Clinical trial NCT03910712: Pyrotinib Combined With Trastuzumab and AI in the First-line Treatment of HER2 Positive/ HR Positive MBC
Official title: A Randomized, Open-label Study of First Line Pyrotinib, Trastuzumab With an Aromatase Inhibitors, in the Treatment of HER2 Positive and HR Positive Metastatic or Inoperable Locally Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer Female
HER2-positive Breast Cancer
Hormone Receptor Positive Malignant Neoplasm of Breast
Metastatic Breast Cancer
Breast Diseases
Hormone Receptor Positive Tumor
Keywords: MBC, Pyrotinib, Trastuzumab, First line, HER2
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2019-04-10
Enrollment: 250
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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;

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From randomization to 36 month
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization to 36 month
measure: Objective Overall Response Rate (ORR)
timeFrame: From randomization to 36 month
measure: Duration of Response (DoR)
timeFrame: From randomization to 36 month
measure: Time to Response (TTR)
timeFrame: From randomization to 36 month
measure: Clinical Benefit Response (CBR)
timeFrame: From randomization to 36 month
measure: Adverse events (AEs)
timeFrame: From screening phase until AEs returns to Grade 0-1 or baseline
measure: Quality of Life (QoL) by FACT-B
timeFrame: From randomization to 36 month
measure: Quality of Life (QoL) by EQ-5D
timeFrame: From randomization to 36 month
Other outcomes:
Locations:
Study officials:
affiliation: Peking Union Medical College Hospital
name: Qiang Sun, M.D.
role: STUDY_CHAIR
References:
citation: 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.