Adjuvant Dual Anti-HER2 Therapy in Patients With Small, Node-negative, HER2-positive Breast Cancer (SHERO)

Adjuvant Dual Anti-HER2 Therapy in Patients With Tumors < 8mm, Node-negative, HER2-positive Breast Cancer :a Single-group Arm, Open-label, Prospective, Phase 2 Study

This phase II trial aims to study the efficacy and safety of adjuvant Pyrotinib plus trastuzumab in patients with tumors <8mm, node-negative, HER2-positive breast cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Drug: Pyrotinib; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

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:

1. Women aged 18-70 years old
2. Have finished radical operation
3. Histologically confirmed invasive ductal carcinoma (IDCA)
4. According to AJCC ,pT<8mm, pN0, no evidence for metastasis
5. Operation specimens are available for ER, progesterone receptor (PR) and HER2 detection, patients should be HER2 positive tumor (IHC staining of 3+ [uniform, intense membrane staining of >30% of invasive tumor cells], or a FISH result of .6 HER2 gene copies per nucleus or a FISH ratio [HER2 gene signals to chromosome 17 signals] of >2.2), nuclear grade 3.
6. Should have tumor tissue available and sufficient for multi-spots sampling.
7. It has been <84 days since the date of definitive surgery, and there is adequate wound healing as determined by the Treating Physician.
8. Has Eastern Cooperative Oncology Group (ECOG) Performance Score 0-1, expected survival time > 12 months
9. Cardiac function had to be within normal limits (left ventricular ejection fraction [LVEF] ≥50%), as established by multiple gated acquisition scan or echocardiography.
10. Adequate bone marrow function, adequate liver and renal function, and adequate coagulation function.
11. Women with potential child-bearing must have a negative pregnancy test (urine or serum) within 7 days of drug administration and agree to use an acceptable and effective method of contraception to avoid pregnancy during the study.
12. Written informed consent according to the local ethics committee requirements.

Exclusion Criteria:

1. pT≥8mm or node positive
2. Metastatic breast cancer
3. Any prior systemic or loco-regional treatment of breast cancer, including chemotherapy in 28 days
4. With a history of malignant tumor except uterine cervix cancer in situ or skin basal cell carcinoma
5. Patients with medical conditions that indicate intolerant to adjuvant target therapy and related treatment, including severe infection, coagulation disorder, active peptic ulcer, coagulation disorder, connective tissue disease or myelo-suppressive disease
6. Has symptomatic peripheral neuropathy > grade 2 according to NCI
7. Known severe allergy to any drugs in this study

8. Has cardiac dysfunction or lung dysfunction defined as follows:

   • grade ≥3 CHF according to NCI CTCAE v 5.0 or NYHA≥II
   • angina which requires drug control, cardiac infraction, and any other vascular disease with apparent clinical symptoms
   • uncontrolled high-risk arrhythmia
   • uncontrolled hypertension
9. Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is known to be HIV positive
10. Patient is pregnant or breast feeding

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: Experimental Arm; adjuvant Pyrotinib plus Trastuzumab	Drug: Pyrotinib; 400mg po every day; Other Names: Pyrotinib Maleate Tablets; Drug: Trastuzumab; Trastuzumab is administered at a loading dose of 8 mg/kg IV followed by 6 mg/kg every 21 days; Other Names: Herceptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival	stimated percentage of patients alive and disease-free at 5 years from randomization or censored at date of last follow-up.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breast Cancer Specific Survival	Estimated percentage of patients alive and disease-free at 5 years from randomization, where breast cancer specific survival is defined as the time from randomization to death from breast cancer relapse; or censored at date last known alive.	5 years
Overall Survival	Estimated percentage of patients alive and disease-free at 5 years from randomization, where overall survival is defined as the time from randomization to death from any cause; or censored at date last known alive.	5 years
Treatment-related adverse events	Incidence and severity of adverse events as assessed by NCI CTCAE V5.0	up to 3 months
Change of LVEF after treatment	The change of LVEF after 3 months treatment compared to the baseline LVEF	up to 3 months

Collaborators and Investigators

• Sponsor: xuexin he
• Investigators: Study Chair: Xuexin He, MD, Seaond Affiliated Hospital, Zhejiang University, School of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): May 31, 2023
• Study Completion (Anticipated): May 31, 2030

Study Registration Dates

• First Submitted: November 7, 2019
• First Submitted That Met QC Criteria: November 7, 2019
• First Posted (Actual): November 12, 2019

Study Record Updates

• Last Update Posted (Actual): November 12, 2019
• Last Update Submitted That Met QC Criteria: November 7, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: SHERO

Drug and device information, study documents

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