Phase II Clinical Study of T-DM1 and Pyrotinib Maleate in Patients With HER2-positive Metastatic Breast Cancer Who Had Progressed on TKI Therapy

A Prospective, Multicenter，Phase II Clinical Study of Trastuzumab and Pyrotinib Maleate in Patients With HER2-positive Metastatic Breast Cancer Who Had Progressed on TKI Therapy

This trial is a combination of trastuzumab and pyrotinib in the treatment of patients with HER2-positive metastatic breast cancer who have progressed on TKI therapy. A total of 50 patients were enrolled in the study design. Preliminary efficacy and safety in patients with HER2-positive metastatic breast cancer who have progressed on TKI therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: HER2+ Advanced Breast Cancer Patients Progressing on TKI Therapy
• Intervention / Treatment: Drug: Trastuzumab Emtansine for Injection; Drug: Pyrotinib Maleate Tablets

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chunfang Hao, PhD; Phone Number: 13602031629; Email: haochf@163.com

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. Female breast cancer patients aged ≥18 years and ≤75 years old
2. HER2 positive (IHC3+, or IHC2+ and positive FISH test) confirmed by the center
3. ECOG score 0-1
4. Patients with advanced breast cancer who have progressed on lapatinib or pyrotinib
5. There are measurable lesions
6. Left ventricular ejection fraction (LVEF) ≥ 50%
7. 12-lead ECG: Fridericia-corrected QT interval (QTcF) in women < 470 ms;
8. The function level of major organs must meet the following requirements: blood routine: ANC≥1.5×109/L; PLT≥90×109/L; Hb≥90g/L; blood biochemistry: TBIL≤2.5×ULN; ALT and AST≤2.5 ×ULN; BUN and Cr ≤ 1.5×ULN;
9. For female subjects who are not menopausal or surgically sterilized, agree to abstain from sex or use effective contraceptive methods during the treatment period and for at least 2 months after the last dose in the study treatment;
10. Voluntarily join the study, sign informed consent, have good compliance and be willing to cooperate with follow-up.

exclusion criteria：

1. Patients who have previously used ADCs to treat advanced breast cancer
2. Symptomatic patients with brain metastases
3. Control unstable pleural effusion and ascites patients
4. Patients with previous or concurrent malignancies whose natural medical history or treatment may interfere with the safety or efficacy assessment of the study protocol are not eligible to participate in this trial, except for basal cell or squamous cell skin cancer, cervical cancer in situ, or bladder cancer , or the subject has lived free of disease (other cancers) for at least 5 years.
5. Active infection requiring systemic treatment
6. Gastrointestinal dysfunction or disease that may seriously affect the absorption of the study drug (such as ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) or severely impair the ability to swallow capsules/tablets
7. Known history of myelodysplastic syndrome or acute myeloid leukemia
8. History of abdominal fistula, gastrointestinal perforation or abdominal abscess within 28 days
9. Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months
10. History of acute coronary syndrome (including myocardial infarction, unstable angina, coronary artery, arterial bypass grafting, coronary angioplasty or stenting) or symptomatic pericarditis within 6 years
11. Symptomatic congestive heart failure (New York Heart Association III-IV) or cardiomyopathy with left ventricular ejection fraction (LVEF) <50%
12. Clinically significant ventricular arrhythmia (sustained tachycardia/ventricular fibrillation) or high-grade AV block (eg, bifascicular block, Mobitz type II, and third-degree AV block), unless fitted pacemaker
13. Any concurrent severe and/or uncontrolled medical conditions that, in the judgment of the investigator, would result in unacceptable safety risks, prohibit subjects from participating in clinical studies, or affect protocol compliance

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: Trastuzumab Emtansine for Injection；Pyrotinib Maleate Tablets; Trastuzumab Emtansine for Injection: 3.6 mg/kg body weight (IV), administered on day 1, 21 days as a treatment cycle; Pyrotinib Maleate Tablets: The initial dose is 320 mg (PO), administered orally within 30 minutes after meals, at the same time every day, 21 days as a treatment cycle; Efficacy was assessed every two cycles and treatment was continued until disease progression or intolerable toxicity or death.

Drug: Trastuzumab Emtansine for Injection; 3.6 mg/kg body weight (IV), administered on day 1, 21 days as a treatment cycle; Drug: Pyrotinib Maleate Tablets; The initial dose is 320 mg (PO), administered orally within 30 minutes after meals, at the same time every day, 21 days as a treatment cycle;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR(objective response rate)	rate of CR and PR in all subjects	Estimated 24 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): September 30, 2022
• Primary Completion (Anticipated): August 31, 2024
• Study Completion (Anticipated): August 23, 2025

Study Registration Dates

• First Submitted: September 26, 2022
• First Submitted That Met QC Criteria: September 26, 2022
• First Posted (Actual): September 29, 2022

Study Record Updates

• Last Update Posted (Actual): October 3, 2022
• Last Update Submitted That Met QC Criteria: September 30, 2022
• Last Verified: September 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; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Trastuzumab; Maytansine; Ado-Trastuzumab Emtansine
• Other Study ID Numbers: BC- T-DM1

Drug and device information, study documents

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