Randomised, double-blind, parallel group, equivalence, multicentre phase III trial to compare the efficacy, safety and pharmacokinetics of HD201 to Herceptin® in patients with HER2+ early breast cancer

• Register: EUCTR
• Last refreshed on: 26 September 2023
• Main ID: EUCTR2016-004019-11-ES
• Date of registration: 11/04/2018
• Prospective Registration: No
• Primary sponsor: Prestige BioPharma Pte Ltd
• Public title: Randomised, double-blind, parallel group, equivalence, multicentre phase III trial to compare the efficacy, safety and pharmacokinetics of HD201 to Herceptin® in patients with HER2+ early breast cancer
• Scientific title: Randomised, double-blind, parallel group, equivalence, multicentre phase III trial to compare the efficacy, safety and pharmacokinetics of HD201 to Herceptin® in patients with HER2+ early breast cancer - Troika
• Date of first enrolment: 09/04/2018
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004019-11
• 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: yes Other specify the comparator: Herceptin 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

Belarus, Bulgaria, Czech Republic, Denmark, Estonia, France, Georgia, Germany, Hungary, Italy, Korea, Republic of, Malaysia, Netherlands, Philippines, Poland, Russian Federation, Spain, Thailand, Ukraine

Contacts

• Name: Cristina Arredondo
• Affiliation: QualitecFarma

• Name: Cristina Arredondo
• Affiliation: QualitecFarma

Key inclusion & exclusion criteria

Inclusion criteria:
1. Able and willing to give written informed consent .
2. Females = 18 years of age.
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2.
4. Known hormone receptor (oestrogen receptor and progesterone receptor) status.
5. HER2 overexpressed as assessed by o Immunhistochemistry (IHC) or o Fluorescent in site hybridisation (FISH); FISH positive is defined as FISH amplification ratio = 2.0 / number of HER2 gene copies per cell > 2 o Chromogenic in situ hybridisation (CISH positive) o Patients with IHC score 3+ or positive FISH/CISH test o Patients with IHC score 2+ must also have a positive FISH/CISH test.
6. LVEF = 50% or within the normal level of the institution, as assessed by echocardiography or MUGA scan.
7. Life expectancy > 12 weeks.
8. Adequate bone marrow function as evidenced by the following: o Absolute neutrophils count = 1,500/µL o Haemoglobin = 9 g/dL o Platelet count = 100,000/µL Up to 5% deviation is acceptable.
9. Adequate hepatic and renal function as evidenced by the following: o Creatinine clearance = 60 mL/min o Total bilirubin = 1.5 x upper limit of normal (ULN) o AST (SGOT) and ALT (SGPT) = 2.5 x ULN Up to 10% deviation is acceptable.
10. Ability to comply with the study protocol.
11. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of study treatment and agree to use effective contraception (intrauterine device, diaphragm, diaphragm with spermicide or a reliable barrier method, e.g. condom, or condom with spermicide) throughout the study period and 7 months after discontinuation of study drug.
12. Non-metastatic, unilateral, newly diagnosed, operable early breast cancer (EBC) of clinical stage II and III including inflammatory breast cancer.
o Histologically confirmed primary invasive carcinoma of the breast.
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 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 250

Exclusion criteria:
1. Metastatic (stage IV) with exception of supraclavicular nodes.
2. Bilateral Breast Cancer
3. Multicentric breast cancer
4. History of any prior invasive breast carcinoma, except for subjects with a history of ductal carcinoma in situ (DCIS) treated with surgery.
5. History of malignant neoplasms within 5 years prior to randomisation, except for curatively treated carcinoma in situ of uterine cervix, basal cell carcinoma of the skin or squamous cell carcinoma of the skin (malignant neoplasms occurring more than 5 years prior to randomisation are permitted if curatively treated with surgery only).
6. Previous history of radiation therapy, anti-neoplastic immunotherapy, chemotherapy or anti-neoplastic biotherapy (including prior HER2 directed therapy).
7. Major surgery within 2 weeks prior to randomisation
8. Serious cardiac illness that would preclude the use of trastuzumab such as: o history of documented congestive heart failure(CHF) (New York Heart Association, NYHA, class III or greater heart disease) o LVEF < 50% by echocardiography or MUGA scan o angina pectoris requiring anti-anginal medication o evidence of transmural infarction on electrocardiogram (ECG) o uncontrolled hypertension (systolic > 180 mmHg and/or diastolic > 100 mmHg) o clinically significant valvular heart disease o high-risk uncontrolled arrhythmias.
9. Serious pulmonary illness enough to cause dyspnoea at rest or requiring supplementary oxygen therapy.
10. Known history of active hepatitis B virus (HBV) and active hepatitis C virus (HCV) infection.
11. Known HIV infection by patient declaration.
12. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
13. Known hypersensitivity to the IMPs, non-IMPs or any of the ingredients or excipients of the IMPs or non-IMPs.
14. Known hypersensitivity to murine proteins.
15. Pre-existing peripheral sensory or motor neuropathy = grade 2 (as defined by NCI-CTCAE v4.03).
16. Lactating or pregnant woman. A pregnancy test is required for all women of childbearing potential including women who had menopause onset within 2 years prior to randomisation. Women of childbearing potential must agree to use contraceptive methods during the study and for 7 months after the last dose of IMP.
17. Participation in any clinical study or having taken any investigational therapy during the 1-month period immediately preceding administration of the first dose.
18. Patients unwilling to follow the study requirements.


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

Health Condition(s) or Problem(s) studied

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

Non-metastatic, unilateral, newly diagnosed, operable early breast cancer (EBC) of clinical stage II and III including inflammatory breast cancer.

Intervention(s)

Product Name: Trastuzumab
Product Code: HD201
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Current Sponsor code: HD201
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: HERCEPTIN
Product Name: Trastuzumab
Product Code: HERCEPTIN
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Current Sponsor code: HERCEPTIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: At the time of surgery after neoadjuvant treatment completion after 24 weeks.

Secondary Objective: • To compare total breast pathological complete response rate (bpCR) between the two arms at the time of surgery.
• To compare overall response rate (ORR) between the two treatment arms at the time of surgery.
• To compare event-free survival (EFS) between the two treatment arms one year after end of treatment.
• To compare overall survival (OS) between the two treatment arms one year after end of treatment.
• To compare immunogenicity of HD201 and Herceptin®.
• To compare safety and tolerability between the two treatment arms.
• To compare the PK profile of HD201 and Herceptin®.

Main Objective: The primary objective of this study is to show equivalence of the total pathological complete response rate (tpCR) in patients treated with HD201 plus chemotherapy to that in patients treated with Herceptin® plus chemotherapy. tpCR will be assessed at the time of surgery after neoadjuvant treatment completion after 24 weeks.

Primary end point(s): Total pathological complete response rate (tpCR), defined as complete absence of cancer cells in the breast and in the axillary lymph nodes (ypT0/is, ypN0) assessed in specimen obtained during surgery.

Secondary Outcome(s)

Secondary end point(s): Efficacy:
• bpCR defined as complete disappearance of cancer cells in the breast (ypT0/is) at the time of surgery.
• Overall response rate (ORR) defined as proportion of patients whose best overall response is either complete response (CR) or partial response (PR) as assessed by ultrasound and mammography and clinical examination prior to surgery.
• Overall survival (OS) defined as the time from randomisation until death from any cause.
• Event-free survival (EFS) defined as the time from randomisation until progression of disease or death from any cause.
Safety and tolerability:
• Safety and tolerability will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events and CTC v4.03
• Cardiac dysfunction will be monitored by 12-lead ECG and measurement of the LVEF by echocardiography or MUGA scan
• Vital signs
• Clinical laboratory parameters Immunogenicity: Incidence of human trastuzumab antibodies at baseline, before surgery, at end of treatment and one year after completion of trastuzumab therapy. Pharmacokinetics (and Ctrough): Sampling will be performed in all patients. At Cycle 5 (Week 12) and Cycle 8 (Week 21), samples will be taken before administration of treatment (Ctrough).

Timepoint(s) of evaluation of this end point: At the time of surgery.

Secondary ID(s)

2016-004019-11-FR

Troika-1

Source(s) of Monetary Support

Prestige BioPharma Pte Ltd

Ethics review

Status: Approved
Approval date: 14/02/2018
Contact: