Estrogen Receptor-positive Breast CancerPhase 2NeoTPPFNCT05076695
Neoadjuvant With Trastuzumab, Pyrotinib Plus Palbociclib and Fulvestrant in HER2-positive, ER-positive Breast Cancer
A Phase 2 study testing Palbociclib, trastuzumab and pyrotinib in people with Estrogen Receptor-positive Breast Cancer and HER2-positive Breast Cancer, run by Fudan University at 1 site in China.
Trial summary
This is a prospective Single-arm Study to Investigate the Efficacy and Safety of Neoadjuvant treatment with trastuzumab and pyrotinib plus palbociclib and fulvestrant in HER2-positive, ER-positive breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Estrogen Receptor-positive Breast Cancer, HER2-positive Breast Cancer
- What is being tested?
- Palbociclib, trastuzumab and pyrotinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteChina
- Study dates
- 15 Oct 2021to 15 Oct 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age: 18 or older than 18;
- Postmenopausal; Pre-menopausal and peri-menopausal female patients must receive ovarian function inhibitors or ovariectomy concurrently.
- Have not received chemotherapy or endocrine therapy in the past;
- Have been confirmed as breast invasive ductal carcinoma by the imaging examination and pathological biopsy;
- Patients with locally advanced breast cancer, stage IIa-IIIa
- HER2 status to be centrally confirmed (HER2 3+ of neu amplified)
Show all 19Show fewer
- Positive estrogen receptor (ER) > 10%
- Estimated survival > 12 months;
- ECOG physical status score before treatment is 0-1 points;
- The patient has a measurable lesion (according to the standard RECIST 1.1);
- Willing to cooperate with pre-treatment needle biopsy and neoadjuvant therapy;
- No serious metastasis, no brain metastasis, no liver metastasis;
- Normal bone marrow function, blood neutrophils ≥ 1.5x109 / L, hemoglobin ≥ 100g / L, platelets ≥ 100x109 / L;
- normal liver and kidney function, blood AST≤60U/L, total bilirubin ≤2.5 times of the normal upper limit, and serum creatinine ≤110µmol/L, urea nitrogen ≤7.1mmol/L;
- No abnormal blood coagulation;
- Normal heart function, normal ECG and LVEF ≥ 55%;
- Women of childbearing age are willing to take reliable contraceptive measures during clinical trials, and the serum or urine pregnancy test is negative within 7 days before administration; no coagulation abnormality;
- Sign the informed consent form (ICF) and voluntarily receive follow-up visits, treatment, laboratory tests and other study procedures as planned.
- -
Who cannot join
- Have performed any local or systemic treatment (including chemotherapy, radiotherapy, targeted drug therapy, experimental treatment, etc.) for the breast cancer;
- Inflammatory breast cancer, bilateral breast cancer or breast cancer with distant metastasis found;
- Subjects with uncontrolled lung disease, severe infection, active gastrointestinal ulcer, coagulopathy, severe uncontrolled diabetes, connective tissue disease or inhibition of bone marrow function who cannot tolerate neoadjuvant therapy and related therapy;
- Peripheral neuropathy caused by any factor > 1 degree;
- Subjects who previously have a history of congestive heart failure, uncontrolled or symptomatic angina, arrhythmia or myocardial infarction, and uncontrollable hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg);
- Previous extensive radiotherapy
Show all 19Show fewer
- Current use or anticipated need for food or drugs that are known strong CYP3A4 (cytochrome P450 3A4) inhibitors or inducers.
- Strong CYP3A inhibitors, including, boceprevir, clarithromycin, conivaptan, delavirdine, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, suboxone, telaprevir, telithromycin, voriconazole, and grapefruit, grapefruit juice or any product containing grapefruit.
- Strong CYP3A inducers, including carbamazepine, phenytoin, primidone, rifampin, rifapentin, and St. John's wort.
- Breast cancer during the lactation period and gestation period;
- Reluctance to receive pre-treatment biopsy and neoadjuvant therapy;
- Psychiatric patients or other factors that cause non-compliance with the treatment;
- Subjects who are known to have a history of severe allergies to any drug in the treatment regimen; patients who have undergone major surgery or severe trauma within 2 months prior to the first administration; subjects who currently or recently (within 30 days prior to enrolment) have used another investigational drug or participated in another study;
- Subjects who are known to have infected with human immunodeficiency virus (HIV);
- Subjects who have other conditions unsuitable for inclusion as considered by investigators, combined with CYP3A4 inhibitors or inducers;
- Subjects with long QT syndrome or QTc > 470 ms.
- According to the judgement of the researchers, there are concomitant diseases that seriously endanger the safety of patients or affect the completion of research (including, but not limited to, severe hypertension, severe diabetes, active infections, etc.).
- Moderate infection occurs within 4 weeks before the first administration (e.g. intravenous drip of antibiotics, antifungal or antiviral drugs according to clinical criteria), fever of unknown origin occurs during the screening period/before the first administration.
- -
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Hospital
Shanghai, Shanghai Municipality, 200032
Zhimin Shao, M.D., +86-021-64175590 ext. 88807, zhimingshao@yahoo.com
Yin U Liu, M.D, +86-021-64175590 ext. 88603, liuyinfudan@163.com
About this study
This is a prospective Single-arm Study to Investigate the Efficacy and Safety of Neoadjuvant treatment with trastuzumab and pyrotinib plus palbociclib and fulvestrant in HER2-positive, ER-positive breast cancer.
Read the detailed description
ER+HER2+ breast cancer have low response to single endocrine therapy, however the efficacy was improved when treated with endocrine therapy combined with anti-HER2 target therapy. Palbociclib, to be a CDK4/6 inhibitor, has synergistic with tamoxifen and trastuzumab in ER+/HER2+ cells. In China, there is nearly 40000 new patients with ER+/HER2+ breast cancer every year. The encouraging results in NA-PHER2 study suggested the triple targeting of ER, HER2, and RB1 could be an effective chemotherapy-free treatment strategy in neoadjuvant therapy. However, pertuzumab is very expensive. The investigators plan to replace pertuzumab with pyrotinib. Pyrotinib, a new irreversible pan-Her inhibitor in China pharmaceutical company. The objective is to evaluate the efficacy and safety of Neoadjuvant treatment with trastuzumab and pyrotinib plus palbociclib and fulvestrant (TPPF) in this target population. 37 patients will enter the single-arm treatment group. The participants will receive an association of drugs (trastuzumab, pyrotinib, palbociclib plus Fulvestrant, TPPF) as neoadjuvant therapy. Surgery will be performed not earlier than 14 days and not later than 28 days after the last dose of any of the drugs in the combination. The primary endpoint is the rate of pathological complete response (pCR) defined as ypT0-ypTis ypN0 at surgery. The secondary endpoint include the change in Ki67 expression from baseline and at C2D15 of treatment and at surgery, objective response rate and safety.
- Being tested
- Palbociclib, trastuzumab, pyrotinib, fulvestrant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PalbociclibDrug
Palbociclib will be given at the dose of 125 mg po q.d. x 21 every 4 weeks (i.e. 1 week rest period for a total of 5 cycles)
trastuzumabDrug
8 mg/kg loading dose IV, then 6 mg/kg IV, every 3 weeks for a total of 6 administrations.
pyrotinibDrug
Pyrotinib 400mg, PO daily, continuously
fulvestrantDrug
Fulvestrant will be administered according to local prescription guidelines and will be given intramuscle at the dose of 500 mg every 4 weeks (repeat for 5 times) with an additional 500 mg dose given two weeks after the initial dose.
| Study group | Role | What they receive |
|---|---|---|
| TPPF group | Experimental | Patients will be treated with Trastuzumab, Pyrotinib, Palbociclib plus Fulvestrant(TPPF). Receives: Drug: Palbociclib; Drug: trastuzumab; Drug: pyrotinib; Drug: fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathological complete response (pCR)
Defined as the absence of any invasive cancer cells in the resected breast specimen and all resected lymph nodes following the completion of neoadjuvant therapy. If there is only carcinoma in situ remains, it can be regarded as pCR.
Measured: Immediately after the surgery,through study completion, an average of 1 year
Secondary outcomes (2)
changes of Ki67
changes of Ki67 from baseline and at cycle2/day 15 and at surgery (approximately 22 weeks after start of neoadjuvant therapy.
Measured: through study completion, an average of 1 year
objective response rate (ORR)
The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)
Measured: at the end of the combination treatment, up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2021
- Study start15 Oct 2021 (estimated)
- Primary completion15 Oct 2023 (estimated)
- Study completion15 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Estrogen Receptor-positive Breast CancerStudies of the same condition, open and under way.
- More trials run by Fudan 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
- Not applicable
- Intervention model
- Single group
- Model description
- Patients will enter the single-arm treatment group and they will receive a combination regimen (trastuzumab, pyrotinib, palbociclib plus Fulvestrant, TPPF) as neoadjuvant therapy.
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhimin Shao, Fudan University
- Investigators
- zhimin U Shao, professor, Principal investigator, Fudan University Shanghai Cancer Center Shanghai, China, 200032
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05076695
- Sponsor's protocol ID
- SCHBCC-N032
- Acronym
- NeoTPPF
- Status last verified
- Sep 2021
- First submitted
- 18 Sep 2021
- Last updated
- 13 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant With Trastuzumab, Pyrotinib Plus Palbociclib and Fulvestrant in HER2-positive, ER-positive Breast Cancer
- ClinicalTrials.gov ID
- NCT05076695
- Acronym / sponsor ID
- NeoTPPF / SCHBCC-N032
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 15 Oct 2021 (estimated)
- Primary completion
- 15 Oct 2023 (estimated)
- Study completion
- 15 Oct 2024 (estimated)
- First posted
- 13 Oct 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 Single-arm Study to Investigate the Efficacy and Safety of Neoadjuvant treatment with trastuzumab and pyrotinib plus palbociclib and fulvestrant in HER2-positive, ER-positive breast cancer.
Detailed description
ER+HER2+ breast cancer have low response to single endocrine therapy, however the efficacy was improved when treated with endocrine therapy combined with anti-HER2 target therapy. Palbociclib, to be a CDK4/6 inhibitor, has synergistic with tamoxifen and trastuzumab in ER+/HER2+ cells. In China, there is nearly 40000 new patients with ER+/HER2+ breast cancer every year. The encouraging results in NA-PHER2 study suggested the triple targeting of ER, HER2, and RB1 could be an effective chemotherapy-free treatment strategy in neoadjuvant therapy. However, pertuzumab is very expensive. The investigators plan to replace pertuzumab with pyrotinib. Pyrotinib, a new irreversible pan-Her inhibitor in China pharmaceutical company. The objective is to evaluate the efficacy and safety of Neoadjuvant treatment with trastuzumab and pyrotinib plus palbociclib and fulvestrant (TPPF) in this target population. 37 patients will enter the single-arm treatment group. The participants will receive an association of drugs (trastuzumab, pyrotinib, palbociclib plus Fulvestrant, TPPF) as neoadjuvant therapy. Surgery will be performed not earlier than 14 days and not later than 28 days after the last dose of any of the drugs in the combination. The primary endpoint is the rate of pathological complete response (pCR) defined as ypT0-ypTis ypN0 at surgery. The secondary endpoint include the change in Ki67 expression from baseline and at C2D15 of treatment and at surgery, objective response rate and safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients will enter the single-arm treatment group and they will receive a combination regimen (trastuzumab, pyrotinib, palbociclib plus Fulvestrant, TPPF) as neoadjuvant therapy.
| Arm | Type | Receives |
|---|---|---|
| TPPF group | Experimental | Drug: Palbociclib, Drug: trastuzumab, Drug: pyrotinib, Drug: fulvestrantPatients will be treated with Trastuzumab, Pyrotinib, Palbociclib plus Fulvestrant(TPPF). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Age: 18 or older than 18;
- Postmenopausal; Pre-menopausal and peri-menopausal female patients must receive ovarian function inhibitors or ovariectomy concurrently.
- Have not received chemotherapy or endocrine therapy in the past;
- Have been confirmed as breast invasive ductal carcinoma by the imaging examination and pathological biopsy;
- Patients with locally advanced breast cancer, stage IIa-IIIa
Key exclusion criteria (19 listed)
- Have performed any local or systemic treatment (including chemotherapy, radiotherapy, targeted drug therapy, experimental treatment, etc.) for the breast cancer;
- Inflammatory breast cancer, bilateral breast cancer or breast cancer with distant metastasis found;
- Subjects with uncontrolled lung disease, severe infection, active gastrointestinal ulcer, coagulopathy, severe uncontrolled diabetes, connective tissue disease or inhibition of bone marrow function who cannot tolerate neoadjuvant therapy and related therapy;
- Peripheral neuropathy caused by any factor > 1 degree;
- Subjects who previously have a history of congestive heart failure, uncontrolled or symptomatic angina, arrhythmia or myocardial infarction, and uncontrollable hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg);
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 |
|---|---|---|
| PalbociclibPalbociclib will be given at the dose of 125 mg po q.d. x 21 every 4 weeks (i.e. 1 week rest period for a total of 5 cycles) | Drug | TPPF group |
| trastuzumab8 mg/kg loading dose IV, then 6 mg/kg IV, every 3 weeks for a total of 6 administrations. | Drug | TPPF group |
| pyrotinibPyrotinib 400mg, PO daily, continuously | Drug | TPPF group |
| fulvestrantFulvestrant will be administered according to local prescription guidelines and will be given intramuscle at the dose of 500 mg every 4 weeks (repeat for 5 times) with an additional 500 mg dose given two weeks after the initial dose. | Drug | TPPF group |
Primary outcome
pathological complete response (pCR)
Time frame: Immediately after the surgery,through study completion, an average of 1 year
Defined as the absence of any invasive cancer cells in the resected breast specimen and all resected lymph nodes following the completion of neoadjuvant therapy. If there is only carcinoma in situ remains, it can be regarded as pCR.
2 secondary outcomes
changes of Ki67
Time frame: through study completion, an average of 1 year
objective response rate (ORR)
Time frame: at the end of the combination treatment, up to 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2021.
Related trials for Estrogen Receptor-positive Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Recruiting
Short-Term Reduced Dietary Protein in ER+/HER2- Breast Cancer Patients During Neoadjuvant Chemotherapy
Breast Cancer, Hormone Receptor Positive / HER2-negative Breast Cancer
Active, not recruitingObservational study
Longitudinal ctDNA Surveillance for Older Women With ER+ Breast Cancer Who Omit Surgery
Breast Cancer
Not yet recruiting
Prospective Study to Evaluate the Clinical Utility of ctDNA Tumor Fraction (TF) for Detection of Estrogen Receptor 1 (ESR1) Mutations in (Human Epidermal Growth Factor Receptor) HR+/HER2- Metastatic Breast Cancer (MBC)
Breast Cancer, Metastatic Breast Cancer
Recruiting
Signatera-Guided CDK4/6 Inhibitor Therapy in Breast Cancer
Breast Neoplasms, Carcinoma, Ductal, Breast
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.
zhimin U Shao, professor principal investigator
Fudan University Shanghai Cancer Center Shanghai, China, 200032
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 Palbociclib, trastuzumab and pyrotinib in people with Estrogen Receptor-positive Breast Cancer and HER2-positive Breast Cancer, run by Fudan 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 19 inclusion and 19 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 13 Oct 2021. 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 zhimin U Shao, professor (08602164175590 ext. 88807, zhimingshao@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pathological complete response (pCR) (time frame: Immediately after the surgery,through study completion, an average of 1 year). 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 13 Oct 2021.