Pyrotinib and Vinorelbine Tartrate Capsules With or Without Inetetamab for First Line Treatment in Patients With Trastuzumab-resistant HER2-positive Advanced Breast Cancer

Phase II Study of Pyrotinib and Vinorelbine Tartrate Capsules With or Without Inetetamab for First Line Treatment in Patients With Trastuzumab-resistant HER2-positive Advanced Breast Cancer

Trastuzumab resistance, which is a common therapeutic challenge in HER2 positive metastatic breast cancer, is not fully understood. Pyrotinib is an oral tyrosine kinase inhibitor targeting EGFR, HER-2 and HER-4 receptors. More general inhibition of ErbB family with pyrotinib could provide additional benefit. Inetetamab could bind to HER2 extracellular domain (ECD) with high affinity and inhibit proliferation of multiple HER2-overexpressing cancer cell lines as a single agent or in combination with trastuzumab. This study is designed to evaluate the efficacy and safety of pyrotinib and vinorelbine tartrate capsulesin with or without Inetetamab for first line treatment in patients with HER2 positive metastatic breast cancer who had early failure on or after trastuzumab treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Inetetamab; Drug: Pyrotinib; Drug: Vinorelbine

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhiyong Yu; Phone Number: +8613355312277; Email: drzhiyongyu@aliyun.com

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:

Histologically or cytologically confirmed invasive breast cancer HER2 status must be prospectively, centrally tested and be HER2-positive based on central laboratory assay results 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. Patients who have previously used pertuzumab will be allowed.

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pyrotinib and Vinorelbine with Inetetamab	Drug: Inetetamab; 8mg/kg iv day 1 followed by 6mg/kg iv day 1, cycled every 21 days; Drug: Pyrotinib; 400 mg once daily; Drug: Vinorelbine; Initial dose 70 mg/m2 on days 1 and 8 (capsules) If well tolerated, subsequently 90 mg/m2 on days 1 and 8. Capsules on day 1 to be taken at the hospital, and on day 8 at home.
Experimental: Pyrotinib and Vinorelbine without Inetetamab	Drug: Pyrotinib; 400 mg once daily; Drug: Vinorelbine; Initial dose 70 mg/m2 on days 1 and 8 (capsules) If well tolerated, subsequently 90 mg/m2 on days 1 and 8. Capsules on day 1 to be taken at the hospital, and on day 8 at home.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression free survival	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	from enrollment to progression or death (for any reason), assessed up to 3 years	3 years

Collaborators and Investigators

• Sponsor: Zhiyong Yu

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2021
• Primary Completion (Anticipated): January 31, 2023
• Study Completion (Anticipated): July 31, 2024

Study Registration Dates

• First Submitted: July 11, 2021
• First Submitted That Met QC Criteria: July 11, 2021
• First Posted (Actual): July 15, 2021

Study Record Updates

• Last Update Posted (Actual): July 15, 2021
• Last Update Submitted That Met QC Criteria: July 11, 2021
• Last Verified: July 1, 2021

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; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Vinorelbine
• Other Study ID Numbers: ShandongCHI-20

Drug and device information, study documents

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