Pyrotinib in Combination With Letrozole in Patients With HER2-Positive, ER-Positive Metastatic Breast Cancer

Phase II Study of Pyrotinib in Combination With Letrozole in Patients With HER2-Positive, ER-Positive Metastatic Breast Cancer

This is a prospective, single-arm, multi-center clinical study of pyrotinib in combination With letrozole in patients With HER2-Positive, ER-Positive metastatic breast cancer. Our aim was to explore the efficacy and safety of pyrotinib combined with letrozole in patients with HER2-positive, ER-positive metastatic breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Pyrotinib Maleate plus Letrozole

Detailed Description

ER+/HER2+ metastatic breast cancer is a special subtype of HER2+ breast cancer. General guidelines recommend chemotherapy combined with HER2-targeted therapy for this subtype of patients. However, for the highly selected patients with ER- positive/HER2-positive ABC, ET + anti-HER2 therapy could be chosen as first-line therapy. And Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. Therefore this study is planned to enroll 86 patients with HER2-positive, ER-positive metastatic breast cancer receiving first-line treatment with pyrotinib and letrozole. The main purpose was to evaluate the efficacy and safety of pyrotinib combined with letrozole in patients with HER2-positive, ER-positive metastatic breast cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 86
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Quchang Ouyang, PhD; Phone Number: +86 13973135318; Email: Oyqc1969@126.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410006
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Quchang Ouyang, PhD; Phone Number: +86 13973135318; Email: Oyqc1969@126.com
      • Principal Investigator: Quchang Ouyang, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with HER2+/ER+ recurrent or metastatic breast cancer confirmed by histopathology;

   • HER2 positive: HER2 IHC 3+, or HER2 IHC 2+ and ISH positive
   • ER positive: the percentage of cells positive for ER expression ≥ 10%
2. Premenopausal, perimenopausal or postmenopausal patients (with OFS, if pre- or perimenopausal);
3. If the patient is bilateral breast cancer, metastasis lesions must be HER2 and ER positive;
4. 18-70 years old;
5. ECOG PS 0～1;
6. Life expectancy is not less than 12 weeks;
7. At least one measurable lesion according to RECIST 1.1;
8. Prior (neo) adjuvant trastuzumab, pertuzumab or chemotherapy were eligible, and the disease free interval must be greater than 12 months from completion of (neo) adjuvant trastuzumab and pertuzumab to metastatic diagnosis;
9. Prior (neo) adjuvant hormone therapy was allowed, if received adjuvant AI, the disease free interval must be greater than 12 months from the completion of treatment;
10. Disease-free Survival after surgery (DFS) ≥12 months;
11. Patients with adequate organ function before enrollment: ANC ≥ 1.5×109/L, PLT ≥ 75×109/L, Hb ≥ 100 g/L; TBIL≤1.0ULN；ALT and AST≤3×ULN (ALT and AST≤5×ULN if liver metastasis); BUN and Cr≤1.5×ULN and CCr≥50 mL/min; LVEF ≥ 50% and QTc < 480 ms;
12. Signed informed consent.

Exclusion Criteria:

1. Central nervous system metastasis;
2. patients with Visceral crisis;
3. Unable to swallow, chronic diarrhea and intestinal obstruction, there are many factors affecting drug use and absorption;
4. received radiotherapy, hormone therapy, chemotherapy, surgery (excluding local puncture) or molecular targeted therapy for advanced or metastatic disease;
5. received radiotherapy, chemotherapy, surgery (excluding local puncture) or molecular targeted therapy within 4 weeks prior to randomization;
6. Received hormone therapy within 2 weeks prior to randomization;
7. Participated in other clinical trial within 4 weeks prior to randomization;
8. Previous or ongoing use of HER2-targeted tyrosine kinase inhibitors (lapatinib, neratinib or pyrotinib);
9. Other malignancies within 5 years, except for cured skin basal cell carcinoma,carcinoma in-situ of uterine cervix and squamous-cell carcinoma;
10. Receive other anti-tumour therapy at the same time;
11. History of immunodeficiency, including HIV positive, HCV, active hepatitis B, or other acquired, congenital immunodeficiency disorders, or organ transplantation, is known;
12. History of any kind of Heart disease;
13. All female patients in pregnancy or breastfeeding period, fertile women with positive baseline pregnancy tests;
14. Evidence of significant medical illness that will substantially increase the risk on the participation or completion of the study in the investigator's judgment. Examples included, but not limited to, hypertension, severe diabetes, etc;
15. History of neurological or psychiatric disorders, including epilepsy or dementia;
16. Patients not eligible for this study judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pyrotinib plus Letrozole	Drug: Pyrotinib Maleate plus Letrozole; pyrotinib(400 mg once daily) + Letrozole (2.5 mg once daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit rate (CBR)	Ratio of CR,PR and SD greater than or equal to 24 weeks in all subjects	Estimated 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Ratio of CR and PR in all subjects	Estimated 12 months
Overall Survival (OS)	From enrollment to death (for any reason)	Estimated 24 months
Progression Free Survival (PFS)	From enrollment to progression or death (for any reason	Estimated 12 months
Adverse Events and Serious Adverse Events	Adverse events are described in terms of CTC AE 4.0	From informed consent through 28 days following treatment completion

Collaborators and Investigators

• Sponsor: Hunan Cancer Hospital
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Quchang Ouyang, PhD, Department of Breast Cancer Medical Oncology

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2019
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: May 25, 2020
• First Submitted That Met QC Criteria: May 25, 2020
• First Posted (Actual): May 29, 2020

Study Record Updates

• Last Update Posted (Actual): October 13, 2021
• Last Update Submitted That Met QC Criteria: October 12, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: HR-BLTN-008

Drug and device information, study documents

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