E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HER2-positive metastatic breast cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
1. The primary objective is to evaluate the patient’s preference for either the subcutaneous (SC) or the intravenous (IV) route of administration of trastuzumab in treatment of HER2-positive mBC patients responding to a first line treatment for more than 3 years |
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E.2.2 | Secondary objectives of the trial |
•To assess the safety and tolerability of trastuzumab administered subcutaneously
•To assess the health care professional (HCP) experience and preference for either the SC or the IV route of administration of trastuzumab
•Quality of life (QoL)
•To assess efficacy (progression-free survival and overall survival data)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Female and male patients aged ≥ 18 years
2.Signed informed consent prior to any study specific procedure
3.Able and willing to comply with protocol
4.ECOG performance status 0–2
5.Hormonal therapy will be allowed as per institutional guidelines
6.Prior use of anti-HER2 therapy will be allowed
7.LVEF of ≥ 50% measured by ECHO or MUGA scan prior to first dose of trastuzumab, documented results within an acceptable limit from a cardiac assessment within 3 months prior to enrolment
8.HER2-positive disease IHC3+ or ISH positive as determined in a local laboratory that is experienced/certified in HER2-expression testing using an accurate and validated assay, or documented HER2 status, as the patients in this study are long responders
9.Histologically or cytologically confirmed locally advanced or mBC with at least one measurable lesion
10.Documented history of histologically or cytologically confirmed mBC
11.mBC patients on treatment with first line trastuzumab IV free of disease progression for at least 3 years (confirmed by standard local procedures according to disease history and standard practice)
12.Patient registered with or beneficiary from social security system
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E.4 | Principal exclusion criteria |
1.History of other malignancy which could affect compliance with the protocol or interpretation of results. Patients with curatively treated carcinoma in situ of the cervix or basal cell carcinoma, and patients with other curatively treated malignancies who have been disease-free for at least 5 years, are eligible. Patients with previous DCIS of the breast are also eligible for the study
2.Patients with severe dyspnea at rest or requiring supplementary oxygen therapy
3.Patients with other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
4.Serious cardiac illness or medical conditions that would preclude the use of trastuzumab, specifically: history of documented CHF, high-risk uncontrolled arrhythmias, angina pectoris requiring medication , clinically significant valvular disease, evidence of transmural infarction on ECG, diagnosed poorly controlled hypertension
5.Known infection with human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV)
6.Pregnant or lactating women. Positive serum pregnancy test in women of childbearing potential, premenopausal or less than 12 months of amenorrhea post-menopause, within 7 days prior to the first dose of study drug
7.Women of childbearing potential, premenopausal or less than 12 months of amenorrhea post-menopause (unless surgically sterile) and male patients with partners of childbearing potential who are unable or unwilling to use adequate contraceptive measures during study treatment. In this study, menopause is defined as a minimum of 12 consecutive months of amenorrhea during which time no other biological or physiological cause had been identified as a potential cause of this state. Examples of adequate contraceptive measures are intrauterine device, barrier method (condoms, diaphragm) also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not acceptable
8.Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment, including hormonal therapy, bisphosphonate therapy and immunotherapy, within 28 days prior to the first dose of study treatment
9.Known hypersensitivity to trastuzumab, murine proteins, to any of the excipients of Herceptin®, or the adhesive of the subcutaneous device, or a history of severe allergic or immunological reactions, e.g. difficult to control asthma
10.Patients assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol
11.Radiographic evidence of central nervous system (CNS) metastases as assessed by computed tomography (CT) or magnetic resonance imaging (MRI), unless they have been treated and have been stable for at least 3 months
12.Inadequate organ function, evidenced by the following laboratory results:
a)Absolute neutrophil count < 1,500 cells/mm3
b)Platelet count < 100,000 cells/mm3
c)Hemoglobin < 9 g/dL
d)Total bilirubin > 1.5 × ULN (unless the patient has documented Gilbert’s syndrome)
e)AST (SGOT) or ALT (SGPT) > 2.5 × ULN ( > 5 × ULN in patients with liver metastases)
f)Alkaline phosphatase levels > 2.5 × the ULN ( > 5 × ULN in patients with liver metastases, or > 10 × ULN in patients with bone metastases)
g)Serum creatinine > 2.0 mg/dL or 177 μmol/L
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E.5 End points |
E.5.1 | Primary end point(s) |
Patient preference for SC Trastuzumab versus IV Trastuzumab administration |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After completing the cross over period (6 cycles) |
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E.5.2 | Secondary end point(s) |
•To assess the safety and tolerability of trastuzumab administered subcutaneously
•To assess the health care professional (HCP) experience and preference for either the SC or the IV route of administration of trastuzumab
•Quality of life (QoL)
•To assess efficacy (progression-free survival and overall survival data)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After completing the cross over period or end of study |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.1.1 | First administration to humans | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 100 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |