Breast CancerPhase 2NCT05430347
Clinical Study of Pyrotinib in Neoadjuvant Therapy of HR-positive and HER2-positive Breast Cancer
A Phase 2 study testing Neoadjuvant therapy: TCbHPy and Neoadjuvant therapy: TCbHP in people with Breast Cancer, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial summary
Due to neoadjuvant therapy with trastuzumab and pertuzumab is less effective for HR+/HER2+ breast cancer, and the PHEDRA Clinical Study subgroup analysis showed that the addition of pyrotinib to trastuzumab more than doubled pCR rates in HR+/HER2+ patients. Read more about this study
- Who is it for?
- Ages 20 to 70 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Neoadjuvant therapy: TCbHPy and Neoadjuvant therapy: TCbHP
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- 15 Apr 2023to 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 20 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women aged 18-70 with breast cancer;
- Pathologically confirmed unilateral invasive ductal carcinoma (with or without intraductal carcinoma components);
- Proposed to receive neoadjuvant therapy;
- Positive ER and/or PgR (defined as ≥10% positive immunohistochemical test);
- HER2 positive (defined as IMMUNOHISTOchemical HER2 ++, or HER2 ++ and in situ hybridization (ISH) results in HER2 gene amplification);
- There is no evidence of metastasis in clinical or imaging;
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- ECOG score 0 or 1;
- White blood cell count ≥3.5×109/L, neutrophil count ≥2×109/L, platelet count ≥100×109/L and hemoglobin ≥90 g/L before neoadjuvant therapy;
- Before neoadjuvant therapy, AST and ALT < 1.5 times the upper limit of normal value, alkaline phosphatase < 2.5 times the upper limit of normal value, total bilirubin < 1.5 times the upper limit of normal value; Serum creatinine < 1.5 times the upper limit of normal value;
- LVEF≥55% on 2d echocardiography before neoadjuvant therapy;
- Signed informed consent.
Who cannot join
- Clinical or imaging suspicion of lateral breast malignancy has not been confirmed;
- Prior malignancy (except basal cell carcinoma of the skin and carcinoma in situ of the cervix), including contralateral breast cancer;
- The patient has been enrolled in other clinical trials;
- Patients suffering from serious systemic diseases and/or uncontrollable infections cannot be enrolled in the study;
- Severe cardiovascular and cerebrovascular diseases (e.g., unstable angina pectoris, chronic heart failure, uncontrolled hypertension > 150/90mmHg, myocardial infarction or cerebrovascular accident) within the first 6 months of randomization;
- Have a history of blood system diseases, especially platelet-related diseases;
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- Patients with previous intestinal inflammation, intestinal dysfunction, severe diarrhea and constipation;
- People who are known to be allergic to chemotherapy drugs, targeted drugs or TKI drugs;
- Women of childbearing age refuse contraception during treatment and within 8 weeks after completion of treatment;
- Pregnant and lactation women;
- positive pregnancy test before drug use after joining the test;
- Mental illness, cognitive impairment, inability to understand the test protocol and side effects, inability to complete the test protocol and follow-up workers (systematic evaluation is required before the trial is enrolled);
- Persons without personal freedom and independent capacity for civil conduct.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multicenter Phase II Clinical Study of Pyrotinib or Pertuzumab Combined With Docetaxel, Carboplatin, and Trastuzumab in Neoadjuvant Therapy for HR-positive, HER2-positive Breast Cancer
Due to neoadjuvant therapy with trastuzumab and pertuzumab is less effective for HR+/HER2+ breast cancer, and the PHEDRA Clinical Study subgroup analysis showed that the addition of pyrotinib to trastuzumab more than doubled pCR rates in HR+/HER2+ patients. our research group proposed a hypothesis that pyrotinib may be more advantageous for HR+/HER2+ breast cancer. Therefore, our center intends to carry out a multi-center, randomized controlled, prospective clinical study to compare the efficacy of pyrotinib or pertuzumab combined with docetaxel, carboplatin and trastuzumab in neoadjuvant therapy for patients with HR+/HER2+ breast cancer, and to conduct a comparative study on the safety.
Read the detailed description
Different anti-HER2-targeting drugs act on different parts and types of HER2 molecules, so their mechanisms and effects are different. Trastuzumab and pertuzumab are the most commonly used anti-HER2 targeting drugs, which target the extracellular segment of THE HER2 molecule. The major guidelines recommend the use of trastuzumab and pertuzumab in the use of neoadjuvant therapy with a two-target regimen. Another commonly used class of anti-HER2-targeting drugs are Tyrosine kinase inhibitors (TKI), which target the intracellular segment of the HER2 molecule. Not only that, take domestically developed pyrotinib as an example, in addition to targeting HER2, it also targets HER1 and HER4. Because of the different mechanisms of action, TKI is still effective in patients with trastuzumab and/or pertuzumab resistant relapsing metastasis. To investigate the efficacy of pyrotinib in neoadjuvant therapy, a prospective, randomized, double-blind, multicenter clinical trial, the PHEDRA Clinical Study, was conducted in China. Results presented at the 2021 ASCO Meeting showed that addition of pyrotinib to trastuzumab also significantly increased tpCR rate (22.0% vs 41.0%; P < 0.0001), and the pCR rate was similar to trastuzumab + pertuzumab double target (39.3% for Neosphere and Peony). Based on these results, neoadjuvant therapy regimens with trastuzumab and TKI have been included in the 2022 CSCO guidelines.
Of note, there were also differences in Hormone Receptor (HR) status in patients with HER2-positive breast cancer. After neoadjuvant chemotherapy combined with trastuzumab and pertuzumab double-target therapy, the pCR rate of HR-/HER2+ breast cancer was higher than HR+/HER2+ breast cancer. In contrast, a PHEDRA subgroup analysis showed that the addition of pyrotinib to trastuzumab more than doubled pCR rates in HR+/HER2+ patients (29.9% vs 12.2%) . In addition, in another adjunctive study of TKI drug neratinib, subgroup results also suggested that neratinib had a better effect on HR+/HER2+.
Based on the above results, our research group proposed a hypothesis that TKI drugs may be more advantageous for HR+/HER2+ breast cancer. Therefore, our center intends to carry out a multi-center, randomized controlled, prospective clinical study to compare the efficacy of pyrotinib or pertuzumab combined with docetaxel, carboplatin and trastuzumab in neoadjuvant therapy for patients with HR+/HER2+ breast cancer, and to conduct a comparative study on the safety.
- Conditions
- Breast Cancer
- Being tested
- Neoadjuvant therapy: TCbHPy, Neoadjuvant therapy: TCbHP
- Keywords
- HR+/HER2+ Breast cancer, Neoadjuvant therapy, pyrotinib
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neoadjuvant therapy: TCbHPyCombination product
Pyrotinib combined with docetaxel, carboplatin and trastuzumab (TCbHPy) for neoadjuvant therapy of HR+/HER2+ breast cancer
Neoadjuvant therapy: TCbHPCombination product
Pertuzumab combined with docetaxel, carboplatin and trastuzumab (TCbHP) for neoadjuvant therapy of HR+/HER2+ breast cancer
| Study group | Role | What they receive |
|---|---|---|
| TCbHPy*6 | Experimental | Pyrotinib combined with docetaxel, carboplatin and trastuzumab for 6 cycles (Every three weeks).
T (Docetaxel 100 mg/m2, d1) C (Carboplatin, AUC 6, D1) H (Trastuzumab, 8 mg/kg for the first dose, 6 mg/kg for the rest, D1) Py (pyrotinib 400mg, qD, D1-21) Receives: Combination Product: Neoadjuvant therapy: TCbHPy |
| TCbHP*6 | Active comparator | Pertuzumab combined with docetaxel, carboplatin and trastuzumab for 6 cycles (Every three weeks).
T (Docetaxel 100 mg/m2, d1) C (Carboplatin, AUC 6, D1) H (Trastuzumab, 8 mg/kg for the first dose, 6 mg/kg for the rest, D1) P (Pertuzumab, 840mg for the first dose, 420mg for the rest, D1)) Receives: Combination Product: Neoadjuvant therapy: TCbHP |
What is being measured
The primary outcome is the main question the study is designed to answer.
tpCR rate (ypT0/is ypN0)
Pathological complete response rate after neoadjuvant ( both breast and axillary lymph nodes, in which the breast may have residual carcinoma in situ)
Measured: 1 month after surgery
Secondary outcomes (2)
iDFS
invasive Disease Free Survival
Measured: 3 years
EFS
Event Free Survival
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2022
- Study start15 Apr 2023 (estimated)
- Primary completion15 Jun 2025 (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 Breast CancerStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical UniversityThe 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
- Model description
- The treatment regimen of the experimental group was pyrotinib combined with docetaxel, carboplatin and trastuzumab, while the treatment regimen of the control group was pertuzumab combined with docetaxel, carboplatin and trastuzumab (the control group was standard treatment). Surgical treatment was performed after 6 courses of neoadjuvant therapy
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05430347
- Sponsor's protocol ID
- Pyrotinib neoadjuvant
- Status last verified
- Feb 2023
- First submitted
- 12 Jun 2022
- Last updated
- 21 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase II Clinical Study of Pyrotinib or Pertuzumab Combined With Docetaxel, Carboplatin, and Trastuzumab in Neoadjuvant Therapy for HR-positive, HER2-positive Breast Cancer
- ClinicalTrials.gov ID
- NCT05430347
- Acronym / sponsor ID
- Pyrotinib neoadjuvant
- Conditions
- Breast Cancer
- Keywords
- HR+/HER2+ Breast cancer, Neoadjuvant therapy, pyrotinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Study start
- 15 Apr 2023 (estimated)
- Primary completion
- 15 Jun 2025 (estimated)
- Study completion
- 30 Sep 2025 (estimated)
- First posted
- 24 Jun 2022 (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.
Due to neoadjuvant therapy with trastuzumab and pertuzumab is less effective for HR+/HER2+ breast cancer, and the PHEDRA Clinical Study subgroup analysis showed that the addition of pyrotinib to trastuzumab more than doubled pCR rates in HR+/HER2+ patients. our research group proposed a hypothesis that pyrotinib may be more advantageous for HR+/HER2+ breast cancer. Therefore, our center intends to carry out a multi-center, randomized controlled, prospective clinical study to compare the efficacy of pyrotinib or pertuzumab combined with docetaxel, carboplatin and trastuzumab in neoadjuvant therapy for patients with HR+/HER2+ breast cancer, and to conduct a comparative study on the safety.
Detailed description
Different anti-HER2-targeting drugs act on different parts and types of HER2 molecules, so their mechanisms and effects are different. Trastuzumab and pertuzumab are the most commonly used anti-HER2 targeting drugs, which target the extracellular segment of THE HER2 molecule. The major guidelines recommend the use of trastuzumab and pertuzumab in the use of neoadjuvant therapy with a two-target regimen. Another commonly used class of anti-HER2-targeting drugs are Tyrosine kinase inhibitors (TKI), which target the intracellular segment of the HER2 molecule. Not only that, take domestically developed pyrotinib as an example, in addition to targeting HER2, it also targets HER1 and HER4. Because of the different mechanisms of action, TKI is still effective in patients with trastuzumab and/or pertuzumab resistant relapsing metastasis. To investigate the efficacy of pyrotinib in neoadjuvant therapy, a prospective, randomized, double-blind, multicenter clinical trial, the PHEDRA Clinical Study, was conducted in China. Results presented at the 2021 ASCO Meeting showed that addition of pyrotinib to trastuzumab also significantly increased tpCR rate (22.0% vs 41.0%; P < 0.0001), and the pCR rate was similar to trastuzumab + pertuzumab double target (39.3% for Neosphere and Peony). Based on these results, neoadjuvant therapy regimens with trastuzumab and TKI have been included in the 2022 CSCO guidelines.
Of note, there were also differences in Hormone Receptor (HR) status in patients with HER2-positive breast cancer. After neoadjuvant chemotherapy combined with trastuzumab and pertuzumab double-target therapy, the pCR rate of HR-/HER2+ breast cancer was higher than HR+/HER2+ breast cancer. In contrast, a PHEDRA subgroup analysis showed that the addition of pyrotinib to trastuzumab more than doubled pCR rates in HR+/HER2+ patients (29.9% vs 12.2%) . In addition, in another adjunctive study of TKI drug neratinib, subgroup results also suggested that neratinib had a better effect on HR+/HER2+.
Based on the above results, our research group proposed a hypothesis that TKI drugs may be more advantageous for HR+/HER2+ breast cancer. Therefore, our center intends to carry out a multi-center, randomized controlled, prospective clinical study to compare the efficacy of pyrotinib or pertuzumab combined with docetaxel, carboplatin and trastuzumab in neoadjuvant therapy for patients with HR+/HER2+ breast cancer, and to conduct a comparative study on the safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The treatment regimen of the experimental group was pyrotinib combined with docetaxel, carboplatin and trastuzumab, while the treatment regimen of the control group was pertuzumab combined with docetaxel, carboplatin and trastuzumab (the control group was standard treatment). Surgical treatment was performed after 6 courses of neoadjuvant therapy
| Arm | Type | Receives |
|---|---|---|
| TCbHPy*6 | Experimental | Combination Product: Neoadjuvant therapy: TCbHPyPyrotinib combined with docetaxel, carboplatin and trastuzumab for 6 cycles (Every three weeks). T (Docetaxel 100 mg/m2, d1) C (Carboplatin, AUC 6, D1) H (Trastuzumab, 8 mg/kg for the first dose, 6 mg/kg for the rest, D1) Py (pyrotinib 400mg, qD, D1-21) |
| TCbHP*6 | Active comparator | Combination Product: Neoadjuvant therapy: TCbHPPertuzumab combined with docetaxel, carboplatin and trastuzumab for 6 cycles (Every three weeks). T (Docetaxel 100 mg/m2, d1) C (Carboplatin, AUC 6, D1) H (Trastuzumab, 8 mg/kg for the first dose, 6 mg/kg for the rest, D1) P (Pertuzumab, 840mg for the first dose, 420mg for the rest, D1)) |
Who may qualify
- Ages
- 20 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Women aged 18-70 with breast cancer;
- Pathologically confirmed unilateral invasive ductal carcinoma (with or without intraductal carcinoma components);
- Proposed to receive neoadjuvant therapy;
- Positive ER and/or PgR (defined as ≥10% positive immunohistochemical test);
- HER2 positive (defined as IMMUNOHISTOchemical HER2 ++, or HER2 ++ and in situ hybridization (ISH) results in HER2 gene amplification);
Key exclusion criteria (13 listed)
- Clinical or imaging suspicion of lateral breast malignancy has not been confirmed;
- Prior malignancy (except basal cell carcinoma of the skin and carcinoma in situ of the cervix), including contralateral breast cancer;
- The patient has been enrolled in other clinical trials;
- Patients suffering from serious systemic diseases and/or uncontrollable infections cannot be enrolled in the study;
- Severe cardiovascular and cerebrovascular diseases (e.g., unstable angina pectoris, chronic heart failure, uncontrolled hypertension > 150/90mmHg, myocardial infarction or cerebrovascular accident) within the first 6 months of randomization;
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 |
|---|---|---|
| Neoadjuvant therapy: TCbHPyPyrotinib combined with docetaxel, carboplatin and trastuzumab (TCbHPy) for neoadjuvant therapy of HR+/HER2+ breast cancer | Combination product | TCbHPy*6 |
| Neoadjuvant therapy: TCbHPPertuzumab combined with docetaxel, carboplatin and trastuzumab (TCbHP) for neoadjuvant therapy of HR+/HER2+ breast cancer | Combination product | TCbHP*6 |
Primary outcome
tpCR rate (ypT0/is ypN0)
Time frame: 1 month after surgery
Pathological complete response rate after neoadjuvant ( both breast and axillary lymph nodes, in which the breast may have residual carcinoma in situ)
2 secondary outcomes
iDFS
Time frame: 3 years
EFS
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neoadjuvant therapy: TCbHPy and Neoadjuvant therapy: TCbHP in people with Breast Cancer, run by The First Affiliated Hospital with Nanjing Medical University at 1 site 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 11 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 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 Jue Wang, Doctor (+86-18061695508, wangjue200011@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
tpCR rate (ypT0/is ypN0) (time frame: 1 month after surgery). 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 21 Feb 2023.