A Study of Pyrotinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer

Pyrotinib Plus Capecitabine Versus Placebo Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer:a Randomised, Double-blind, Multicentre, Phase 3 Trial

Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This study is a randomized, multi-center, multinational, double blind, active-controlled, parallel design study of the combination of pyrotinib in combination with capecitabine versus placebo plus capecitabine in HER2+ MBC patients, who have prior received anthracyclin, taxane and trastuzumab.

Patients will be randomized in a 2:1 ratio to one of the following treatment arms:

Arm A: pyrotinib (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Arm B: placebo (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Patients will receive either arm of therapy until the occurrence of death, disease progression, unacceptable toxicity, or other specified withdrawal criterion.

Patients in control group can be provide pyrotinib treatment when they progressed after the placebo plus capecitabine treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: HER2 Positive Metastatic Breast Cancer
• Intervention / Treatment: Drug: pyrotinib; Drug: Capecitabine; Drug: placebo

Detailed Description

This study is a phase 3, randomized, multi-center, multinational, double blind, active-controlled, parallel design study of the combination of pyrotinib in combination with capecitabine versus placebo plus capecitabine in HER2+ MBC patients, who have prior received anthracyclin, taxane and trastuzumab.

Patients will be randomized in a 2:1 ratio to one of the following treatment arms:

Arm A: pyrotinib (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Arm B: placebo (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Patients will receive either arm of therapy until the occurrence of death, disease progression, unacceptable toxicity, or other specified withdrawal criterion.

Efficacy assessments will be performed at screening, every 6 weeks until cycle 18, every 12 weeks thereafter.

Patients in control group can be provide pyrotinib treatment when they progressed after the placebo plus capecitabine treatment. Pyrotinb will be administrated until the patients reached progress again or wit

• Study Type: Interventional
• Enrollment (Actual): 279
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • 307 Hospital Affiliated to Academy Military Medical Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Aged ≥18 and ≤75 years.
2. ECOG performance status of 0 to 1.
3. Life expectancy of more than 12 weeks.
4. According to RECIST 1.1, at least one measurable lesion exists
5. Histologically or cytologic confirmed HER2 positive advanced breast cancer which failed prior therapies.
6. Prior treatment with trastuzumab(≥2 cycles in the metastatic setting, or ≥3 months in adjuvant setting), and the patients are not available for the trastuzumab or lapatinib
7. Previously reveived both Anthracyclin and Taxane.

8. Required laboratory values including following parameters:

   ANC: ≥ 1.5 x 10^9/L; Platelet count: ≥ 90 x 10^9/L; Hemoglobin: ≥ 9.0 g/dL; Total bilirubin: ≤ 1.5 x upper limit of normal (ULN); ALT and AST: ≤ 2 x ULN(patients with liver metastases: </= 5 x ULN); BUN and Creatinine: ≤ 1.5 x ULN;LVEF: ≥ 50%;QTcF: < 470 ms.

9. Signed informed consent

Exclusion Criteria:

1. Received previous therapy with lapatinib, neratinib, pyrotinib or any other HER2 directe tyrosine kinase inhibitor.
2. Received previous therapy with capecitabine.
3. History of receiving chemotherapy, target-therapy or investigational treatment within 28 days prior to randomization. Received hormone therapy within 7 days prior to randomization.
4. Brain metastases that are untreated, symptomatic, or require therapy to control symptoms.
5. Current severe, uncontrolled systemic disease.
6. Unable or unwilling to swallow tablets.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: arm 1; pyrotinib plus capecitabine pyrotinib(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID)	Drug: pyrotinib; 400 mg once daily; Drug: Capecitabine; 1000 mg/m2 per day on day 1 through 14, every 21 days.
Active Comparator: arm 2; placebo plus capecitabine placebo(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID)	Drug: Capecitabine; 1000 mg/m2 per day on day 1 through 14, every 21 days.; Drug: placebo; 400 mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival (PFS)	Estimated 10 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	Estimated 10 months
Safety(adverse Events [AEs] and Serious Adverse Events [SAEs])	From infromed consent through 28 days following treatment completion
Duration of Response (DOR)	Estimated 10 months
Clinical Benefit rate (CBR)	Estimated 10 months
Overall Survival (OS)	Estimated 30 months

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2016
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: November 22, 2016
• First Submitted That Met QC Criteria: November 22, 2016
• First Posted (Estimate): November 25, 2016

Study Record Updates

• Last Update Posted (Actual): October 25, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: HR-BLTN-Ⅲ-MBC-A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES