E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine if HER2 positive primary breast cancer can be detected by [89Zr]trastuzumab PET/CT imaging, using histopathological examination as the gold standard, after neoadjuvant treatment.
- Assess the negative predictive value and sensitivity of [89Zr]trastuzumab PET/CT imaging to detect HER2 positive primary breast cancer.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives:
- Assess agreement between the [89Zr]trastuzumab PET/CT-imaging signal in the tumor and axilla, histopathologic evidence of tumor and HER2 expression.
- Assess the agreement between different imaging modalities ([89Zr]trastuzumab PET/CT-scan, [18F]FDG-PET/CT and MRI).
Research aims to assess primary objective - Evaluation of the surgical specimen.
- Determine the feasibility to image HER2 positive primary breast cancer using preoperatively PET/CT imaging and a HER2 targeting tracer.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Female patients aged 18 years or older.
• Confirmed diagnosis of HER2 positive primary breast cancer (confirmed by immunohistochemical staining of preoperative core-needle biopsy of tumor tissue; IHC with strong intensity 3+ or fluorescence in situ hybridization (FISH)) and eligible for breast cancer surgery.
• Tumor size ≥ 5 mm (0.5 cm) diameter according to anatomical imaging data.
• WHO performance score 0-2.
• Patients planned for neoadjuvant therapy.
• Female patients need to be either surgically sterile, post-menopausal or pre-menopausal and not pregnant. Pre-menopausal female patients who are not surgically sterile should also employ an effective method of birth control for at least one month post-dosing when it consists of a hormonal contraceptive method or IUD. For other contraceptive methods, premenopausal females who are not surgically sterile have to agree to use an effective method of contraception.
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.
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E.4 | Principal exclusion criteria |
• Any condition that in the opinion of the investigator could potentially jeopardize the health status of the patient.
• Medical or psychiatric conditions that compromise the patient’s ability to give informed consent. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
• No metastasis or multifocal lesions.
• Prior radiotherapy to the thorax.
• Breast prosthesis in the target breast.
• Unacceptable known (clinical significant) cardiovascular or pulmonary disease, renal or liver dysfunction.
• Known hypersensitivity to drugs comparative to trastuzumab or drugs in the same class (immunoglobulins), or any of their excipients or to any component of [89Zr]trastuzumab.
• Concomitant medication known to interact with trastuzumab.
• Inability to undergo PET/CT scanning (e.g. claustrophobia, weight limits or inability to tolerate lying for the duration of an PET/CT scan (~60 min)).
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E.5 End points |
E.5.1 | Primary end point(s) |
- Quantification of the accumulation of [89Zr]trastuzumab (by using SUV and/or RUV) in the primary tumor on PET/CT imaging. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After HER2+ PET/CT imaging. |
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E.5.2 | Secondary end point(s) |
- Assess agreement between PET/CT-imaging signal in the tumor and axilla, histopathologic evidence of tumor and HER2 expression. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After HER2+ PET/CT imaging and pathology assessment. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | 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) | 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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.1.7 | Other | No |
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 | 2 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |