Pyrotinib Combined With Trastuzumab Plus Aromatase Inhibitor in Treatment of Breast Cancer

Pyrotinib Maleate Combined With Trastuzumab Plus Aromatase Inhibitor in the First-line Treatment of Advanced HER2-positive/HR-positive Breast Cancer Phase II Study

This study is a single-arm, open-label, phase II study, comparing the efficacy and safety of pyrotinib plus trastuzumab and aromatase inhibitors, in the treatment of HR (hormone receptor)+/HER2 (human epidermal growth factor receptor 2) + MBC and inoperable LABC patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Diseases; Metastatic Breast Cancer; HER2-positive Breast Cancer; Hormone Receptor Positive Malignant Neoplasm of Breast; Breast Cancer Female; Hormone Receptor Positive Tumor
• Intervention / Treatment: Drug: Pyrotinib; Drug: Trastuzumab; Drug: Aromatase Inhibitors

Detailed Description

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

In treatment period, patients will be administrated pyrotinib plus trastuzumab and aromatase inhibitors, 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.

• Study Type: Interventional
• Enrollment (Anticipated): 77
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chen Xi, PhD; Phone Number: 13705045925 13705045925; Email: cxifuzhou@163.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 365000
      • Fuzhou General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Age≥18 years,≤70 years, female;
2. Postmenopausal or pre-menopausal with ovarian function suppression;
3. with or without measurable lesion evaluable according to Response Evaluation Criteria In Solid Tumors Version 1.1;
4. Metastatic or inoperable local advanced Invasive breast cancer;
5. HER2-positive breast cancer;
6. HR-positive breast cancer;
7. LVEF ≥55%;QT interva<470 ms;
8. Eastern Cooperative Oncology Group(ECOG) scale 0-1;
9. Life expectancy ≥3 months;

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;Uncontrolled central nervous system metastases;
3. Disease-free interval from completion of adjuvant/neo-adjuvant systemic non-hormonal treatment to recurrence of within 6 months.
4. Other malignancies within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma.
5. 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
6. Severe organ dysfunction as assessed by signs and symptoms, laboratory studies and rapid progression of disease, which leading to a clinical indication for chemotherapy.
7. History of CHF of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal supraventricular tachycardia);
8. History of myocardial infarction within 6 months of randomization;
9. History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy;
10. Pregnant or lactating women;
11. QT interval>470 ms;
12. 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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Pyrotinib and trastuzumab plus aromatase inhibito; 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.

Drug: Pyrotinib; Pyrotinib were administered 400 mg orally daily. Oral administration within 30 minutes after breakfast, and continuous administration for 21 days for 1 cycle.; Other Names: Study drug; Drug: Trastuzumab; Trastuzumab were administered every 3 weeks intravenously (8 mg/kg loading doses followed by 6 mg/kg maintenance doses).; Other Names: Herceptin®; Drug: Aromatase Inhibitors; The investigator chose an aromatase inhibitor (either anastrozole, letrozole or exemestane 1 mg/2.5 mg/25 mg), once daily, oral.; Other Names: anastrozole, letrozole or exemestane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS was defined as the time from randomization to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or death from any cause, whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. The PFS will be will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median PFS, hazard ratio with appropriate confidence intervals will be reported.	From randomization to 36 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Overall Response Rate (ORR)	ORR was defined as percentage of participants with best (confirmed) overall response (BOR) of either CR or PR. ORR was assessed by the investigator according to RECIST version 1.1 and is based on BOR, which is defined as best response recorded from start of study treatment until disease progression/recurrence or death. Participants needed to have two consecutive assessments of PR or CR to be a responder. Only participants with measurable disease at baseline were included in the analysis of BOR and who did not have any evaluable post-baseline assessments were classified as not evaluable. The ORR will be reported by percentage with each arms and appropriate confidence intervals.	From randomization to 36 month
Duration of Response (DoR)	DoR is defined as date of initial confirmed PR/CR until date of progressive disease or death from any cause. PR or CR or SD is according to RECIST version 1.1. The DoR will be estimated using Kaplan-Meier method. Kaplan-Meier curves, median DoR, hazard ratio with appropriate confidence intervals will be reported.	From randomization to 36 month
Overall Survival (OS)	Overall Survival (OS), defined as the time from the date of randomization to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication and participants with no post-baseline information were censored at the date of randomization. The OS will be will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median OS, hazard ratio with appropriate confidence intervals will be reported.	From randomization to 36 month

Collaborators and Investigators

• Sponsor: Fuzhou General Hospital
• Investigators: Study Chair: Chen Xi, PhD, Fuzhou General Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 1, 2019
• Primary Completion (ANTICIPATED): November 1, 2021
• Study Completion (ANTICIPATED): November 1, 2023

Study Registration Dates

• First Submitted: September 11, 2019
• First Submitted That Met QC Criteria: September 11, 2019
• First Posted (ACTUAL): September 12, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 12, 2019
• Last Update Submitted That Met QC Criteria: September 11, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Site; Neoplasms; Breast Neoplasms; Breast Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Hormone Antagonists; Steroid Synthesis Inhibitors; Estrogen Antagonists; Trastuzumab; Letrozole; Anastrozole; Exemestane; Aromatase Inhibitors
• Other Study ID Numbers: Arise-FJ-B102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No