E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with primary HER2 positive early or locally advanced breast cancer, who received the IP (SB3 or Herceptin®) in the SB3-G31-BC trial. |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10072740 |
E.1.2 | Term | Locally advanced breast cancer |
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 |
The primary objective is to observe the incidence of symptomatic congestive heart failure (CHF) New York Heart Association (NYHA) class II,III and IV and asymptomatic left ventricular ejection fraction (LVEF) decrease in subjects who participated in the SB3-G31-BC Study and treated with SB3 ( proposed trastuzumab biosimilar) or Herceptin® as neoadjuvant and adjuvant treatment. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
To observe the incidence of cardiac death and other significant cardiac conditions
To observe the long term efficacy of SB3 compared to Herceptin® by
- Event-free survival and disease-free survival (DFS)
- Overall Survival (OS) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[Cardiac Safety and Survival Cohort]
Subjects must meet all of the following criteria to be eligible for the study:
1. Subjects who have completed the study treatment of SB3-G31-BC trial according to the protocol.
2. Subjects must provide informed consent.
[Survival Only Cohort]
Inclusion criteria
Subjects must meet all of the following criteria to be eligible for the study:
1. Subjects who received SB3 or Herceptin® according to the clinical trial SB3-G31-BC.
2. Subjects who provide informed consent. If prospective data collection is not possible (e.g. when the subject is deceased or lost to follow-up), a waiver of informed consent/authorization will be requested for the retrospective data collection from medical records, where applicable and in accordance with national regulations and local ethics. If ICF waiver for the deceased subject is not allowed, their next-of-kin (if applicable) will be informed accordingly, and will be asked to give their consent where applicable and approved by IRB/IEC and in accordance with national regulations. |
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E.4 | Principal exclusion criteria |
[Cardiac Safety and Survival Cohort]:
Subjects unwilling to follow the study requirements are not eligible for the study.
[Survival Only Cohort]:
There is no exclusion criteria for the Survival Only Cohort. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The incidence of symptomatic congestive heart failure (CHF) and asymptomatic significant LVEF decrease
-CHF, defined as NYHA II, III, IV, confirmed by a cardiologist, accompanied by a significant LVEF decrease.
-Significant LVEF decrease, defined as an absolute decline of at least 10 % points from baseline LVEF (LVEF at screening of the SB3-G31-BC trial) and resulting LVEF less than 50%
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All analysis will be performed periodically and at the end of the study |
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E.5.2 | Secondary end point(s) |
1. The incidence of cardiac death and other significant cardiac conditions
-Cardiac death, defined as death definitely as a result of heart failure, myocardial infarction, or documented arrhythmia or as probable cardiac death within 24 hours of a cardiac event.
2. Event-free survival (EFS), defined as the time from the date of randomisation for SB3-G31- BC trial to the date where an event occurs. An event is breast cancer recurrence or progression (local, regional, distant or contralateral) or death due to any cause.
3. DFS, defined as the time from the date of surgery for the SB3-G31-BC trial to the date where an event occurs. An event is breast cancer recurrence (local, regional, distant, or contralateral) or death due to any cause.
4. Overall survival (OS), defined as the time from the date of randomisation for the SB3-G31-BC trial to the date of death, regardless of the cause of death. Subjects who were alive at the time of analysis will be censored at the date of the last follow up assessment.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All analysis will be performed periodically and at the end of the 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 | No |
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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Follow up study - NO IMP will be administered |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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 | 58 |
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 | No |
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 |
Bosnia and Herzegovina |
India |
Korea, Republic of |
Philippines |
Russian Federation |
Ukraine |
Vietnam |
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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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The study will close at 5 years after the last subject has received the last IP (SB3 or Herceptin®) in the setting of clinical trial SB3-G31-BC. |
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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 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
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 |