Efficacy and Safety Study of EG12014 Compared With Herceptin in Subjects With HER2 Positive Early Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase III, Randomized, Multicenter, Double-blind Study to Compare Efficacy and Safety of EG12014 With Herceptin as Neoadjuvant Treatment in Combination With Anthracycline/Paclitaxel Systemic Therapy in HER2-Positive Early Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03433313
• Other study ID #: EGC002
• Secondary ID: 2017-003973-33
• Status: Completed
• Phase: Phase 3
• Start date: October 16, 2018
• Est. completion date: January 20, 2022

Study information

• Verified date: January 2023
• Source: EirGenix, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this research study is to compare the efficacy and safety of EG12014 with Herceptin as neoadjuvant treatment for 12 weeks, followed by surgery and subsequent EG12014 or Herceptin adjuvant treatment for up to 12 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 807
• Est. completion date: January 20, 2022
• Est. primary completion date: January 20, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

1. Provide signed and dated written informed consent before entering the study. The informed consent will cover both parts of the study (neoadjuvant part and adjuvant part).

2. Female, =18 and =65 years of age.

3. Histologically-confirmed invasive carcinoma of the breast (American Joint Committee on Cancer [AJCC, vs. 8.0] Stage II, IIIa).

4. Operable breast cancer, planned surgical resection of breast tumor (mastectomy or lumpectomy) and sentinel or axillary lymph nodes.

5. Unilateral, measurable tumor of the breast >2 cm in diameter.

6. HER2 positive tumor, defined as 3+ score by IHC or fluorescence positive by FISH, as confirmed by central laboratory.

7. Known estrogen receptor (ER) and progesterone receptor (PrR) status at study entry.

8. Adequate bone marrow function, defined as granulocyte count of =1.500/µL, and platelet count of =100.000/µL.

9. Adequate hepatic and renal function, defined as:

bilirubin within normal range

alanine aminotransferase (ALT) =2 x upper limit of normal (ULN)

aspartate aminotransferase (AST) =2 x ULN

gamma glutamyl transferase (GGT) =3 x ULN

serum creatinine <1.5 ULN

10. International normalized ratio =1.5×ULN (2 to 3×ULN if on anticoagulants) or prothrombin time =1.5×ULN; activated partial thromboplastin time =1.5×ULN.

11. Hemoglobin concentrations =10 g/dL.

12. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.

13. LVEF =55%, measured by multiple-gated acquisition (MUGA) scan or echocardiography.

14. Negative pregnancy test at entry, women of childbearing potential have to use contraceptives during the course of the study.

Females with childbearing potential must provide a negative serum pregnancy test at Screening and must be using adequate birth control. Adequate birth control is defined as agreement to consistently practice an effective and accepted method of contraception throughout the duration of the study and for 7 months after study drug treatment. These methods include hormonal contraceptives, intrauterine device, or double barrier contraception (i.e., condom + diaphragm) or a male partner with documented vasectomy.

Non-childbearing potential is defined as post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months before study start.

Exclusion Criteria:

1. Bilateral breast cancer.

2. Pregnancy or lactation or considering becoming pregnant.

3. Metastases, other than sentinel/axillary lymph nodes.

4. Previous treatment (chemotherapy, biologic therapy, radiation, or surgery) for invasive malignant disease or other concomitant malignancy, other than basal cell carcinoma of the skin. Previous treatment for carcinoma in situ of the cervix is allowed.

5. Previous treatment with Herceptin.

6. Angina pectoris or arrhythmia requiring medication; poorly controlled hypertension; history of myocardial infarction or cardiac failure, New York Heart Association (NYHA) class II or higher; clinically significant cardiac valvular disease; hemodynamic effective pericardial effusion; other cardiomyopathies; LVEF of <55%.

7. Any investigational treatment less than 30 days prior to study entry, or within a time interval less than at least 5 half-lives of the investigational medicinal product, whichever is longer.

8. Positive diagnostic test for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).

9. History of hypersensitivity to drugs with similar chemical structures to trastuzumab.

10. History of, or known current problems with, drug or alcohol abuse.

11. Other serious illness, medical disorder or condition that, in the opinion of the Investigator, would make the patient unsuitable for participation in the study.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• EG12014
EG12014 6mg/kg is ongoing to be administered after 8mg/kg loading dose.
• Herceptin
Herceptin 6mg/kg is ongoing to be administered after 8mg/kg loading dose.

Locations

Country	Name	City	State
Belarus	Brest Regional Oncology Center	Brest
Belarus	Gomel Regional Clinical Oncology Center	Gomel
Belarus	N.N. Aleksandrov Republican Research Oncology and Medical Radiology Center	Lesnoy
Belarus	Minsk City Clinical Oncology Center	Minsk
Belarus	Mogilev Regional Oncology Center	Mogilev
Belarus	Vitebsk Regional Clinical Oncology Center	Vitebsk
Chile	Medical Research Limited Society	Temuco
Chile	Oncocentro Apys	Viña Del Mar
Colombia	Clinic Life Foundation	Medellín
Colombia	Rodrigo Botero SAS	Medellín
Georgia	LTD High-Tech Hospital MedCenter	Batumi
Georgia	JSC "Evex Hospitals	Kutaisi
Georgia	LTD Acad. F. Todua Medical Center - LTD Research Institute of Clinical Medicine	Tbilisi
Georgia	LTD Aversi Clinic	Tbilisi
Georgia	LTD Cancer Research Centre	Tbilisi
Georgia	LTD Health House	Tbilisi
Georgia	LTD Institute of Clinical Oncology	Tbilisi
Georgia	LTD S.Khechinashvili University Hospital	Tbilisi
Georgia	Malkhaz Katsiashvili Multiprofile Emergency Medicine Center	Tbilisi
India	Cytecare Cancer Hospitals	Bengaluru
India	King George's Medical University, Department of Endocrine surgery, Shatabdi Phase II	Lucknow
India	Tata Memorial Centre	Mumbai
India	HCG NCHRI Cancer Centre	Nagpur
India	Christian Medical College, Department of Medical Oncology	Vellore
Korea, Republic of	Keimyung University - Dongsan Medical Center	Daegu
Russian Federation	Arkhangelsk Clinical Oncology Center	Arkhangel'sk
Russian Federation	Chelyabinsk Regional Clinical Oncology and Nuclear Medicine Center	Chelyabinsk
Russian Federation	Evimed, LLC	Chelyabinsk
Russian Federation	Ivanovo Regional Oncology Center	Ivanovo
Russian Federation	Republican Clinical Oncology Center	Kazan
Russian Federation	Krasnoyarsk A.I. Kryzhanovsky Regional Oncology Center	Krasnoyarsk
Russian Federation	Kursk Regional Clinical Oncology Center	Kursk
Russian Federation	N.N. Blokhin National Medical Oncology Research Center	Moscow
Russian Federation	National Medical Research Center for Radiology	Moscow
Russian Federation	Vitamed" LLC	Moscow
Russian Federation	A.F.Tsyb Medical Radiology Research Center	Obninsk
Russian Federation	Clinical Oncology Center	Omsk
Russian Federation	Pyatigorsk Interdistrict Oncology Center	Pyatigorsk
Russian Federation	Rostov Oncology Research Institute	Rostov-on-Don
Russian Federation	Regional Clinical Oncology Center	Ryazan'
Russian Federation	AV Medical Group	Saint Petersburg
Russian Federation	City Clinical Oncology Center	Saint Petersburg
Russian Federation	Clinic "Mart"	Saint Petersburg
Russian Federation	I.I. Mechnikov North-Western State Medical University	Saint Petersburg
Russian Federation	Leningrad Regional Oncology Center (Outpatient Department)	Saint Petersburg
Russian Federation	Leningrad Regional Oncology Center (Surgery Department)	Saint Petersburg
Russian Federation	N.N. Petrov National Medical Research Center of Oncology	Saint Petersburg
Russian Federation	Oncology Center of Moskovskiy District	Saint Petersburg
Russian Federation	Private Medical Institution "EVROMEDSERVIS", Department of Oncology	Saint Petersburg
Russian Federation	St. Petersburg Clinical Research and Practical Center for Specialized Types of Medical Care (Oncology)	Saint Petersburg
Russian Federation	Republican Oncology Center	Saransk
Russian Federation	Oncology Center #2	Sochi
Russian Federation	Tomsk National Research Medical Center	Tomsk
Russian Federation	Regional Clinical Oncology Center	Veliky Novgorod
Russian Federation	Volgograd Regional Clinical Oncology Center	Volgograd
South Africa	GVI Oncology, Cape Gate Oncology Centre	Cape Town
South Africa	The Oncology Centre	Durban
South Africa	Medical Oncology Centre of Rosebank	Johannesburg
South Africa	Little Company of Mary Medical Center, Department of Oncology	Pretoria
South Africa	University of Pretoria, Department of Medical Oncology	Pretoria
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan
Ukraine	Chernihiv Regional Oncology Center	Chernihiv
Ukraine	Chernivtsi Regional Clinical Oncology Center	Chernivtsi
Ukraine	Clinical Oncology Center	Dnipro
Ukraine	Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy	Dnipro
Ukraine	Prikarpattia Clinical Oncology Center	Ivano-Frankivsk
Ukraine	Communal Non-profit enterprise "Regional Center of Oncology"	Kharkiv
Ukraine	State Institution: S.P. Hryhoriev Institute of Medical Radiology under the Ukrainian Academy of Medical Sciences, Department of Clinical Oncology and Hematology	Kharkiv
Ukraine	Khmelnytskyi Regional Oncology Center	Khmelnytskyi
Ukraine	Kryvyi Rih Oncology Center, Department of Chemotherapy	Kryvyi Rih
Ukraine	Kyiv City clinical Hospital #2	Kyiv
Ukraine	Kyiv Regional Oncology Center, Department of Mastology	Kyiv
Ukraine	Medical Center "Verum"	Kyiv
Ukraine	Medical Center of First Private Clinic	Kyiv
Ukraine	Volyn Regional Oncology Center, Department of Chemotherapy	Luts'k
Ukraine	Public Institution under Lviv Regional Council: Lviv Regional Treatment and Diagnostics Oncology Center, Department of Chemotherapy	Lviv
Ukraine	Mariupol Oncology Center	Mariupol
Ukraine	Odesa Regional Clinical Hospital, Center for Mastology, Department of Thoracic Surgery	Odesa
Ukraine	Odesa Regional Oncology Center	Odesa
Ukraine	Ternopil Regional Clinical Oncology Center, Department of Chemotherapy	Ternopil'
Ukraine	Central City Clinical Hospital, Department of Oncology and Radiology	Uzhhorod
Ukraine	Zakarpattia Regional Clinical Oncology Center, Department of Chemotherapy	Uzhhorod
Ukraine	Podillia Regional Oncology Center	Vinnytsia
Ukraine	Zhytomyr Regional Oncology Center	Zhytomyr
United States	Aultman Hospital, Cancer Center	Canton	Ohio
United States	Detroit Clinical Research Center	Farmington Hills	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
EirGenix, Inc.

Countries where clinical trial is conducted

United States,  Belarus,  Chile,  Colombia,  Georgia,  India,  Korea, Republic of,  Russian Federation,  South Africa,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of pathologic complete response (pCR) at time of surgery	pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled sentinel and/or axillary lymph nodes	At the time of surgery (3-6 weeks after completion of neoadjuvant chemotherapy)
Secondary	pCR at the time of surgery	pCR is defined as the absence of residual invasive cancer and of DICS (ypT0 ypN0) from breast tissue and sentinel/axillary lymph nodes, as assessed by central laboratory	At the time of surgery (3-6 weeks after completion of neoadjuvant chemotherapy)
Secondary	pCR at the time of surgery	pCR is defined as the absence of invasive cancer in breast tissue only (ypT0/is) as assessed by central laboratory	At the time of surgery (3-6 weeks after completion of neoadjuvant chemotherapy)
Secondary	Event-free survival (EFS) up to end of study (EOS)	EFS is defined as time from initial randomization to the date when disease recurrence or progression (local, regional, distant or contralateral) is diagnosed according to institutional standard, or date of death of any cause, whichever is earlier	Randomization to date of progression or end of study (up to approximately 24 months or death)
Secondary	Overall response (OR) prior to surgery	Objective response is defined as partial response (PR) or complete response (CR) according to RECIST v1.1	At screening and prior to surgery (3-6 weeks after completion of neoadjuvant chemotherapy)
Secondary	Overall survival (OS) up to End of Study (EOS)	OS up to EOS is defined as time from the date of initial randomization to the date of death	Randomization to end of study (up to approximately 24 months or death)
Secondary	Incidence of AEs	Incidence of AEs (including severity, seriousness, and relationship to study drug) and laboratory abnormalities	From time of informed consent to end of study (up to approximately 25 months or death)
Secondary	Evaluation of Immunogenicity of EG12014 and Herceptin	Titer of anti-drug antibodies (ADA)	Prior to 1st infusion of study drug, during neoadjuvant treatment, after the last dose of neoadjuvant treatment, during adjuvant treatment, and End of Treatment
Secondary	Measure serum trastuzumab concentration	Measure serum trastuzumab concentration for EG12014 and Herceptin arms	Prior to 1st infusion of study drug, during neoadjuvant treatment after the last dose of neoadjuvant treatment, during adjuvant treatment, and End of Treatment