Clinical trial NCT03433313: Efficacy and Safety Study of EG12014 Compared With Herceptin in Subjects With HER2 Positive Early Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: EirGenix, Inc.
Sponsor class: INDUSTRY
First posted: 2018-02-14
Enrollment: 807
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Determination of pathologic complete response (pCR) at time of surgery
timeFrame: At the time of surgery (3-6 weeks after completion of neoadjuvant chemotherapy)
Secondary outcomes:
measure: pCR at the time of surgery
timeFrame: At the time of surgery (3-6 weeks after completion of neoadjuvant chemotherapy)
measure: pCR at the time of surgery
timeFrame: At the time of surgery (3-6 weeks after completion of neoadjuvant chemotherapy)
measure: Event-free survival (EFS) up to end of study (EOS)
timeFrame: Randomization to date of progression or end of study (up to approximately 24 months or death)
measure: Overall response (OR) prior to surgery
timeFrame: At screening and prior to surgery (3-6 weeks after completion of neoadjuvant chemotherapy)
measure: Overall survival (OS) up to End of Study (EOS)
timeFrame: Randomization to end of study (up to approximately 24 months or death)
measure: Incidence of AEs
timeFrame: From time of informed consent to end of study (up to approximately 25 months or death)
measure: Evaluation of Immunogenicity of EG12014 and Herceptin
timeFrame: Prior to 1st infusion of study drug, during neoadjuvant treatment, after the last dose of neoadjuvant treatment, during adjuvant treatment, and End of Treatment
measure: Measure serum trastuzumab concentration
timeFrame: Prior to 1st infusion of study drug, during neoadjuvant treatment after the last dose of neoadjuvant treatment, during adjuvant treatment, and End of Treatment
Other outcomes:
Locations:
city: Farmington Hills
country: United States
facility: Detroit Clinical Research Center
state: Michigan
city: Canton
country: United States
facility: Aultman Hospital, Cancer Center
state: Ohio
city: Brest
country: Belarus
facility: Brest Regional Oncology Center
city: Gomel
country: Belarus
facility: Gomel Regional Clinical Oncology Center
city: Lesnoy
country: Belarus
facility: N.N. Aleksandrov Republican Research Oncology and Medical Radiology Center
city: Minsk
country: Belarus
facility: Minsk City Clinical Oncology Center
city: Mogilev
country: Belarus
facility: Mogilev Regional Oncology Center
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Oncology Center
city: Temuco
country: Chile
facility: Medical Research Limited Society
city: Viña Del Mar
country: Chile
facility: Oncocentro Apys
city: Medellín
country: Colombia
facility: Clinic Life Foundation
city: Medellín
country: Colombia
facility: Rodrigo Botero SAS
city: Batumi
country: Georgia
facility: LTD High-Tech Hospital MedCenter
city: Kutaisi
country: Georgia
facility: JSC "Evex Hospitals
city: Tbilisi
country: Georgia
facility: LTD Acad. F. Todua Medical Center - LTD Research Institute of Clinical Medicine
city: Tbilisi
country: Georgia
facility: LTD Aversi Clinic
city: Tbilisi
country: Georgia
facility: LTD Cancer Research Centre
city: Tbilisi
country: Georgia
facility: LTD Health House
city: Tbilisi
country: Georgia
facility: LTD Institute of Clinical Oncology
city: Tbilisi
country: Georgia
facility: LTD S.Khechinashvili University Hospital
city: Tbilisi
country: Georgia
facility: Malkhaz Katsiashvili Multiprofile Emergency Medicine Center
city: Bengaluru
country: India
facility: Cytecare Cancer Hospitals
city: Lucknow
country: India
facility: King George's Medical University, Department of Endocrine surgery, Shatabdi Phase II
city: Mumbai
country: India
facility: Tata Memorial Centre
city: Nagpur
country: India
facility: HCG NCHRI Cancer Centre
city: Vellore
country: India
facility: Christian Medical College, Department of Medical Oncology
city: Daegu
country: Korea, Republic of
facility: Keimyung University - Dongsan Medical Center
city: Arkhangel'sk
country: Russian Federation
facility: Arkhangelsk Clinical Oncology Center
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Oncology and Nuclear Medicine Center
city: Chelyabinsk
country: Russian Federation
facility: Evimed, LLC
city: Ivanovo
country: Russian Federation
facility: Ivanovo Regional Oncology Center
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Center
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk A.I. Kryzhanovsky Regional Oncology Center
city: Kursk
country: Russian Federation
facility: Kursk Regional Clinical Oncology Center
city: Moscow
country: Russian Federation
facility: N.N. Blokhin National Medical Oncology Research Center
city: Moscow
country: Russian Federation
facility: National Medical Research Center for Radiology
city: Moscow
country: Russian Federation
facility: Vitamed" LLC
city: Obninsk
country: Russian Federation
facility: A.F.Tsyb Medical Radiology Research Center
city: Omsk
country: Russian Federation
facility: Clinical Oncology Center
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk Interdistrict Oncology Center
city: Rostov-on-Don
country: Russian Federation
facility: Rostov Oncology Research Institute
city: Ryazan'
country: Russian Federation
facility: Regional Clinical Oncology Center
city: Saint Petersburg
country: Russian Federation
facility: AV Medical Group
city: Saint Petersburg
country: Russian Federation
facility: City Clinical Oncology Center
city: Saint Petersburg
country: Russian Federation
facility: Clinic "Mart"
city: Saint Petersburg
country: Russian Federation
facility: I.I. Mechnikov North-Western State Medical University
city: Saint Petersburg
country: Russian Federation
facility: Leningrad Regional Oncology Center (Outpatient Department)
city: Saint Petersburg
country: Russian Federation
facility: Leningrad Regional Oncology Center (Surgery Department)
city: Saint Petersburg
country: Russian Federation
facility: N.N. Petrov National Medical Research Center of Oncology
city: Saint Petersburg
country: Russian Federation
facility: Oncology Center of Moskovskiy District
city: Saint Petersburg
country: Russian Federation
facility: Private Medical Institution "EVROMEDSERVIS", Department of Oncology
city: Saint Petersburg
country: Russian Federation
facility: St. Petersburg Clinical Research and Practical Center for Specialized Types of Medical Care (Oncology)
city: Saransk
country: Russian Federation
facility: Republican Oncology Center
city: Sochi
country: Russian Federation
facility: Oncology Center #2
city: Tomsk
country: Russian Federation
facility: Tomsk National Research Medical Center
city: Veliky Novgorod
country: Russian Federation
facility: Regional Clinical Oncology Center
city: Volgograd
country: Russian Federation
facility: Volgograd Regional Clinical Oncology Center
city: Cape Town
country: South Africa
facility: GVI Oncology, Cape Gate Oncology Centre
city: Durban
country: South Africa
facility: The Oncology Centre
city: Johannesburg
country: South Africa
facility: Medical Oncology Centre of Rosebank
city: Pretoria
country: South Africa
facility: Little Company of Mary Medical Center, Department of Oncology
city: Pretoria
country: South Africa
facility: University of Pretoria, Department of Medical Oncology
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
city: Chernihiv
country: Ukraine
facility: Chernihiv Regional Oncology Center
city: Chernivtsi
country: Ukraine
facility: Chernivtsi Regional Clinical Oncology Center
city: Dnipro
country: Ukraine
facility: Clinical Oncology Center
city: Dnipro
country: Ukraine
facility: Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy
city: Ivano-Frankivsk
country: Ukraine
facility: Prikarpattia Clinical Oncology Center
city: Kharkiv
country: Ukraine
facility: Communal Non-profit enterprise "Regional Center of Oncology"
city: Kharkiv
country: Ukraine
facility: State Institution: S.P. Hryhoriev Institute of Medical Radiology under the Ukrainian Academy of Medical Sciences, Department of Clinical Oncology and Hematology
city: Khmelnytskyi
country: Ukraine
facility: Khmelnytskyi Regional Oncology Center
city: Kryvyi Rih
country: Ukraine
facility: Kryvyi Rih Oncology Center, Department of Chemotherapy
city: Kyiv
country: Ukraine
facility: Kyiv City clinical Hospital #2
city: Kyiv
country: Ukraine
facility: Kyiv Regional Oncology Center, Department of Mastology
city: Kyiv
country: Ukraine
facility: Medical Center "Verum"
city: Kyiv
country: Ukraine
facility: Medical Center of First Private Clinic
city: Luts'k
country: Ukraine
facility: Volyn Regional Oncology Center, Department of Chemotherapy
city: Lviv
country: Ukraine
facility: Public Institution under Lviv Regional Council: Lviv Regional Treatment and Diagnostics Oncology Center, Department of Chemotherapy
city: Mariupol
country: Ukraine
facility: Mariupol Oncology Center
city: Odesa
country: Ukraine
facility: Odesa Regional Clinical Hospital, Center for Mastology, Department of Thoracic Surgery
city: Odesa
country: Ukraine
facility: Odesa Regional Oncology Center
city: Ternopil'
country: Ukraine
facility: Ternopil Regional Clinical Oncology Center, Department of Chemotherapy
city: Uzhhorod
country: Ukraine
facility: Central City Clinical Hospital, Department of Oncology and Radiology
city: Uzhhorod
country: Ukraine
facility: Zakarpattia Regional Clinical Oncology Center, Department of Chemotherapy
city: Vinnytsia
country: Ukraine
facility: Podillia Regional Oncology Center
city: Zhytomyr
country: Ukraine
facility: Zhytomyr Regional Oncology Center
Study officials:
References: