AzTrials
AzTrials

Breast CancerPhase 1/2PLEASURABLENCT03772353

Pyrotinib, Dalpiciclib(SHR6390) and Endocrine Therapy in Subjects With Dual-receptor Positive(ER+/HER2+) Advanced Breast Cancer

A Phase 1/2 study testing Dalpiciclib, Pyrotinib and Letrozole in people with Breast Cancer, run by Fudan University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

This is a single-center Ib / II study of triple targeted drug combination (endocrine therapy，novel HER2-targeted small molecule inhibitor pyrotinib and CDK4/6 inhibitor dalpiciclib(SHR6390) ) as a first or second line of therapy in patients with relapsed/metastatic hormone receptor positive and HER2-positive breast… Read more about this study

Who is it for?
Ages 18 to 75 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
Dalpiciclib, Pyrotinib and Letrozole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
1 siteChina
Study dates
12 May 2019to 10 Dec 2025
Phase
Phase 1/2
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

  • Subjects voluntarily joined the study, signed informed consent, and had good compliance.
  • Postmenopausal or premenopausal perimenopausal female patients aged ≥ 18 years and ≤ 75 years old,Meet one of the following:
  • Previous bilateral oophorectomy, or age ≥ 60 years; or Age <60, natural postmenopausal state (defined as regular months for at least 12 consecutive months After spontaneous cessation and no other pathological or physiological reasons),E2 and FSH in menopause Post-level; or
  • Pre-menopausal or perimenopausal female patients can also be included, but must be willing to receive treatment with LHRH agonists;
  • Patients with HR+/HER2+ recurrent or metastatic breast cancer confirmed by histopathology
  • HER2 positivity is defined by standard of 3+ staining by immunohistochemical staining (IHC) or positive for in situ hybridization (ISH)
Show all 27Show fewer
  • Estrogen receptor(ER) or Progesterone receptor(PR) positive is defined as the percentage of cells positive for ER or PR expression ≥ 1%
  • Local recurrence needs to be confirmed by the physician that is unresectable
  • At least one extracranial measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.
  • Prior treatment:
  • Previously received no more than 1 prior lines of systemic treatment with trastuzumab regimen for repetitive metastatic diabetes [including anti-HER2 ADC, subsequent meaning is the same]
  • The early stage includes trastuzumab-containing regimen treatment， or trastuzumab-containing regimen that relapses more than 1 year after the end of adjuvant treatment, and subsequent treatment is included as the first-line anti-HER2 treatment;
  • The first-line treatment fails with the trastuzumab-containing regimen, or the trastuzumab-containing regimen recurs during the adjuvant treatment or relapses within 1 year after the adjuvant treatment ends, the follow-up treatment will be included as the second-line anti-HER2 treatment;
  • Have not received anti-HER2 TKI treatment before or received but did not prove that the treatment failed;
  • Past endocrine therapy has not proven resistance to aromatase inhibitors (definition of resistance: recurrence during or within 1 year after treatment with adjuvant aromatase inhibitors, received aromatase inhibitors in the recurrence and metastasis stage and disease progression), follow-up Letrozole is selected for endocrine therapy. Past endocrine therapy has aromatase inhibitor resistance, and follow-up endocrine therapy is fulvestrant.
  • Eastern Cooperative Oncology Group Performance Status of 0-1.
  • Life expectancy ≥ 12 weeks.
  • Adequate function of major organs meets the following requirements (no blood components and cell growth factors have been used within 14 days before randomization):
  • Neutrophils ≥ 1.5×10^9/L
  • Platelets ≥ 90×10^9/L
  • Hemoglobin ≥ 90g/L
  • Total bilirubin≤ 1.5 × the upper limit of normal (ULN)
  • ALT and AST ≤ 2.5 × ULN
  • BUN and Cr ≤ 1.5 × ULN
  • Left ventricular ejection fraction (LVEF) ≥ 50%
  • QTcF(Fridericia correction) ≤ 470 ms
  • International normalized ratio(INR)≤1.5 × ULN，activated partial thromboplastin time(APTT) ≤ 1.5 × ULN

Who cannot join

  • Meningeal metastasis or active brain parenchymal metastasis. Patients with clinically stable brain parenchymal metastases can be included, including asymptomatic brain metastases that have not received local treatment; or patients who have previously received central nervous system metastasis therapy (radiotherapy or surgery), if imaging confirms that stability has been maintained for at least 4 weeks , and have stopped symptomatic treatment (including hormones and mannitol, etc.) for more than 2 weeks
  • Previously received any CDK4/6 inhibitor treatment.
  • There are ascites, pleural effusion, pericardial effusion with clinical symptoms at baseline, those who need drainage, or those who have undergone drainage of serous effusion within 4 weeks before the first dose.
  • Inability to swallow, intestinal obstruction or other factors affecting the administration and absorption of the drug.
  • Received systemic therapy such as chemotherapy, molecular targeted therapy or other clinical trial drugs within 4 weeks before enrollment; received endocrine therapy within 2 weeks before enrollment.
  • Patients with other malignant tumors within 5 years or at the same time( except for cured skin basal cell carcinoma and cervical carcinoma in situ).
Show all 17Show fewer
  • Have undergone major surgical procedures or significant trauma within 4 weeks prior to randomization, or are expected to undergo major surgery.
  • Pregnant women, lactating female, or women of childbearing age who are unwilling to take effective contraceptive measures.
  • Have a history of allergies to the drug components of this regimen.
  • Patients with active HBV and HCV infection; stable hepatitis B after drug treatment (HBV virus copy number is higher than the upper limit of reference value) and cured hepatitis C patients (HCV virus copy number exceeds the lower limit of detection method).
  • History of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, history of organ transplantation.
  • History of cardiac dysfunction, include(1)angina (2)clinical significant arrythmia or require drug intervention (3)myocardial infarction (4)heart failure (5) other cardiac dysfunction (judged by the physician); any cardiac or nephric abnormal ≥ grade 2 found in screening.
  • Female patients who are pregnancy, lactation or women who are of childbearing potential tested positive in baseline pregnancy test.
  • Childbearing female who refuse to accept any contraception practice.
  • Determined by the physician, any serious coexisting disease might be harmful to the patient's safety or avoid the patients from accomplishing the treatment(e.g serious hypertension, diabetes, thyroid dysfunction,active infection etc.).
  • History of neurological or psychiatric disorders, including epilepsy or dementia.
  • Severe infections within 4 weeks prior to first dose (eg, intravenous infusion of antibiotics, antifungal or antiviral drugs according to clinical protocols), or unexplained fever (T > 38.3 °C ) during screening or prior to first administration.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Fudan University Shanghai Cancer Center

    Shanghai, 200032

Other trials in China

About this study

Official title: Pyrotinib, Dalpiciclib(SHR6390) and Endocrine Therapy in Subjects With Dual-receptor Positive(ER+/HER2+) Advanced Breast Cancer: a Multi-center Phase Ib/II Study

This is a single-center Ib / II study of triple targeted drug combination (endocrine therapy，novel HER2-targeted small molecule inhibitor pyrotinib and CDK4/6 inhibitor dalpiciclib(SHR6390) ) as a first or second line of therapy in patients with relapsed/metastatic hormone receptor positive and HER2-positive breast cancer.

Read the detailed description

This is a single-center, single arm, open-label, run-in phase Ib / roll-over phase II study of endocrine therapy in combination with novel human epidermal growth factor receptor-2(HER2)-targeted tyrosine kinase Inhibitor pyrotinib and cyclin-dependent kinase 4/6(CDK4/6) Inhibitor dalpiciclib(SHR6390) in subjects with hormone receptor(HR)+/HER2+ relapsed or metastatic breast cancer. The study will enroll natural postmenopausal women, or women who have undergone bilateral oophorectomy.The phase Ib part of the study will determine safety and tolerability of the combination of endocrine therapy, pyrotinib and dalpiciclib to define that appropriate dose of dalpiciclib for phase II.Data from phase Ib showed the triplet of pyrotinib, dalpiciclib, andendocrine therapy had an acceptable safety profile and encouraging efficacy, potentially offering a chemotherapy-sparing treatment option for patients with HER2-positive/HR-positive MBC.Once the recommended regimen has been identified, subjects with the selected tumor type will be enrolled into expansion cohorts for the purpose of assessing efficacy and safety of the combination treatment.

Conditions
Breast Cancer
Being tested
Dalpiciclib, Pyrotinib, Letrozole, Fulvestrant
Keywords
hormone receptor, HER2, pyrotinib, CDK4/6 inhibitor
Medical subject headings
Breast Neoplasms

What participants receive

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

  • DalpiciclibDrug

    Also called SHR6390

    Dalpiciclib (SHR6390) is a novel small molecule inhibitor specifically targeting the CDK4/6 pathway.

  • PyrotinibDrug

    Pyrotinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising anti-tumour activity and acceptable tolerability in patients with HER2+ metastatic breast cancer (MBC)

  • LetrozoleDrug

    Letrozole, a third-generation aromatase inhibitor, is the principal drug used in the treatment of postmenopausal patients with both early- and advanced-stage endocrine-responsive breast cancer (BC).

  • FulvestrantDrug

    Fulvestrant is a selective oestrogen receptor (ER) degrader used in postmenopausal women with hormone receptor-positive advanced breast cancer

Study groups in NCT03772353
Study groupRoleWhat they receive
Dalpiciclib combined with Pyrotinib and Endocrine therapyExperimentalData from phase Ib showed the triplet of pyrotinib, SHR6390, and letrozole had an acceptable safety profile and encouraging efficacy, potentially offering a chemotherapy-sparing treatment option for patients with HER2-positive/HR-positive MBC. Based on DLTs and clinical efficacy, pyrotinib 320mg/d, SHR6390 125mg/d, and letrozole 2.5mg/d was declared as RP2D. The pharmacokinetic analysis had not yielded conclusive results and would involve more samples in phase II trial. Dalpiciclib combined with Pyrotinib and Endocrine therapy (treatment of physician's choice: letrozole or fulvestrant) ER+/HER2+ metastatic breast cancer patients eligible for first- or second-line treatment were enrolled to receive dalpiciclib combined with pyrotinib and endocrine therapy (treatment of physician's choice: letrozole or fulvestrant)
Receives: Drug: Dalpiciclib; Drug: Pyrotinib; Drug: Letrozole; Drug: Fulvestrant

What is being measured

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

  1. The number of patients in the Phase 1b part of the study with any adverse events (AE).

    To measure safety and tolerability of SHR6390 used in combination with and letrozole and pyrotinib (phase Ib part) we will assess the incidence, nature and severity of all adverse events (AE) that occur on or after C1D1 of therapy, AE severities will be classified using the CTCAE criteria.

    Measured: 2 years

  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

Timeline

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

  1. First posted11 Dec 2018
  2. Study start12 May 2019
  3. Primary completion10 Jun 2023 (estimated)
  4. Study completion10 Dec 2025 (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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03772353
Sponsor's protocol ID
PLEASURABLE
Acronym
PLEASURABLE
Status last verified
Mar 2023
First submitted
10 Dec 2018
Last updated
7 Mar 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Zhang J, Meng Y, Wang B, Wu X, Zheng H, Hu J, Liu W, Chen W, Wang L, Cao J, Tao Z, Li T, Ni S, Yu Z, Sun L, Wang Y, Peng Q, Wang S, Hu X, Wang J, Wu Y, Hu X. Dalpiciclib combined with pyrotinib and endocrine therapy in women with ER-positive, HER2-positive advanced breast cancer: A prospective, multicenter, single-arm, phase 2 trial. PLoS Med. 2025 Jul 31;22(7):e1004669. doi: 10.1371/journal.pmed.1004669. eCollection 2025 Jul.

    PubMed 40743286

  • Zhang J, Meng Y, Wang B, Wang L, Cao J, Tao Z, Li T, Yao W, Hu X. Dalpiciclib Combined With Pyrotinib and Letrozole in Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer (LORDSHIPS): A Phase Ib Study. Front Oncol. 2022 Mar 7;12:775081. doi: 10.3389/fonc.2022.775081. eCollection 2022.

    PubMed 35321427

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dalpiciclib, Pyrotinib and Letrozole in people with 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 27 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: status not confirmed, as of the sponsor's last update on 7 Mar 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The number of patients in the Phase 1b part of the study with any adverse events (AE). (time frame: 2 years). 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 NCT03772353, which also lists 2 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 7 Mar 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in