E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to demonstrate equivalent PK in terms of area under the curve at steady state (AUCSS) between CT-P6 and the comparator Herceptin in patients with metastatic breast cancer. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to obtain additional comparative PK data, as well as initial safety and efficacy data with CT-P6 in comparison to Herceptin in patients with metastatic breast cancer. The PK, PD, efficacy and safety objectives are to evaluate CtroughSS, change from baseline in serum Her-2 shed antigen, ORR, cardiotoxicity, and immunogenicity of CT-P6 compared to Herceptin. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written and signed informed consent, obtained prior to starting any protocol-specific procedures. 2. Are females over 18 years of age. 3. Have pathologically confirmed, uni-dimensionally measurable metastatic breast cancer. 4. Have a strong Her-2 over-expression as described by a 3+ score by immunohistochemistry (IHC) or a positive fluorescence in-situ hybridisation (FISH) or chromogenic in-situ hybridisation (CISH) result. 5. Have target lesions outside prior radiation fields. 6. Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 7. Have at least 4 weeks since last surgery or radiation therapy, with full recovery. Patients must have received no radiotherapy for the treatment of metastatic disease. However, patients who have received adjuvant radiotherapy as part of the treatment of early breast cancer are eligible if the last fraction of radiotherapy was administered at least 6 months prior to randomisation. Radiotherapy administered for the relief of metastatic bone pain other than the sole site of measurable diseases is allowed, but: o no more than 25% of marrow-bearing bone should have been irradiated, o the last fraction of radiotherapy should not have been administered within 4 weeks prior to randomisation, o patients must have recovered from all treatment-related toxicities prior to randomisation. 8. Regarding trastuzumab treatment; o Have never been treated with trastuzumab, or o Prior trastuzumab and chemotherapy (taxane included) or trastuzumab alone as neoadjuvant/adjuvant treatment is discontinued > 12 months prior to randomisation. 9. Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of randomised therapy. Prophylactic use of bisphosphonates in patients without bone diseases is not permited, except for the treatment of osteoporosis. 10. Laboratory requirements as defined below: Haematology: Absolute neutrophil count (ANC): ≥1,500/mm EXP 3 (1.5 x 10 EXP 9 cells/L); Platelets: ≥ 100,000/mm EXP 3 (100 x 10 EXP 9 cells/L); Haemoglobin: ≥ 9.0 g/dL; Liver function: Total bilirubin: ≤ 1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤ 2.5 x ULN, or ≤ 5.0 x ULN in the case of liver metastasis; Renal function: Serum creatinine: ≤ 2 mg/dL 11. Are expected to survive for at least 6 months. 12. Are not pregnant and do not plan to become pregnant during the study. For females of childbearing potential, pregnancy tests must be performed via serum pregnancy test at baseline (within 7 days prior to starting study drug) and at the end of treatment. Further tests are only required if there is a suspicion of pregnancy. If sexually active, must be using at least one reliable method of contraception (e.g., a barrier method [condom or occlusive cap] with spermicidal foam/gel/film/cream/suppository, an intrauterine device [IUD] or intrauterine system [IUS], oral or injectable contraception, sterilisation of sole male partner, abstinence) throughout the study period and for 6 months after the last study drug treatment. Non-childbearing potential is defined as: - aged ≥50 years and naturally amenorrhoeic for at least 1 year*, or - premature ovarian failure confirmed by a specialist gynaecologist, or - previous bilateral salpingo-oophorectomy or hysterectomy, or - XY genotype, Turner’s syndrome, uterine agenesis. * Amenorrhoea following cancer therapy does not rule out childbearing potential. |
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E.4 | Principal exclusion criteria |
1. Have received prior chemotherapy for metastatic breast cancer. 2. Current clinical or radiographic evidence of central nervous system (CNS) metastases. A computerised tomography (CT) or magnetic resonance imaging (MRI) scan of the brain is mandatory in cases of clinical suspicion of brain metastases within 21 days of randomisation. Eligible patients must be asymptomatic and cannot be receiving steroids. 3. Are receiving concurrent immunotherapy or hormonal therapy. 4. Have a history of congestive heart failure (CHF) of any New York Heart Association (NYHA) criterion, or serious cardiac arrhythmia requiring treatment (except for atrial fibrillation and/or paroxysmal supraventricular tachycardia). 5. Have an abnormal LVEF (≤50%) at baseline, as determined by either two-dimensional echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan. If the patient is randomised, the same method of LVEF assessment, ECHO or MUGA, must be used throughout the study. 6. History of myocardial infarction within 6 months before randomisation. 7. Current uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or unstable angina. 8. Have severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy. 9. Have had a prior malignancy within the last 5 years that might affect breast cancer diagnosis or assessment. 10. Have had prior mediastinal irradiation (except internal mammary-node irradiation for the present breast cancer). 11. Have received cumulative doses of anthracycline exceeding 360 mg/m2 of body surface area for doxorubicin, 720 mg/m2 for epirubicin, 120 mg/m2 for mitoxantrone, 90 mg/m2 for idarubicin, or the equivalent of 360 mg/m2 of doxorubicin for other anthracyclines such as liposomal doxorubicin. If more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 360 mg/m2 of doxorubicin. 12. Have a history of hypersensitivity to the trastuzumab or to drugs with similar chemical structures, or to any of the excipients, or to murine proteins. 13. Have a history of severe hypersensitivity reaction to paclitaxel, or to any of the excipients. 14. Have peripheral neuropathy of grade 2 or greater 15. Have active or uncontrolled infection 16. Have any other medical or psychiatric condition that could compromise study participation. 17. Have received treatment with any other investigational drug in the last 30 days before study entry, or within less than five half-lives after receiving the previous investigational drug 18. Current known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). 19. Are pregnant or a nursing mother. 20. Have a history or suspicion of unreliability, poor cooperation or non-compliance with medical treatment. 21. Have any concurrent disease or condition that, in the opinion of the investigator, would make the patient unsuitable for participation in the study. 22. Have previously been randomised in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetic Analysis: The primary PK endpoint will be the AUCss following steady state. AUCss is defined as the AUC at steady state. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The primary endpoint will be reached at 6 months (8 treatment cycles), although treatment will continue until disease progression, death, or discontinuation. After the primary endpoint is reached, all patients will be followed-up until Independent Tumour Response Committee (ITRC)-determined progression (or death), even if study drug treatment has been discontinued due to investigator-determined progression or unacceptable toxicity. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |