Pyrotinib, Trastuzumab, Pertuzumab and Nab-paclitaxel as Neoadjuvant Therapy in HER2-positive Breast Cancer

NCT ID: NCT04398914

Last Updated: 2022-03-31

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 216 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-30
• Study Completion Date: 2027-12-30

Brief Summary

This study aims to evaluate the efficacy and safety of pyrotinib in combination with trastuzumab, pertuzumab and nab-paclitaxel as neoadjuvant therapy in early stage or locally advanced HER2-positive breast cancer.

Detailed Description

The study evaluate the pathological complete response rate, event-free survival, disease-free survival, overall survival and safety of pyrotinib in combination with trastuzumab, pertuzumab and nab-paclitaxel as neoadjuvant therapy in early stage or locally advanced HER2-positive breast cancer. Patients will receive 4 cycles of pyrotinib in combination with trastuzumab, pertuzumab and nab-paclitaxel or 4 cycles of trastuzumab, pertuzumab and nab-paclitaxel as neoadjuvant therapy, then undergo surgery, then receive adjuvant chemotherapy and targeted therapy according to pathologic response and physician's choice.

Conditions

Breast Cancer Invasive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pyrotinib, trastuzumab, pertuzmab and paclitaxel

Prior to surgery: pyrotinib, trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).

After surgery：

• if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
• if tpCR: chemotherapy 0-4 cycles according to physician's choice, followed with pertuzumab and trastuzumab up to 1 year total.

Group Type: EXPERIMENTAL

Pyrotinib

Intervention Type: DRUG

Pyrotinib 400 mg taken orally everyday, every 3 weeks, for 4 cycles.

Trastuzumab

Intervention Type: DRUG

Trastuzumab IV infusion in 3-week cycles.

Neoadjuvant treatment: 8 milligrams per kilogram (mg/kg) loading dose for Cycle 1, followed by 6 mg/kg for Cycles 2-4.

Adjuvant treatment: 8 mg/kg loading dose, followed by 6 mg/kg for remaining cycles till completion of 1 year trastuzumab

Pertuzumab

Intervention Type: DRUG

Pertuzumab IV infusion in 3-week cycles.

Neoadjuvant treatment: 840 milligrams (mg) loading dose for Cycle 1, followed by 420 mg for Cycles 2-4.

Adjuvant treatment: 840 mg loading dose, followed by 420mg for remaining cycles till completion of 1 year pertuzumab

Nab-paclitaxel

Intervention Type: DRUG

Nab-paclitaxel 100mg/m2 by intravenous (IV) infusion on day1, day8 and day15, every 3 weeks, for 4 cycles.

EC chemotherapy

Intervention Type: DRUG

Epirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2 by intravenous (IV) infusion every 3 weeks for 4 cycles (Cycles 5-8)

Physician's choice

Intervention Type: DRUG

Physician decided chemotherapy for 0-4 cycles.

T-DM1

Intervention Type: DRUG

T-DM1 IV infusion in 3-week cycles. 3.6 mg/kg by intravenous (IV) infusion every 3 weeks for 14 cycles

Surgery

Intervention Type: PROCEDURE

All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.

Trastuzumab, pertuzmab and paclitaxel

Prior to surgery: trastuzumab, pertuzumab and nab-paclitaxel for 4 cycles (1 cycle = 21 days).

After surgery：

• if non-tpCR：chemotherapy with epirubicin and cyclophosphamide (EC), followed with pertuzumab and trastuzumab up to 1 year total; or T-DM1 for 14 cycles.
• if tpCR: chemotherapy 0-4 cycles according to physician's choice; followed with pertuzumab and trastuzumab up to 1 year total.

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: DRUG

Trastuzumab IV infusion in 3-week cycles.

Neoadjuvant treatment: 8 milligrams per kilogram (mg/kg) loading dose for Cycle 1, followed by 6 mg/kg for Cycles 2-4.

Adjuvant treatment: 8 mg/kg loading dose, followed by 6 mg/kg for remaining cycles till completion of 1 year trastuzumab

Pertuzumab

Intervention Type: DRUG

Pertuzumab IV infusion in 3-week cycles.

Neoadjuvant treatment: 840 milligrams (mg) loading dose for Cycle 1, followed by 420 mg for Cycles 2-4.

Adjuvant treatment: 840 mg loading dose, followed by 420mg for remaining cycles till completion of 1 year pertuzumab

Nab-paclitaxel

Intervention Type: DRUG

Nab-paclitaxel 100mg/m2 by intravenous (IV) infusion on day1, day8 and day15, every 3 weeks, for 4 cycles.

EC chemotherapy

Intervention Type: DRUG

Epirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2 by intravenous (IV) infusion every 3 weeks for 4 cycles (Cycles 5-8)

Physician's choice

Intervention Type: DRUG

Physician decided chemotherapy for 0-4 cycles.

T-DM1

Intervention Type: DRUG

T-DM1 IV infusion in 3-week cycles. 3.6 mg/kg by intravenous (IV) infusion every 3 weeks for 14 cycles

Surgery

Intervention Type: PROCEDURE

All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.

Interventions

Pyrotinib

Pyrotinib 400 mg taken orally everyday, every 3 weeks, for 4 cycles.

Intervention Type: DRUG

Trastuzumab

Trastuzumab IV infusion in 3-week cycles.

Neoadjuvant treatment: 8 milligrams per kilogram (mg/kg) loading dose for Cycle 1, followed by 6 mg/kg for Cycles 2-4.

Adjuvant treatment: 8 mg/kg loading dose, followed by 6 mg/kg for remaining cycles till completion of 1 year trastuzumab

Intervention Type: DRUG

Pertuzumab

Pertuzumab IV infusion in 3-week cycles.

Neoadjuvant treatment: 840 milligrams (mg) loading dose for Cycle 1, followed by 420 mg for Cycles 2-4.

Adjuvant treatment: 840 mg loading dose, followed by 420mg for remaining cycles till completion of 1 year pertuzumab

Intervention Type: DRUG

Nab-paclitaxel

Nab-paclitaxel 100mg/m2 by intravenous (IV) infusion on day1, day8 and day15, every 3 weeks, for 4 cycles.

Intervention Type: DRUG

EC chemotherapy

Epirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2 by intravenous (IV) infusion every 3 weeks for 4 cycles (Cycles 5-8)

Intervention Type: DRUG

Physician's choice

Physician decided chemotherapy for 0-4 cycles.

Intervention Type: DRUG

T-DM1

T-DM1 IV infusion in 3-week cycles. 3.6 mg/kg by intravenous (IV) infusion every 3 weeks for 14 cycles

Intervention Type: DRUG

Surgery

All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• With signed consent
• Histologically confirmed invasive breast carcinoma with a primary tumor size of no less than (≥) 2 centimeters (cm) by standard local assessment technique
• Breast cancer stage at presentation: stage II-III
• HER2-positive breast cancer defined as 3+ score by immunohistochemistry in > 10 percent (%) of immunoreactive cells or HER2 gene amplification by in situ hybridization
• Known hormone receptor status (estrogen receptor and/or progesterone receptor)
• Eastern Cooperative Oncology Group Performance Status equal to or less than (<=) 1
• Baseline left ventricular ejection fracture >= 50% measured by echocardiography
• Willing to use highly effective form of nonhormonal contraception while on study and for 7 months after end of study treatment for female with fertility or male
• Willing to obey the study protocol

Exclusion Criteria

• Stage IV disease
• Previous anti-cancer therapy or radiotherapy for any malignancy
• History of other malignancy within 5 years prior to screening, except for appropriately-treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, ,Stage I uterine cancer or thyroid papillary microcarcinoma
• Concurrent anti-cancer treatment in another investigational trial, including hormone therapy, bisphosphonate therapy, or immunotherapy
• Major surgical procedure unrelated to breast cancer within 4 weeks prior to randomization or from which the participant has not fully recovered
• Serious cardiac illness or medical condition
• Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
• Any abnormalities in liver, kidney or hematologic function laboratory tests immediately prior to randomization
• Sensitivity to any of the study medications, any of the ingredients or excipients of these medications, or benzyl alcohol
• Not able to swallow the drug
• Pregnant or lactating
• Positive serum or urine pregnancy test or above mentioned tests cannot be achieved for women with fertility

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu HengRui Medicine Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Kunwei Shen

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kunwei Shen, MD,PhD

Role: STUDY_CHAIR

Ruijin Hospital

Locations

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Countries

China

Other Identifiers

RJBC2001

Identifier Type: -

Identifier Source: org_study_id