NCT04398914

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
216

participants targeted

Target at P75+ for phase_2

Timeline
20mo left

Started May 2020

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress78%
May 2020Dec 2027

First Submitted

Initial submission to the registry

May 19, 2020

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 22, 2020

Completed
8 days until next milestone

Study Start

First participant enrolled

May 30, 2020

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 30, 2022

Completed
5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2027

Expected
Last Updated

March 31, 2022

Status Verified

March 1, 2022

Enrollment Period

2.6 years

First QC Date

May 19, 2020

Last Update Submit

March 28, 2022

Conditions

Breast Cancer Invasive

Keywords

HER2-positiveStage II-III

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With Total Pathologic Complete Response (tpCR)

    tpCR is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current American Joint Committee on Cancer \[AJCC\] staging system).The duration of one treatment cycle is 21 days.

    After completion of 4 cycles of neoadjuvant therapy. The duration of one treatment cycle is 21 days

Secondary Outcomes (5)

  • Percentage of Participants With Breast Pathologic Complete Response (bpCR)

    After completion of 4 cycles of neoadjuvant therapy The duration of one treatment cycle is 21 days. at the time of surgery

  • Clinical response

    Cycle 1-4. The duration of one treatment cycle is 21 days.

  • Event-free survival (EFS)

    From Baseline to EFS event or date last known to be alive and event-free (up to 5 years)

  • Disease-free survival (DFS)

    From surgery to DFS event or date last known to be alive and event-free (up to 5 years)

  • Overall survival (OS)

    From Baseline to OS event or date last known to be alive (up to 5 years)

Other Outcomes (1)

  • Percentage of Participants With At Least One Adverse Event During Treatment Period

    From randomization to 30 days after completion of study treatment

Study Arms (2)

Pyrotinib, trastuzumab, pertuzmab and paclitaxel

EXPERIMENTAL

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.

Drug: PyrotinibDrug: TrastuzumabDrug: PertuzumabDrug: Nab-paclitaxelDrug: EC chemotherapyDrug: Physician's choiceDrug: T-DM1Procedure: Surgery

Trastuzumab, pertuzmab and paclitaxel

ACTIVE COMPARATOR

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.

Drug: TrastuzumabDrug: PertuzumabDrug: Nab-paclitaxelDrug: EC chemotherapyDrug: Physician's choiceDrug: T-DM1Procedure: Surgery

Interventions

PyrotinibDRUG

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

Pyrotinib, trastuzumab, pertuzmab and paclitaxel
TrastuzumabDRUG

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

Pyrotinib, trastuzumab, pertuzmab and paclitaxelTrastuzumab, pertuzmab and paclitaxel
PertuzumabDRUG

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

Pyrotinib, trastuzumab, pertuzmab and paclitaxelTrastuzumab, pertuzmab and paclitaxel
Nab-paclitaxelDRUG

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

Pyrotinib, trastuzumab, pertuzmab and paclitaxelTrastuzumab, pertuzmab and paclitaxel
EC chemotherapyDRUG

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

Pyrotinib, trastuzumab, pertuzmab and paclitaxelTrastuzumab, pertuzmab and paclitaxel
Physician's choiceDRUG

Physician decided chemotherapy for 0-4 cycles.

Pyrotinib, trastuzumab, pertuzmab and paclitaxelTrastuzumab, pertuzmab and paclitaxel
T-DM1DRUG

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

Pyrotinib, trastuzumab, pertuzmab and paclitaxelTrastuzumab, pertuzmab and paclitaxel
SurgeryPROCEDURE

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

Pyrotinib, trastuzumab, pertuzmab and paclitaxelTrastuzumab, pertuzmab and paclitaxel

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Interventions

pyrotinibTrastuzumabpertuzumab130-nm albumin-bound paclitaxelSurgical Procedures, Operative

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Kunwei Shen, MD,PhD

    Ruijin Hospital

    STUDY CHAIR

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
Professor

Study Record Dates

First Submitted

May 19, 2020

First Posted

May 22, 2020

Study Start

May 30, 2020

Primary Completion

December 30, 2022

Study Completion (Estimated)

December 30, 2027

Last Updated

March 31, 2022

Record last verified: 2022-03

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)