Trial to Compare the Safety, Efficacy and Immunogenicity... | NCT03556358

NCT03556358

Status Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
TX05 (trastuzumab)	Experimental	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles	Biological: TX05 (trastuzumab) Drug: Paclitaxel Drug: Epirubicin Drug: Cyclophosphamide
Herceptin®	Active Comparator	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV Herceptin 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles	Biological: Herceptin® Drug: Paclitaxel Drug: Epirubicin Drug: Cyclophosphamide

Name	Type	Description	Arm Group Labels	Other Names
TX05 (trastuzumab)	Biological	8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8)	TX05 (trastuzumab)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Proportion of Subjects in Each Treatment Arm Who Achieve Pathologic Complete Response (pCR)	Pathologic complete response was determined by central review and defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled lymph nodes following neoadjuvant systemic therapy (ypT0/Tis ypN0).	3-7 weeks following last dose of study treatment

Secondary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR)	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (ORR) = CR + PR.	End of Treatment (Week 24) or Early Termination Visit

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Histologically confirmed HER 2 overexpressing invasive primary operable Stage II/IIIa breast cancer (AJCC version 7 staging criteria).
Available tumor tissue for central review of HER2 status.
Planned surgical resection of breast tumor.
Planned neoadjuvant chemotherapy.
Documentation of HER2 gene amplification or overexpression.
Ipsilateral, measurable tumor longest diameter > 2 cm.
Known estrogen receptor (ER) and progesterone receptor (PR) hormone status (may be performed during screening).
ECOG performance status of 0 or 1.
Adequate bone marrow, hepatic and renal functions.
Left ventricular ejection fraction (LVEF) ≥ 50% or within institutional normal limits, measured by echocardiography or MUGA scan.
Effective contraception as defined by protocol.

Key Exclusion Criteria:

Investigational therapy within 2 months of first dose of study drug.
Bilateral breast cancer.
Inflammatory breast cancer
Metastases.
Prior chemotherapy, biologic therapy, radiation or surgery for any active malignancy, including breast cancer.
Cardiac insufficiency, myocardial infarction, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident, unstable angina pectoris, uncontrolled arrhythmia or pulmonary embolus within the previous 12 months prior to 1st administration of study drug.
Clinically significant active infection, poorly controlled diabetes mellitus and/or uncontrolled hypertension.
Major surgery, significant traumatic injury, radiation therapy and/or grade 3 hemorrhage within 4 weeks of 1st administration of study drug.
Pre-existing clinically significant Grade 2 peripheral neuropathy.
Malignancy within the last 5 years (except squamous/basal cell carcinoma of the skin, cervical carcinoma in situ and superficial bladder cancer).
Severe dyspnea at rest requiring oxygen therapy.
Known positive HIV, acute or chronic active infection with Hepatitis B or Hepatitis C.
Current pregnancy or breastfeeding.
Pre-existing thyroid abnormality with thyroid function that cannot be maintained in normal range despite optimal therapy.

Name	Affiliation	Role
Bonnie Mills, PhD	Tanvex BioPharma USA, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Tanvex Investigational Site 1008		Lyasny	Minsk Oblast	223040	Belarus
Tanvex Investigational Site 1007

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	TX05 (Trastuzumab)	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles TX05 (trastuzumab): 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 30, 2017	Oct 28, 2021

Arm/Group Information

ID	Title	Description
BG000	TX05 (Trastuzumab)	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles TX05 (trastuzumab): 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)
BG001	Herceptin®	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV Herceptin 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles Herceptin®: 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00054.2± 11.80 BG00153.4± 10.83 BG00253.8± 11.32

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000394 BG001400 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00069 BG00171 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG00015 BG00114 BG002

Hormone Receptor Status

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Positive	BG000253 BG001254 BG002

ECOG

Grade 0: Fully active, able to carry on all pre-disease activities without restriction

Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature.

Grade 2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.

Grade 3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.

Grade 4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.

Grade 5: Dead

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Grade 0	BG000316 BG001

Tumor Stage

Enrolled subjects should have Stage II/IIIa breast cancer.
Stage will be determined by the American Joint Committee on Cancer (AJCC) TNM (tumor size, lymph node involvement, metastasis to distant sites) staging system.
A low grade number (grade 1) usually means the cancer is slower-growing and less likely to spread. A high grade number (grade 3) means a faster-growing cancer that's more likely to spread. An intermediate grade number (grade 2) means the cancer is growing faster than a grade 1 cancer but slower than a grade 3 cancer.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
IIA	BG000142 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Proportion of Subjects in Each Treatment Arm Who Achieve Pathologic Complete Response (pCR)

Pathologic complete response was determined by central review and defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled lymph nodes following neoadjuvant systemic therapy (ypT0/Tis ypN0).

Per Protocol Population [includes all subjects who received at least one dose of study drug (TX05 or Herceptin) and had no major protocol deviations that impact the efficacy endpoints].

Posted

Number

participants

3-7 weeks following last dose of study treatment

ID	Title	Description
OG000	TX05 (Trastuzumab)	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles TX05 (trastuzumab): 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)
OG001	Herceptin®	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV Herceptin 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles Herceptin®: 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)

Units	Counts
Participants	OG000336 OG001338

Title

Denominators

Categories

Subjects who do not Meet pCR Criteria

Title	Measurements
	OG000172 OG001185

Subjects Meeting pCR Criteria

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Risk Ratio (RR)	1.0783			2-Sided	95	0.9185	1.2659					Equivalence	Two one-sided hypothesis tests were performed for pCR in order to show that TX05 is equivalent to Herceptin: TEST 1: H0a: θ1 / θ2 > 1.325 vs. H1a: θ1 / θ2 < 1.325 TEST 2: H0b: θ1 / θ2 < 0.755 vs. H1b: θ1 / θ2 > 0.755 Where θ1 is the proportion of pCR for subjects randomized to TX05 group, θ2 is the proportion of pCR for subjects randomized to Herceptin. Equivalence was concluded if the 95% CI of the risk ratio is completely contained within the pre-defined interval [0.755, 1.325].

Secondary

Objective Response Rate (ORR)

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (ORR) = CR + PR.

This analysis was performed on the modified intent-to-treat population. The modified intent-to-treat (mITT) population includes all subjects who were randomized and received at least 1 dose of TX05 or Herceptin.

Posted

Count of Participants

Participants

End of Treatment (Week 24) or Early Termination Visit

ID	Title	Description
OG000	TX05 (Trastuzumab)	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles TX05 (trastuzumab): 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)
OG001	Herceptin®	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV Herceptin 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles Herceptin®: 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	TX05 (Trastuzumab)	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles TX05 (trastuzumab): 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)	0	394	11	394	246	394
EG001	Herceptin®	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV Herceptin 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles Herceptin®: 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)	1	400	9	400	250	400

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 23.1	Systematic Assessment	EG0002 affected394 at risk EG0010 affected400 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected394 at risk EG0011 affected400 at risk
Intervertebral Disc Protrusion	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected394 at risk EG0010 affected400 at risk
Diabetic Metabolic Decompensation	Metabolism and nutrition disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected394 at risk EG0010 affected400 at risk
Vaginal Hemorrhage	Reproductive system and breast disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected394 at risk EG0010 affected400 at risk
Acute Kidney Injury	Renal and urinary disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected394 at risk EG0012 affected400 at risk
Gastrointestinal Inflammation	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected394 at risk EG0011 affected400 at risk
Multiple Organ Dysfunction Syndrome	General disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected394 at risk EG0011 affected400 at risk
Anaphylactic Reaction	Immune system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected394 at risk EG0011 affected400 at risk
Post Procedural Hemorrhage	Injury, poisoning and procedural complications	MedDRA 23.1	Systematic Assessment	EG0000 affected394 at risk EG0011 affected400 at risk
Ischemic Stroke	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected394 at risk EG0011 affected400 at risk
Fetal Death	Pregnancy, puerperium and perinatal conditions	MedDRA 23.1	Systematic Assessment	EG0000 affected394 at risk EG0011 affected400 at risk
Thrombophlebitis	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected394 at risk EG0010 affected400 at risk
Deep Vein Thrombosis	Vascular disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected394 at risk EG0011 affected400 at risk
Pneumonia	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0001 affected394 at risk EG0011 affected400 at risk
Urinary Tract Infection	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0002 affected394 at risk EG0010 affected400 at risk
COVID-19 Pneumonia	Infections and infestations	MedDRA 23.1	Systematic Assessment	EG0000 affected394 at risk EG0011 affected400 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected394 at risk EG0011 affected400 at risk
Cardiac Failure Acute	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0001 affected394 at risk EG0010 affected400 at risk
Cardiotoxicity	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected394 at risk EG0011 affected400 at risk
Myocardial Infarction	Cardiac disorders	MedDRA 23.1	Systematic Assessment	EG0000 affected394 at risk EG0011 affected400 at risk
Neutrophil Count Decreased	Investigations	MedDRA 23.1	Systematic Assessment	EG0001 affected394 at risk EG0011 affected400 at risk
Ejection Fraction Decreased	Investigations	MedDRA 23.1	Systematic Assessment	EG0000 affected394 at risk EG0011 affected400 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG00050 affected394 at risk EG00142 affected400 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 23.1	Systematic Assessment	EG00045 affected394 at risk EG00139 affected400 at risk
Peripheral Sensory Neuropathy	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG00033 affected394 at risk EG00130 affected400 at risk
Neuropathy Peripheral	Nervous system disorders	MedDRA 23.1	Systematic Assessment	EG00016 affected394 at risk EG00133 affected400 at risk
Nausea	Gastrointestinal disorders	MedDRA 23.1	Systematic Assessment	EG00027 affected394 at risk EG00131 affected400 at risk
Asthenia	General disorders	MedDRA 23.1	Systematic Assessment	EG00030 affected394 at risk EG00140 affected400 at risk
Alanine Aminotransferase Increased	Investigations	MedDRA 23.1	Systematic Assessment	EG00027 affected394 at risk EG00126 affected400 at risk
Aspartate Aminotransferase Increased	Investigations	MedDRA 23.1	Systematic Assessment	EG00019 affected394 at risk EG00112 affected400 at risk
Anemia	Blood and lymphatic system disorders	MedDRA 23.1	Systematic Assessment	EG00026 affected394 at risk EG00125 affected400 at risk

Ancestor Terms

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D004317	Doxorubicin
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D011083	Polycyclic Compounds
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D063088	Phosphoramides
D009943	Organophosphorus Compounds

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D000068878	Trastuzumab
D017239	Paclitaxel
D015251	Epirubicin
D003520	Cyclophosphamide