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Breast CancerPhase 3NCT04646759

Fulvestrant or Capecitabine Combined With Pyrotinib in HR+/HER2+ Metastatic Breast Cancer

A Phase 3 study testing Fulvestrant combined with Pyrotinib and Capecitabine combined with Pyrotinib in people with Breast Cancer, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Capecitabine combined with pyrotinib is the standard protocol for HR+/HER2+ advanced breast cancer after trastuzumab failure, but the incidence of grade 3 hand-foot-syndrome was 16.4%. Therefore, the search for efficient and low toxicity alternatives has become a research hotspot. Read more about this study

Who is it for?
Ages 18 to 80 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
Fulvestrant combined with Pyrotinib and Capecitabine combined with Pyrotinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
516 participants
Where
1 siteChina
Study dates
14 Oct 2020to 14 Dec 2030
Phase
Phase 3
Are there results?
Not yet: the study is under way

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 80 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult female patients (aged 18-80 years, including 18 and 80 years) with metastatic breast cancer confirmed by pathology or imaging are not suitable for surgical resection or radiotherapy for the purpose of cure;
  • Pathological examination confirmed that ER and / or PR were positive, and HER-2 was positive (ER expression: immunohistochemical staining of tumor cells ≥ 10%; PR expression: immunohistochemical staining of tumor cells ≥ 10%; HER-2 positive: immunohistochemical staining of 3 + or fish positive);
  • Postmenopausal patients (for premenopausal patients, ofs includes bilateral ovariectomy and GnRHa drugs);
  • The disease-free interval between the end of the last trastuzumab and tumor progression was more than 12 months;
  • Trastuzumab has not been treated or only received first-line treatment based on trastuzumab for metastatic diseases, and trastuzumab should be evaluated as effective in the rescue treatment of metastatic breast cancer for the first time.
  • Patients who have received chemotherapy and endocrine therapy in the past (New) adjuvant or for metastatic diseases, and have disease progression during or after treatment;
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  • The WHO physical status was 0-2 points, and the expected survival time was not less than 3 months;
  • At least one measurable lesion (short diameter of lymph node ≥ 15mm) was detected in the imaging examination within 2 weeks before enrollment, including normal CT scan ≥ 20 mm, spiral CT scan diameter ≥ 10 mm, or simple bone metastasis.
  • Previous treatment related toxicity should be reduced to NCI CTCAE (version 5.0) ≤ 1 degree (except for hair loss or other toxicity which is judged by the researcher to be safe for the patient)
  • Within one week before admission, blood routine examination was basically normal: A. white blood cell count (WBC) ≥ 3.0 × 10 ^ 9 / L; B. neutrophil count (ANC) ≥ 1.5 × 10 ^ 9 / L; C. platelet count (PLT) ≥ 100 × 10 ^ 9 / L;
  • Liver, kidney and heart function tests were basically normal within one week before enrollment (based on the normal values of laboratories in each research center): A. total bilirubin (TBIL) ≤ 1.5 × upper limit of normal value (ULN), B. alanine aminotransferase (ALT / AST) ≤ 2.5 × ULN (liver metastasis patients ≤ 5xuln), C. serum creatinine ≤ 1.5 × ULN or creatinine clearance rate (CCR) ≥ 60 ml / min; D. left ventricular ejection fraction (LVEF) ≥ 55%, e. QTcF(Fridericia correction) ≤ 470 ms.

Who cannot join

  • You cannot be grouped if you meet any of the following:
  • Patients who had not received trastuzumab, chemotherapy and endocrine therapy before;
  • Patients with central nervous system metastasis and clinical symptoms;
  • Patients with visceral crisis;
  • Patients who were considered suitable for chemotherapy by the researchers;
  • There are many factors that affect drug administration and absorption, such as dysphagia, chronic diarrhea and intestinal obstruction.
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  • Patients who received radiotherapy, chemotherapy, endocrine therapy, surgery (excluding local puncture) or molecular targeted therapy within 4 weeks before enrollment.
  • He participated in other clinical trials within 4 weeks before enrollment.
  • Patients with metastatic disease received more than first-line endocrine therapy, chemotherapy or targeted therapy.
  • Other malignant tumors in the past 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma or skin squamous cell carcinoma.
  • At the same time, they received any other anti-tumor treatment.
  • Those who have been known to have allergic history to the drug components of this regimen; have a history of immunodeficiency, including HIV positive, HCV, active hepatitis B, or other acquired and congenital immunodeficiency diseases, or have a history of organ transplantation.
  • Severe heart disease or discomfort, including, but not limited to, the following: a history of heart failure or systolic dysfunction (LVEF < 50%); high risk uncontrolled arrhythmias such as atrial tachycardia, resting heart rate > 100bpm, significant ventricular arrhythmias (such as ventricular tachycardia), or higher-level atrioventricular block (i.e., mobitz) The results showed that there was no significant difference between the two groups (systolic blood pressure > 180 mmHg and diastolic blood pressure > 100 mmHg);
  • Pregnant and lactating women, fertile women with positive baseline pregnancy test.
  • According to the judgment of the researchers, there are some accompanying diseases that seriously endanger the safety of patients or affect patients to complete the study.
  • Have a clear history of neurological or mental disorders, including epilepsy or dementia.
  • Any other situation in which the researcher believes that the patient is not suitable for the study, which may interfere with the accompanying diseases or conditions of the study, or have any serious medical obstacles that may affect the safety of the subjects (such as uncontrollable heart disease, hypertension, active or uncontrollable infection, active hepatitis B virus infection)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ying Wang contact

86-20-34070870

wangy556@mail.sysu.edu.cn

Jianli Zhao contact

86-20-34070499

zhaojli5@mail.sysu.edu.cn

China1 site, 1 recruiting

  • Sun Yat-sen Memorial Hospital, Sun Yat-sen University

    Guangzhou, Guangdong, 510000

    Ying Wang, 020-34070870, wangy556@mail.sysu.edu.cn

    Jianli Zhao, 020-34070499, zhaojli5@mail.sysu.edu.cn

    Recruiting

Other trials in China

About this study

Official title: Fulvestrant or Capecitabine Combined With Pyrotinib in HR-positive and HER2-Positive Metastatic Breast Cancer: A Multicenter, Randomized, Phase III Study

Capecitabine combined with pyrotinib is the standard protocol for HR+/HER2+ advanced breast cancer after trastuzumab failure, but the incidence of grade 3 hand-foot-syndrome was 16.4%. Therefore, the search for efficient and low toxicity alternatives has become a research hotspot. Our previous basic studies have shown that ER inhibitor fulvestrant and HER2 inhibitor pyrotinib have a synergistic effect. The preliminary analysis of our prospective shows that the efficacy is close to that of capecitabine combined with pyrotinib, and the adverse events are significantly improved compared with capecitabine combined with pyrotinib. Therefore, it is necessary to further carry out a head-to-head phase III randomized controlled clinical trial to study the efficacy and safety of fulvestrant combined with pyrotinib in the treatment of HR + / HER2 + advanced breast cancer.

Read the detailed description

Hormone receptor (HR) positive and human epidermal growth factor receptor-2 (HER-2) positive breast cancer has the characteristics of mild biological behavior and slow progression. Currently, capecitabine combined with pyrotinib is the standard protocol for this kind of advanced breast cancer after trastuzumab failure, and the median progression free survival (PFS) is 11.0 months. The incidence of grade 3 hand-foot-syndrome was 16.4%, the incidence of grade 3 diarrhea was 30.6%, and the incidence of grade 3 myelosuppression was 6%. Therefore, the search for efficient and low toxicity alternatives has become a research hotspot.

Our previous basic studies have shown that ER inhibitor fulvestrant and HER2 inhibitor pyrotinib have synergistic effect in inhibiting the proliferation of HR + / HER2 + breast cancer cells. At the same time, the preliminary analysis of our prospective, phase II, single arm study of "Fulvestrant combined with Pyrotinib in the treatment of HR + / HER2 + advanced breast cancer" shows that the efficacy is close to that of capecitabine combined with pyrotinib (median progression free survival is more than 13 months), and the adverse events are significantly improved compared with capecitabine combined with pyrotinib (grade 3 hand-foot-syndrome). This project has been supported by the "Sun-yat sun clinical research and cultivation project" of Sun-Yat Sen Memorial Hospital, Sun-Yat Sen University. Therefore, it is necessary to further carry out a head-to-head phase III randomized controlled clinical trial to study the efficacy and safety of fulvestrant combined with pyrotinib in the treatment of HR + / HER2 + advanced breast cancer, with a non-inferiority cut-off value of HR = 1.30. Combined with the analysis of biomarkers, to find the molecular indicators to predict the benefit of pyrotinib combined with endocrine therapy, so as to provide theoretical basis for guiding precise treatment.

Conditions
Breast Cancer
Being tested
Fulvestrant combined with Pyrotinib, Capecitabine combined with Pyrotinib
Keywords
HR-postitive/HER2-positive metastatic breast cancer, fulvestrant, Pyrotinib, capecitabine
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fulvestrant combined with PyrotinibDrug

    Also called FASLODEX combined with Pyrotinib

    Fulvestrant 500mg was injected intramuscularly on D1, D15, D28 and D28 Pyrotinib 400mg daily

  • Capecitabine combined with PyrotinibDrug

    Also called xeloda combined with Pyrotinib

    Capecitabine 1000mg/m^2 bid d1-d14，every 21 days Pyrotinib 400mg daily

Study groups in NCT04646759
Study groupRoleWhat they receive
Fulvestrant Combined With PyrotinibExperimentalFulvestrant, 500 mg, was injected intramuscularly on D1, D15, D28, D28, once every 28 days； Pyrotinib, 400mg, orally administered daily.
Receives: Drug: Fulvestrant combined with Pyrotinib
Capecitabine Combined With PyrotinibActive comparatorCapecitabine, 1000mg / m^2, twice daily; Pyrotinib, 400mg, orally administered daily.
Receives: Drug: Capecitabine combined with Pyrotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival

    The interval from the date of randomization to the first imaging confirmed progression of disease or death from any cause.

    Measured: 24 months

  2. Incidence of grade 3 hand foot syndrome (rate)

    From the date of enrollment to one year, the incidence of grade 3 hand-foot syndrome in the fulvestrant combined with pyrotinib group was compared with that of capecitabine combined with pyrotinib group. The incidence and severity of hand-foot syndrome were evaluated according to CTCAE 5.0 every 9 weeks (± 7 days).

    Measured: From the date of enrollment to one year

Secondary outcomes (6)

  1. Overall survival (OS)

    The time interval from the date of randomization to death due to any cause

    Measured: 50 months

  2. Objective response rate (ORR)

    According to recist1.1 standard, the proportion of patients whose best remission was CR or PR accounted for the total number of evaluable patients.

    Measured: 12 months

  3. Clinical Benefit Rate (CBR)

    According to recist1.1 standard, the proportion of patients whose best remission was CR or PR or SD ≥ 24 weeks accounted for the total number of evaluable patients.

    Measured: 12 months

  4. Biomarkers and treatment sensitivity analysis

    Cox univariate and multivariate analysis will be used to explore the correlation between endocrine and HER2 pathway related biomarkers and treatment sensitivity（The biomarkers to be analyzed included 324 tumor related genes included in the FoundationOne CDx, and ER/PR/HER2/ki67 in IHC）

    Measured: 12 months

  5. Quality of life score

    Quality of life data will be collected using the following questionnaires: FACT-B score

    Measured: 12 months

  6. Incidence of adverse events

    From the date of enrollment to one year, the incidence of adverse events in the fulvestrant combined with pyrotinib group was compared with that of capecitabine combined with pyrotinib group.

    Measured: from the date of enrollment to one year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2020
  2. Study start14 Oct 2020
  3. Primary completion14 Dec 2028 (estimated)
  4. Study completion14 Dec 2030 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Patients were randomly assigned to capecitabine plus pyrotinib or fulvestrant plus pyrotinib
Masking
None (open label)
Enrolment
516 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04646759
Sponsor's protocol ID
2020-KY-140
Status last verified
Nov 2020
First submitted
27 Oct 2020
Last updated
30 Nov 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Because the data involves the patient's personal information, it is temporarily decided that we will not disclose the individual participant data.

Publications

  • Ma F, Ouyang Q, Li W, Jiang Z, Tong Z, Liu Y, Li H, Yu S, Feng J, Wang S, Hu X, Zou J, Zhu X, Xu B. Pyrotinib or Lapatinib Combined With Capecitabine in HER2-Positive Metastatic Breast Cancer With Prior Taxanes, Anthracyclines, and/or Trastuzumab: A Randomized, Phase II Study. J Clin Oncol. 2019 Oct 10;37(29):2610-2619. doi: 10.1200/JCO.19.00108. Epub 2019 Aug 20.

    PubMed 31430226

  • Ma F, Li Q, Chen S, Zhu W, Fan Y, Wang J, Luo Y, Xing P, Lan B, Li M, Yi Z, Cai R, Yuan P, Zhang P, Li Q, Xu B. Phase I Study and Biomarker Analysis of Pyrotinib, a Novel Irreversible Pan-ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer. J Clin Oncol. 2017 Sep 20;35(27):3105-3112. doi: 10.1200/JCO.2016.69.6179. Epub 2017 May 12.

    PubMed 28498781

  • Chen Q, Ouyang D, Anwar M, Xie N, Wang S, Fan P, Qian L, Chen G, Zhou E, Guo L, Gu X, Ding B, Yang X, Liu L, Deng C, Xiao Z, Li J, Wang Y, Zeng S, Hu J, Zhou W, Qiu B, Wang Z, Weng J, Liu M, Li Y, Tang T, Wang J, Zhang H, Dai B, Tang W, Wu T, Xiao M, Li X, Liu H, Li L, Yi W, Ouyang Q. Effectiveness and Safety of Pyrotinib, and Association of Biomarker With Progression-Free Survival in Patients With HER2-Positive Metastatic Breast Cancer: A Real-World, Multicentre Analysis. Front Oncol. 2020 May 25;10:811. doi: 10.3389/fonc.2020.00811. eCollection 2020.

    PubMed 32528890

  • Lin Y, Lin M, Zhang J, Wang B, Tao Z, Du Y, Zhang S, Cao J, Wang L, Hu X. Real-World Data of Pyrotinib-Based Therapy in Metastatic HER2-Positive Breast Cancer: Promising Efficacy in Lapatinib-Treated Patients and in Brain Metastasis. Cancer Res Treat. 2020 Oct;52(4):1059-1066. doi: 10.4143/crt.2019.633. Epub 2020 Apr 24.

    PubMed 32340083

  • Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. doi: 10.1200/JCO.2017.74.7824. Epub 2017 Dec 15.

    PubMed 29244528

  • Robertson JFR, Steger GG, Neven P, Barni S, Gieseking F, Nole F, Pritchard KI, O'Malley FP, Simon SD, Kaufman B, Petruzelka L. Activity of fulvestrant in HER2-overexpressing advanced breast cancer. Ann Oncol. 2010 Jun;21(6):1246-1253. doi: 10.1093/annonc/mdp447. Epub 2009 Oct 29.

    PubMed 19875750

  • Tolaney SM, Wardley AM, Zambelli S, Hilton JF, Troso-Sandoval TA, Ricci F, Im SA, Kim SB, Johnston SR, Chan A, Goel S, Catron K, Chapman SC, Price GL, Yang Z, Gainford MC, Andre F. Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with hormone receptor-positive, HER2-positive advanced breast cancer (monarcHER): a randomised, open-label, phase 2 trial. Lancet Oncol. 2020 Jun;21(6):763-775. doi: 10.1016/S1470-2045(20)30112-1. Epub 2020 Apr 27.

    PubMed 32353342

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fulvestrant combined with Pyrotinib and Capecitabine combined with Pyrotinib in people with Breast Cancer, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen 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 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: looking for participants now, as of the sponsor's last update on 30 Nov 2020. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ying Wang (86-20-34070870, wangy556@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (time frame: 24 months). 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?

On the ClinicalTrials.gov record for NCT04646759, which also lists 7 linked publications.

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 30 Nov 2020.

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