Pyrotinib Combined With Trastuzumab and AI in the First-line Treatment of HER2 Positive/ HR Positive MBC

NCT ID: NCT03910712

Last Updated: 2019-04-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-01
• Study Completion Date: 2023-12-01

Brief Summary

This study is a randomized, open-label, phase II study, comparing the efficacy and safety of trastuzumab plus aromatase inhibitors, with or without pyrotinib, in the treatment of HR (hormone receptor)+/HER2 (human epidermal growth factor receptor 2) + MBC and inoperable LABC patients.

Detailed Description

This is a randomized, two-arm, open-label, multicenter phase II trial. Our primary purpose is to compare that PFS of patients with trastuzumab, AI plus pyrotinib and trastuzumab plus an AI for HER2-positive and hormone receptor-positive MBC or locally advanced breast cancer (LABC).

Eligible patients will randomized to a ratio of 1:1 to pyrotinib+ trastuzumab + aromatase inhibitor (experimental group) or trastuzumab+aromatase inhibitor (control group). Stratification factors were 1)time since adjuvant hormone therapy (<=12 months/>12 months/no prior hormone therapy); 2) lesion (visceral; non-visceral).

In treatment period, patients will be administrated trastuzumab plus aromatase inhibitors, with or without pyrotinib, every 21 days for 1 cycle, until disease progression, toxicity intolerance, withdrawal of informed consent, patients judged must be terminated study termination.

The imaging evaluation was performed according to the RECIST 1.1 criteria every 6 weeks.

Conditions

Breast Cancer Female; HER2-positive Breast Cancer; Hormone Receptor Positive Malignant Neoplasm of Breast; Metastatic Breast Cancer; Breast Diseases; Hormone Receptor Positive Tumor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pyrotinib and trastuzumab plus aromatase inhibitor

Participants will receive pyrotinib in combination with trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

Group Type: EXPERIMENTAL

Pyrotinib

Intervention Type: DRUG

Pyrotinib were administered 400 mg orally daily. Oral administration within 30 minutes after breakfast, and continuous administration for 21 days for 1 cycle.

Trastuzumab

Intervention Type: DRUG

Trastuzumab were administered every 3 weeks intravenously (8 mg/kg loading doses followed by 6 mg/kg maintenance doses).

Aromatase inhibitor

Intervention Type: DRUG

The investigator chose an aromatase inhibitor (either anastrozole, letrozole or exemestane 1 mg/2.5 mg/25 mg), once daily, oral.

Trastuzumab plus aromatase inhibitor

Participants will receive trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: DRUG

Trastuzumab were administered every 3 weeks intravenously (8 mg/kg loading doses followed by 6 mg/kg maintenance doses).

Aromatase inhibitor

Intervention Type: DRUG

The investigator chose an aromatase inhibitor (either anastrozole, letrozole or exemestane 1 mg/2.5 mg/25 mg), once daily, oral.

Interventions

Pyrotinib

Pyrotinib were administered 400 mg orally daily. Oral administration within 30 minutes after breakfast, and continuous administration for 21 days for 1 cycle.

Intervention Type: DRUG

Trastuzumab

Trastuzumab were administered every 3 weeks intravenously (8 mg/kg loading doses followed by 6 mg/kg maintenance doses).

Intervention Type: DRUG

Aromatase inhibitor

The investigator chose an aromatase inhibitor (either anastrozole, letrozole or exemestane 1 mg/2.5 mg/25 mg), once daily, oral.

Intervention Type: DRUG

Other Intervention Names

Study drug; Herceptin®; anastrozole, letrozole or exemestane

Eligibility Criteria

Inclusion Criteria

1. Age≥18 years, female;

2. Postmenopausal or pre-menopausal with ovarian function suppression;

3. At least one measurable lesion evaluable according to Response Evaluation Criteria In Solid Tumors Version 1.1;

4. Metastatic or inoperable local advanced breast cancer;

5. HER2-positive breast cancer;

6. HR-positive breast cancer;

7. LVEF ≥50%;

Exclusion Criteria

1. Previous systemic non-hormonal anticancer therapy in the metastatic or advanced breast cancer setting;

2. Received endocrine therapy within 7 days before randomization;

3. Uncontrolled central nervous system metastases;

4. Disease-free interval from completion of adjuvant/neo-adjuvant systemic non-hormonal treatment to recurrence of within 6 months.

5. Other malignancies within the last 3 years, except for carcinoma in situ of the cervix or basal cell carcinoma.

6. Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment

7. Severe organ dysfunction as assessed by signs and symptoms, laboratory studies and rapid progression of disease, which leading to a clinical indication for chemotherapy.

8. History of CHF of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal supraventricular tachycardia);

9. History of myocardial infarction within 6 months of randomization

10. History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy

11. Pregnant or lactating women;

12. QT interval>470 ms；

13. Serious concomitant diseases (including severe hypertension, severe diabetes, active infection, thyroid disease, etc.) that are harmful to the patient's safety or affect the patient's completion of the study;

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Qiang SUN

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Qiang Sun, M.D.

Role: STUDY_CHAIR

Peking Union Medical College Hospital

Central Contacts

Qiang Sun, M.D.

Role: CONTACT

sunqiangpumch@sina.com

86-10-69158721

Changjun Wang, M.D.

Role: CONTACT

wcj_sumy@126.com

86-10-69158721

References

Wang C, Lin Y, Zhou Y, Mao F, Zhu H, Guan J, Zhang X, Shen S, Huang X, Chen C, Yao R, Zhao J, Sun Q. Pyrotinib with trastuzumab and aromatase inhibitors as first-line treatment for HER2 positive and hormone receptor positive metastatic or locally advanced breast cancer: study protocol of a randomized controlled trial. BMC Cancer. 2020 Jul 13;20(1):653. doi: 10.1186/s12885-020-07143-2.

Reference Type: DERIVED

PMID: 32660609 (View on PubMed)

Other Identifiers

BREAST-Pyrotinib

Identifier Type: -

Identifier Source: org_study_id