E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Triple Negative Breast Cancer recurrence |
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E.1.1.1 | Medical condition in easily understood language |
Patients with Triple Negative Breast Cancer recurrence |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10075566 |
E.1.2 | Term | Triple negative 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 |
To assess the concordance for tumor lesion detection using 89Zr-TLX250 PET/CT versus a conventional 18FDG PET/CT scan where comparison will be made on a per lesion analysis basis |
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E.2.2 | Secondary objectives of the trial |
1. To determine the percent of total tumor burden (whole body) detected on 89Zr-TLX250 PET/CT scan compared to that defined on 18FDG PET/CT used as the reference.
2. To assess the correlation between the normalized uptake values (SUV) of 89Zr-TLX250 and CAIX histological expression if a biopsy is done.
3. To confirm the perfect safety and tolerability of 89Zr-TLX250 and assess the generation of human anti-chimeric antibodies in response to the girentuximab.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
2. Female or male, Age ≥ 18 years at time of study entry.
3. Primitive triple negative breast cancer proven histologically, defined according to the following criteria:
- Estrogen receptors <10%.
- And progesterone receptors <10%.
- And HER2 not amplified or not overexpressed.
4. BC recurrence documented by conventional imaging and/or FDG PET/CT with at least one metastasis measurable according to RECIST and/or PERCIST.
5. Consent to use a contraception method for at least 30 days after administration of 89Zr-TLX250.
6. ECOG Performance Status 0 or 1.
7. Life expectancy at least 6 months.
8. Patient has valid health insurance.
9. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
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E.4 | Principal exclusion criteria |
1. History of another primary malignancy except for basal cell carcinoma within the last 5 years.
2. Chemotherapy, radiotherapy, or immunotherapy within 4 weeks prior to the planned administration of 89Zr-TLX250 or continuing adverse effects (> grade 1) from such therapy (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0).
3. Planned antineoplastic therapies (for the period between IV administration of 89Zr-TLX250 and imaging).
4. Exposure to murine or chimeric antibodies within the last 5 years.
5. Previous administration of any radionuclide within 10 half-lives of the same.
6. Impossibility to hold lying motionless at least 1 hour, or known claustrophobia.
7. Serious non-malignant disease (e.g. psychiatric, infectious, autoimmune or metabolic), that may interfere with the objectives of the study or with the safety or compliance of the subject, as judged by the investigator.
8. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
9. Pregnant or likely to be pregnant or nursing patient.
10. Known hypersensitivity to girentuximab or desferoxamine.
11. Renal insufficiency with GFR ≤ 45 mL/min/ 1.73 m².
12. Persons deprived of their liberty, under a measure of safeguard of justice, under guardianship or placed under the authority of a guardian.
13. Disorder precluding understanding of trial information or informed consent.
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E.5 End points |
E.5.1 | Primary end point(s) |
Concordance study of metastatic uptake seen in 18FDG PET/CT scan and 89Zr-TLX250 PET/CT scan per "lesion" by comparing for each lesion the CT scan, 18FDG PET/CT scan and 89Zr-TLX250 PET/CT scan by assessing a ratio "Number of positive 89Zr-TLX250 lesions / Number of positive FDG lesions” and "Number of positive 89Zr-TLX250 lesions / Number of CT scan lesions”. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Percent of positive CA IX metastatic tumor burden compared to total metastatic tumor burden by 18FDG (ratio "Number of positive 89Zr-TLX250 lesions / Number of positive FDG lesions")
2. If a metastasis biopsy is conducted, assessment of the correlation between the normalized uptake values (SUV) of 89Zr-TLX250 positive lesions and CAIX histological expression will be done by comparing the 89Zr-TLX250 semi-quantitative data with the immunohistochemical results (IHC) of biopsied metastases.
3. The safety and tolerability of 89Zr-TLX250 will be evaluated by measuring and monitoring vital signs within 2 hours after injection of the radiopharmaceutical. The patient will be informed that in the event of abnormal physical signs, occurring within 24 hours after 89Zr-TLX250 administration, he must report them to the investigator for registration. The reporting period of AEs (related to 89Zr-TLX250) and SAEs cover a period of 30 days after 89Zr-TLX250 administration.
- The NCI Common Toxicity Criteria, version 5.0 reference will be used.
- HACA (Human anti-chimeric antibody) will be assessed.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |