A Study of Pyrotinib Plus Vinorelbine in Comparison With Treatment of Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer

NCT03997539 | Unknown Phase 2 DMC

• 1 other identifier: HR-BLTN-002
• Study Type: interventional
• Target: 256
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to identify the highest tolerable dose of pyrotinib in combination with vinorelbine and to assess the safety and efficacy of the combination in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer. The study will be conducted in two parts. In the first part, testing will be done on up to 12 subjects to determine the highest tolerable dose of pyrotinib and vinorelbine in patients with advanced solid tumors. In the second part of the study, we will compare the safety and efficacy of Pyrotinib + vinorelbine vs. Treatment of Physician's Choice in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab-Based Therapy.Participants will be treated until disease progression (PD), unmanageable toxicity, or study termination.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (2)

• maximum-tolerated dose (MTD)

  The maximum-tolerated dose (MTD) will be defined as the maximum dose level at which no more than one subject out of three experiences has a dose-limiting toxicity (DLT) upon completing two treatment cycle.

  42 days

• PFS as Assessed by the Investigator

  progression-free survival

  From enrollment to progression or death (for any reason),assessed up to 100 months

Secondary Outcomes (2)

• Objective Response Rate

  from enrollment to progression or death (for any reason), assessed up to 100 months

• OS

  from enrollment to death (for any reason).assessed up to 100 months

Study Arms (4)

pyrotinib 320mg + vinorelbine

EXPERIMENTAL

pyrotinib 320mg tablets administered daily by mouth, vinorelbine 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered OV on day 1 and day 8 of 21 day cycle. Treatment lasts for two cycles

Drug: Pyrotinib; Drug: vinorelbine

pyrotinib 400mg + vinorelbine

EXPERIMENTAL

pyrotinib 400mg tablets administered daily by mouth, vinorelbine 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered OV on day 1 and day 8 of 21 day cycle. Treatment lasts for two cycles

Drug: Pyrotinib; Drug: vinorelbine

Pyrotinib + vinorelbine

EXPERIMENTAL

pyrotinib administered daily by mouth（MTD）, vinorelbine 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered OV on day 1 and day 8 of 21 day cycle. Treatments will lasts until disease progression (as assessed by the investigator) or unmanageable toxicity.

Drug: Pyrotinib; Drug: vinorelbine

Treatment of physician's choice

ACTIVE COMPARATOR

Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and single-agent HER2-directed therapy.

Drug: Treatment of physician's choice

Interventions

Pyrotinib DRUG

Pyrotinib Maleate combine with vinorelbine as the second-line treatment to HER2-positive Metastatic Breast Cancer

Pyrotinib + vinorelbine; pyrotinib 320mg + vinorelbine; pyrotinib 400mg + vinorelbine

Treatment of physician's choice DRUG

The treatment of physician's choice (TPC) was a protocol-specified approved or standard of care therapy or combination of therapies, based on frequently used regimens for second-line HER2-positive metastatic breast cancer treatment after receipt of trastuzumab-containing regimens. The therapies included single-agent chemotherapy, single-agent (e.g., tamoxifen or aromatase inhibitor) or dual-agent (e.g., aromatase inhibitor with luteinizing hormone releasing hormone \[LHRH\] agonist) hormonal therapy for hormone receptor positive-disease, and single-agent HER2-directed therapy.

Treatment of physician's choice

vinorelbine DRUG

vinorelbine

Pyrotinib + vinorelbine; pyrotinib 320mg + vinorelbine; pyrotinib 400mg + vinorelbine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HER2 status must be prospectively, centrally tested and be HER2-positive based on central laboratory assay results
• Histologically or cytologically confirmed invasive breast cancer
• Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced, or metastatic setting must include both a taxane, alone or in combination with another agent, and trastuzumab, alone or in combination with another agent
• Documented progression (which occur during or after most recent treatment or within 6 months after completing of adjuvant therapy) of incurable, unresectable, locally advanced or metastatic breast cancer, defined by the investigator
• Measurable and/or nonmeasurable disease; participants with central nervous system-only disease are excluded
• Cardiac ejection fraction greater than or equal to (\>/=) 50 percent (%) by either echocardiogram or multi-gated acquisition scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

You may not qualify if:

• History of treatment with pyrotinib
• Prior treatment with lapatinib or neratinib
• History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma
• History of receiving any anti-cancer drug/biologic or investigational treatment within 28 days prior to randomization except hormone therapy
• Recovery of treatment-related toxicity consistent with other eligibility criteria
• History of radiation therapy within 28 days of randomization
• Brain metastases that are untreated, symptomatic, or require therapy to control symptoms, as well as any history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 2 months (60 days) of randomization
• History of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatment
• History of myocardial infarction or unstable angina
• Current severe, uncontrolled systemic disease (for example, clinically significant cardiovascular, pulmonary, or metabolic disease)
• Pregnancy or lactation
• Current known active infection with human immunodeficiency virus (HIV) or hepatitis C virus
• Presence of conditions that could affect gastrointestinal absorption: Malabsorption syndrome, resection of the small bowel or stomach, and ulcerative colitis

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pyrotinib; Vinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: clinical professor

Study Record Dates

• First Submitted: June 13, 2019
• First Posted: June 25, 2019
• Study Start: August 15, 2019
• Primary Completion: June 30, 2021
• Study Completion: December 30, 2021
• Last Updated: June 25, 2019

Record last verified: 2019-06