A Phase 3 Study to Compare the Efficacy and Safety of CT-P6 and Herceptin as Neoadjuvant and Adjuvant Treatment in Patients with HER2-Positive Early Breast Cancer

• Register: EUCTR
• Last refreshed on: 7 January 2019
• Main ID: EUCTR2013-004525-84-LV
• Date of registration: 19/02/2014
• Prospective Registration: Yes
• Primary sponsor: CELLTRION, Inc.
• Public title: A Phase 3 Study to Compare the Efficacy and Safety of CT-P6 and Herceptin as Neoadjuvant and Adjuvant Treatment in Patients with HER2-Positive Early Breast Cancer
• Scientific title: A Phase 3, Double-Blind, Randomized, Parallel-Group, Active-Controlled Study to Compare the Efficacy and Safety of CT-P6 and Herceptin as Neoadjuvant and Adjuvant Treatment in Patients with HER2-Positive Early Breast Cancer
• Date of first enrolment: 03/04/2014
• Target sample size: 532
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004525-84
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belarus, Brazil, Chile, Croatia, France, Georgia, Greece, Hungary, India, Italy, Korea, Republic of, Latvia, Mexico, Netherlands, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Serbia, South Africa, Spain, Ukraine, United States

Contacts

• Name: Ho Ung Kim
• Affiliation: CELLTRION, Inc.

• Name: Ho Ung Kim
• Affiliation: CELLTRION, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Each patient must meet all of the following criteria to be enrolled in this study:
1.Patient is a female 18 years of age or older.
2.Patient who has Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
3.Patient who has histologically confirmed and newly diagnosed breast cancer.
4.Patient who has clinical stage I, II, or IIIa operable breast cancer according to the AJCC Breast Cancer Staging 7th edition.
5.At least one measurable lesion by Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
a.Tumor lesions: =10 mm in long axis by computerized tomography (CT) scan
b.Malignant lymph nodes: =15 mm in short axis when assessed by CT scan
6.Patient who has HER2 positive status confirmed locally, defined as 3 + score by immunohistochemistry (IHC). When the IHC result is equivocal (defined as 2 + score), patient who has a positive fluorescence in situ hybridization (FISH) or a chromogenic in situ hybridization (CISH) result.
7.Patient who has a normal LVEF (=55%) at Baseline, as determined by either two-dimensional echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan. If the patient is randomized, the same method of LVEF assessment, ECHO or MUGA, must be used throughout the study.
8.Patient who has known estrogen receptor and progesterone receptor status tested at Screening.
9.Patient who has adequate bone marrow function, defined as:
a.Absolute neutrophil count =1,500/µL
b.Hemoglobin =10.0 g/dL
c.Platelets =100,000/µL
10.Patient who has adequate hepatic and renal function, defined as:
a.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × upper limit of normal (ULN)
b.Total bilirubin =1.5 × ULN
c.Alkaline phosphatase =2.5 × ULN
d.Serum creatinine =1.5 mg/dL
11.Patient who has the ability to comprehend the full nature and purpose of the study, including possible risks and side effects, to cooperate with the investigator, to understand verbal and/or written instructions, and to comply with the requirements of the entire study.
12.Patient must voluntarily sign an Institutional Review Board/Independent Ethics Committee (IRB/IEC)-approved informed consent form (ICF) before any study specific procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 132

Exclusion criteria:
Patients meeting any of the following criteria will be excluded from the study:
1.Patient who has bilateral breast cancer.
2.Patient who is pregnant or lactating.
3.Patient who has received prior treatment for breast cancer, including chemotherapy, biologic therapy, hormone therapy, immunotherapy, radiation, or surgery, with the exception of diagnostic biopsy for primary breast cancer.
4.Patient who has received any prior therapy with anthracyclines.
5.Patient who has other concomitant active malignancy or history of malignancy in the past 5 years except treated basal cell carcinoma of the skin or carcinoma in situ of the cervix.
6.Serious cardiac illness or medical conditions that could preclude the use of trastuzumab, specifically: New York Heart Association (NYHA) class =2, history of documented congestive heart failure (CHF), high-risk uncontrolled arrhythmias, angina pectoris requiring medication, clinically significant valvular disease, evidence of transmural infarction on electrocardiogram (ECG), poorly controlled hypertension.
7.Patient who has a current history of infection with hepatitis B, hepatitis C, or infection with human immunodeficiency virus, or who has a positive result to the screening test for those infections.
8.Patient who has had any recent infection requiring a course of systemic anti infectives that were completed =14 days before randomization (with the exception of uncomplicated urinary tract infection).
9.Patient who is a woman of childbearing potential who is not consenting to use highly effective methods of birth control (e.g., intra-uterine device, barrier methods including condom and diaphragm, also in conjunction with spermicidal jelly, or total abstinence; Oral, injectable, or implant hormonal contraceptives are not acceptable) during treatment and for an additional 6 months after the last administration of the protocol specified treatment.
10.Patient who is currently receiving treatment with another investigational device or medical product, or less than 30 days or 5 half-lives, whichever is longer, have spanned since ending treatment with another investigational device or medical product.
11.Patient who has known sensitivity to any of the products to be administered during the study, including mammalian cell derived drug products, trastuzumab, and murine proteins, or to any of the excipients.
12.Patient who has previously participated in this study.
13.Patient who will likely not be available to complete all protocol required study visits or procedures.
14.Patient who has history or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Her-2 Positive Early Breast Cancer
MedDRA version: 16.1 Level: PT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: CT-P6 (trastuzumab)
Product Code: CT-P6
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Current Sponsor code: CT-P6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 440-

Trade Name: HERCEPTIN® [trastuzumab]
Product Name: Herceptin [trastuzumab]
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 440-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: The pCR will be determined at the time of surgery, using hematoxylin and eosin evaluation of the resected breast specimen.

Secondary Objective: The secondary objectives of this study are to evaluate additional efficacy parameters (overall response rate, disease-free survival, progression-free survival, overall survival, breast conservation rate, and other pCRs) and to obtain additional PK, pharmacodynamic, safety, and biomarker data.

Main Objective: The primary objective of this study is to demonstrate equivalence of CT-P6 and Herceptin, both given in combination with docetaxel (75 mg/m2, Cycles 1 to 4) followed by FEC (5-fluorouracil 500 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2,, Cycles 5 to 8), in terms of efficacy as determined by pathological complete response (pCR), in patients with HER2-positive operable early breast cancer.

Primary end point(s): The primary efficacy endpoint will be the pCR, defined as the absence of invasive tumor cells in the breast and in axillary lymph nodes, regardless of DCIS.

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoints will be the following:
•ORR (clinical response rate and radiological response rate), defined as CR or PR as assessed by RECIST Version 1.1 (Appendix 12.2) (Eisenhauer et al 2009)
•DFS, measured from the time of occurrence of attained CR to disease recurrence or death as a result of any cause
•PFS, measured from the randomization to disease recurrence, progression or death from any cause
•OS, defined as time from randomization to death from any cause
•Breast conservation rate, measured as the proportion of patients who undergo breast conservation surgery
•Other pCRs
•pCRB
•pCR of breast and axillary nodes with absence of DCIS

The secondary PK endpoints during the Neoadjuvant Period will be the following:
•Observed maximum serum concentration after administration (Cmax), at each dose
•Observed trough serum concentration (Ctrough), prior to next dose for Cycle 1 to Cycle 7, and at EOT1 for dose 8.

The secondary pharmacodynamic endpoint is serum HER2 shed antigen during the Neoadjuvant Period

The secondary safety endpoints will be the following:
•Incidence and severity of AEs, including SAEs graded according to the NCI CTCAE Version 4.03.
•Cardiotoxicity, as assessed by mean change from Baseline to endpoint assessment in LVEF.
•Immunogenicity, as assessed by the incidence of antidrug antibody.

Biomarker Endpoints (Optional):
The Fc?R genotype (Fc?RIIa, IIIa, and/or any necessary genotypes) will be evaluated as secondary endpoints.

Timepoint(s) of evaluation of this end point: see protocol table 12.1

Secondary ID(s)

CT-P6-3.2

Source(s) of Monetary Support

CELLTRION, Inc