Neoadjuvant With Trastuzumab, Pyrotinib Plus Palbociclib and Fulvestrant in HER2-positive, ER-positive Breast Cancer

NCT05076695 | Unknown Phase 2

• 1 other identifier: SCHBCC-N032
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Estrogen Receptor-positive Breast Cancer; HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Immediately after the surgery,through study completion, an average of 1 year

Secondary Outcomes (2)

• changes of Ki67

  through study completion, an average of 1 year

• objective response rate (ORR)

  at the end of the combination treatment, up to 1 year

Study Arms (1)

TPPF group

EXPERIMENTAL

Patients will be treated with Trastuzumab, Pyrotinib, Palbociclib plus Fulvestrant(TPPF).

Drug: Palbociclib; Drug: trastuzumab; Drug: pyrotinib; Drug: fulvestrant

Interventions

Palbociclib DRUG

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)

TPPF group

trastuzumab DRUG

8 mg/kg loading dose IV, then 6 mg/kg IV, every 3 weeks for a total of 6 administrations.

TPPF group

pyrotinib DRUG

Pyrotinib 400mg, PO daily, continuously

TPPF group

fulvestrant DRUG

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.

TPPF group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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;

You may not qualify if:

• 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
• 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 with long QT syndrome or QTc \> 470 ms.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Hospital

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Interventions

palbociclib; Trastuzumab; pyrotinib; Fulvestrant

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• zhimin U Shao, professor

  Fudan University Shanghai Cancer Center Shanghai, China, 200032

  PRINCIPAL INVESTIGATOR

Central Study Contacts

zhimin U Shao, professor

CONTACT

08602164175590; zhimingshao@yahoo.com

Zhonghua U Wang, professor

CONTACT

08602164175590; zhonghuawang95@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Patients will enter the single-arm treatment group and they will receive a combination regimen (trastuzumab, pyrotinib, palbociclib plus Fulvestrant, TPPF) as neoadjuvant therapy.

Study Record Dates

• First Submitted: September 18, 2021
• First Posted: October 13, 2021
• Study Start: October 15, 2021
• Primary Completion: October 15, 2023
• Study Completion: October 15, 2024
• Last Updated: October 13, 2021

Record last verified: 2021-09

Locations

CN (1)