E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Breast cancer. |
Borstkanker. |
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E.1.1.1 | Medical condition in easily understood language |
Breast cancer. |
Borstkanker. |
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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 whether [18F]FES PET/CT improves staging for women with clinical stage II/III or LRR, grade 1-2, ER+ breast cancer as compared to standard [18F]FDG PET/CT. |
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E.2.2 | Secondary objectives of the trial |
1) To compare [18F]FDG- and [18F]FES PET imaging outcomes to clinicopathological parameters
- Standard parameters: size, location of lesion, histological subtype, grade,
ER/PR/HER2 expression levels, Ki67%/mitotic index
- Experimental parameters: intensity of ER staining, tumor cell and microvessel density, infiltration of
lymphocytes, amount of necrosis and stroma, expression of glucose transporter-1 (GLUT1) of
the primary tumor, lymph node and distant metastases
2) To obtain evidence for initiating a larger clinical trial to define the added value of [18F]FES PET/CT
for staging patients with ER+, clinically LABC and/or LRR breast cancer.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Clinical stage II/III or LRR breast cancer (all histological types) with ER+ and low grade according to Bloom Richardson criteria (grade 1-2)
- Females aged 18 years or older at screening
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
- Candidates for treatment with curative intent (patients are also allowed for inclusion in the current study if they have undergone recent surgery (<6
weeks) for current breast cancer and require staging because of unexpected stage III disease)
- [18F]FDG PET/CT imaging should be performed for staging according to standard of care (in case [18F]FDG PET/CT imaging has already been performed, patients can be included ≤21 days after this scan)
- Estimated glomerular filtration rate (eGFR) ≥30 ml/min
- Written and signed informed consent |
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E.4 | Principal exclusion criteria |
- History with another cancer within the last 5 years, except non-melanoma skin cancer
- Undergoing treatment for current breast cancer such as (neo)adjuvant chemotherapy, hormonal therapy (only in case of Tamoxifen), radiotherapy or investigational drug therapy
- Pregnancy or lactating women
- Any medical, psychological or social condition that may interfere with the subject’s safety and participation in the study, will lead to exclusion from this study
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Percentage of patients with a correctly changed treatment plan according to information obtained with [18F]FES PET/CT compared to [18F]FDG PET/CT at staging.
2) Percentage of metastatic lesions detected with [18F]FES PET/CT compared to [18F]FDG PET/CT at staging.
3) Percentage of missed metastases with [18F]FES PET/CT compared to [18F]FDG PET/CT (at staging and developed during follow-up).
4) Percentage of correct treatment plans as well as diagnostic confidence after 6 months of follow-up as determined by the adjudication committee based on the added information obtained with [18F]FES PET/CT compared to [18F]FDG PET/CT. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The endpoints will be evaluated during the follow-up. The standard follow-up will take place every 3 months for a time period of 24 months after diagnosis to detect potentially missed metastases. At 6 months of follow-up, the treatment plan will be evaluated by an independent committee (surgeon, medical oncologist and nuclear physician/radiologist). |
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E.5.2 | Secondary end point(s) |
1) The relationship between the level of [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases and standard (size, location of lesion, histological subtype, grade, ER/PR/HER2 expression levels, Ki67%/mitotic index)/experimental clinicopathological parameters (intensity of ER staining, tumor cell and microvessel density, infiltration of lymphocytes, amount of necrosis and stroma, expression of glucose
transporter-1 (GLUT1) of the primary tumor, lymph node and distant metastases).
2) Cut off value for [18F]FDG SUV (max and peak) below which [18F]FES PET/CT adds information for staging.
3) Cut off value for grade and ER expression level below which or above which, respectively, [18F]FES PET/CT adds information for staging.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The endpoints will be evaluated during the follow-up. The standard follow-up will take place every 3 months for a time period of 24 months after diagnosis to detect potentially missed metastases. At 6 months of follow-up, the treatment plan will be evaluated by an independent committee (surgeon, medical oncologist and nuclear physician/radiologist). |
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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 | No |
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) | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |