed) PR or CR or SD for at least 6 months. PR or CR or SD is according to RECIST version 1.1.
The CBR will be reported by percentage with each arms and appropriate confidence intervals.
Measured: From randomization to 36 month
Adverse events (AEs)
AEs were graded according to the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0.3.
In general, AEs are graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE.
The type, grade and frequency of AEs will be reported.
Measured: From screening phase until AEs returns to Grade 0-1 or baseline
Quality of Life (QoL) by FACT-B
QoL was assessed using Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B). FACT-B is a 37-item questionnaire with 5 subscales assessing physical, social, emotional, and functional well-being, as well as a breast cancer specific subscale.
FACT-B questionnaires were completed by patients on screening phase (baseline) and each 6 weeks after randomization. Mean change from baseline of FACT-B scores by each visit for each arms will be reported.
Measured: From randomization to 36 month
Quality of Life (QoL) by EQ-5D
QoL was assessed using EuroQoL 5-Dimensions (EQ-5D). EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments.
EQ-5D questionnaires were completed by patients on screening phase (baseline) and each 6 weeks after randomization. Mean change from baseline of EQ-5D scores by each visit for each arms will be reported.
Measured: From randomization to 36 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2019
- Study start1 Jun 2019 (estimated)
- Primary completion1 Jun 2022 (estimated)
- Study completion1 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast Cancer FemaleStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe 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
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Qiang SUN, Peking Union Medical College Hospital
- Investigators
- Qiang Sun, M.D., Study chair, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03910712
- Sponsor's protocol ID
- BREAST-Pyrotinib
- Acronym
- Pyrotinib
- Status last verified
- Apr 2019
- First submitted
- 3 Apr 2019
- Last updated
- 10 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wang C, Lin Y, Zhou Y, Mao F, Zhu H, Guan J, Zhang X, Shen S, Huang X, Chen C, Yao R, Zhao J, Sun Q. Pyrotinib with trastuzumab and aromatase inhibitors as first-line treatment for HER2 positive and hormone receptor positive metastatic or locally advanced breast cancer: study protocol of a randomized controlled trial. BMC Cancer. 2020 Jul 13;20(1):653. doi: 10.1186/s12885-020-07143-2.
PubMed 32660609
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label Study of First Line Pyrotinib, Trastuzumab With an Aromatase Inhibitors, in the Treatment of HER2 Positive and HR Positive Metastatic or Inoperable Locally Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT03910712
- Acronym / sponsor ID
- Pyrotinib / BREAST-Pyrotinib
- Conditions
- Breast Cancer Female, HER2-positive Breast Cancer, Hormone Receptor Positive Malignant Neoplasm of Breast, Metastatic Breast Cancer, Breast Diseases, Hormone Receptor Positive Tumor
- Keywords
- MBC, Pyrotinib, Trastuzumab, First line, HER2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- 1 Jun 2019 (estimated)
- Primary completion
- 1 Jun 2022 (estimated)
- Study completion
- 1 Dec 2023 (estimated)
- First posted
- 10 Apr 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 a randomized, open-label, phase II study, comparing the efficacy and safety of trastuzumab plus aromatase inhibitors, with or without pyrotinib, in the treatment of HR (hormone receptor)+/HER2 (human epidermal growth factor receptor 2) + MBC and inoperable LABC patients.
Detailed description
This is a randomized, two-arm, open-label, multicenter phase II trial. Our primary purpose is to compare that PFS of patients with trastuzumab, AI plus pyrotinib and trastuzumab plus an AI for HER2-positive and hormone receptor-positive MBC or locally advanced breast cancer (LABC).
Eligible patients will randomized to a ratio of 1:1 to pyrotinib+ trastuzumab + aromatase inhibitor (experimental group) or trastuzumab+aromatase inhibitor (control group). Stratification factors were 1)time since adjuvant hormone therapy (<=12 months/>12 months/no prior hormone therapy); 2) lesion (visceral; non-visceral).
In treatment period, patients will be administrated trastuzumab plus aromatase inhibitors, with or without pyrotinib, every 21 days for 1 cycle, until disease progression, toxicity intolerance, withdrawal of informed consent, patients judged must be terminated study termination.
The imaging evaluation was performed according to the RECIST 1.1 criteria every 6 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pyrotinib and trastuzumab plus aromatase inhibitor | Experimental | Drug: Pyrotinib, Drug: Trastuzumab, Drug: Aromatase inhibitorParticipants will receive pyrotinib in combination with trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. |
| Trastuzumab plus aromatase inhibitor | Active comparator | Drug: Trastuzumab, Drug: Aromatase inhibitorParticipants will receive trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age≥18 years, female;
- Postmenopausal or pre-menopausal with ovarian function suppression;
- At least one measurable lesion evaluable according to Response Evaluation Criteria In Solid Tumors Version 1.1;
- Metastatic or inoperable local advanced breast cancer;
- HER2-positive breast cancer;
Key exclusion criteria (13 listed)
- Previous systemic non-hormonal anticancer therapy in the metastatic or advanced breast cancer setting;
- Received endocrine therapy within 7 days before randomization;
- Uncontrolled central nervous system metastases;
- Disease-free interval from completion of adjuvant/neo-adjuvant systemic non-hormonal treatment to recurrence of within 6 months.
- Other malignancies within the last 3 years, except for carcinoma in situ of the cervix or basal cell carcinoma.
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 |
|---|---|---|
| PyrotinibAlso: Study drugPyrotinib were administered 400 mg orally daily. Oral administration within 30 minutes after breakfast, and continuous administration for 21 days for 1 cycle. | Drug | Pyrotinib and trastuzumab plus aromatase inhibitor |
| TrastuzumabAlso: Herceptin®Trastuzumab were administered every 3 weeks intravenously (8 mg/kg loading doses followed by 6 mg/kg maintenance doses). | Drug | Pyrotinib and trastuzumab plus aromatase inhibitor, Trastuzumab plus aromatase inhibitor |
| Aromatase inhibitorAlso: anastrozole, letrozole or exemestaneThe investigator chose an aromatase inhibitor (either anastrozole, letrozole or exemestane 1 mg/2.5 mg/25 mg), once daily, oral. | Drug | Pyrotinib and trastuzumab plus aromatase inhibitor, Trastuzumab plus aromatase inhibitor |
Primary outcome
Progression-Free Survival (PFS)
Time frame: From randomization to 36 month
PFS was defined as the time from randomization to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or death from any cause, whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. The PFS will be will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median PFS, hazard ratio with appropriate confidence intervals will be reported.
8 secondary outcomes
Overall Survival (OS)
Time frame: From randomization to 36 month
Objective Overall Response Rate (ORR)
Time frame: From randomization to 36 month
Duration of Response (DoR)
Time frame: From randomization to 36 month
Time to Response (TTR)
Time frame: From randomization to 36 month
Clinical Benefit Response (CBR)
Time frame: From randomization to 36 month
Adverse events (AEs)
Time frame: From screening phase until AEs returns to Grade 0-1 or baseline
Quality of Life (QoL) by FACT-B
Time frame: From randomization to 36 month
Quality of Life (QoL) by EQ-5D
Time frame: From randomization to 36 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2019.
- Derived from this study: PubMed 32660609Wang C, Lin Y, Zhou Y, Mao F, Zhu H, Guan J, Zhang X, Shen S, Huang X, Chen C, Yao R, Zhao J, Sun Q. Pyrotinib with trastuzumab and aromatase inhibitors as first-line treatment for HER2 positive and hormone receptor positive metastatic or locally advanced breast cancer: study protocol of a randomized controlled trial. BMC Cancer. 2020 Jul 13;20(1):653. doi: 10.1186/s12885-020-07143-2.
- Individual participant dataSharing planned: No
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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.
Qiang Sun, M.D. study chair
Peking Union Medical College Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pyrotinib, Trastuzumab and Aromatase inhibitor in people with Breast Cancer Female and HER2-positive Breast Cancer, run by Peking Union Medical College Hospital.
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 7 inclusion and 13 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 10 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
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 Qiang Sun, M.D. (86-10-69158721, sunqiangpumch@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) (time frame: From randomization to 36 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03910712, which also lists 1 linked publication.
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 10 Apr 2019.