A randomised, double-blind, parallel group, equivalence, multicentre phase III trial to compare the efficacy, safety and pharmakokinetics of HD201 to Herceptin® in patients with HER2+ early breast cancer
- Conditions
- on-metastatic, unilateral, newly diagnosed, operable early breast cancer (EBC) of clinical stage I-II and IIIa (T3-N0-M0) including inflammatory breast cancer.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004019-11-EE
- Lead Sponsor
- Prestige BioPharma Pte Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 500
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
- Immunhistochemistry (IHC) or
- Fluorescent in site hybridisation (FISH); FISH positive is defined as FISH amplification ratio = 2.0 / number of HER2 gene copies per cell > 2
- Patients with IHC score 3+ or positive FISH test
- Patients with IHC score 2+ must also have a positive FISH 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:
- Absolute neutrophils count = 1,500/µL
- Haemoglobin = 9 g/dL
- Platelet count = 100,000/µL
Up to 5% deviation is acceptable.
9. Adequate hepatic and renal function as evidenced by the following:
- Creatinine clearance = 60 mL/min
- Total bilirubin = 1.5 x upper limit of normal (ULN)
- 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 14 days of 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, 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 I-II and IIIa (T3-N0-M0) including inflammatory breast cancer.
- At least one measurable lesion according to RECIST criteria v1.1
- Histologically or cytologically 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
1. Metastatic (stage IV) or bilateral or multifocal/multicentric breast cancer, with exception of supraclavicular nodes.
2. History of any prior invasive breast carcinoma, except for subjects with a past history of ductal carcinoma in situ (DCIS) and/or lobular carcinoma in situ (LCIS) treated with surgery only.
3. 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).
4. Previous history of radiation therapy, immunotherapy, chemotherapy or biotherapy (including prior HER2 directed therapy).
5. Major surgery within 4 weeks prior to randomisation.
6. Serious cardiac illness that would preclude the use of trastuzumab such as:
- history of documented congestive heart failure (CHF) (New York Heart Association, NYHA, class II or greater heart disease)
- LVEF < 50% by echocardiography or MUGA scan
- angina pectoris requiring anti-anginal medication
- evidence of transmural infarction on electrocardiogram (ECG)
- uncontrolled hypertension (systolic > 180 mmHg and/or diastolic > 100 mmHg)
- clinically significant valvular heart disease
- high-risk uncontrolled arrhythmias.
7. Serious pulmonary illness enough to cause dyspnoea at rest or requiring supplementary oxygen therapy.
8. Known history of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection.
9. HIV infection. The HIV test is only to be done when clinically indicated.
10. 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.
11. Known hypersensitivity to the IMPs, non-IMPs or any of the ingredients or excipients of the IMPs or non-IMPs.
12. Known hypersensitivity to murine proteins.
13. Pre-existing peripheral sensory or motor neuropathy = grade 2 (as defined by NCI- CTCAE v4.03).
14. 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.
15. Concurrent hormonal therapy including birth control pills, ovarian hormone replacement for menopause, selective oestrogen receptor modulator (SERM) either for osteoporosis or breast cancer prevention (all those treatments should be stopped before randomization).
16. Participation in any clinical study or having taken any investigational therapy during the 1-month period immediately preceding administration of the first dose.
17. Patients unwilling to follow the study requirements
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method