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 establish whether single-agent cDDP yields a response rate considered worthwhile to be further explored in metastatic breast cancer patients with more than 5 CTCs/7.5 mL of blood harboring a favorable CTC cDDP-sensitivity profile. |
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E.2.2 | Secondary objectives of the trial |
• To assess significant cDDP toxicity in metastatic breast cancer patients in this setting • To explore differences in time to treatment switch (TTS) and/or overall survival (OS) between metastatic breast cancer patients with more than 5 CTCs/7.5 mL of blood harboring a favorable CTC cDDP-sensitivity profile and metastatic breast cancer patients with less than 5 CTCs/7.5mL or more than 5 CTCs/7.5mL and an unfavorable CTC cDPP-sensitivity profile • To determine differences in the 96 gene CTC panel expression profiles between cDDP responders and non-responders (regardless of the patients’ cDDP-sensitivity profile) • To explore the predictive value of a functional assay for homologous recombination deficiency assessed in tissue from metastatic lesions, for the response to cDDP therapy • To investigate the concordance between the CTC cDPP-sensitivity profile and the cDDP-sensitivity profile assessed in metastatic tissue
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Female patient with metastatic breast cancer who has been pretreated with at least anthracycline and taxane-based chemotherapy in the adjuvant and/or metastatic setting • Measurable disease according to RECIST 1.1, ie at least one measurable lesion on CT-scan where the longest diameter in the plane of measurement is a minimum size of 10mm • Age ≥ 18 years • WHO performance status ≤2 • Adequate hematological functions defined as ANC ≥ 1.0 x 109/L, platelets ≥ 100 x 109/L • Adequate renal function defined as creatinin clearance ≥ 60 mL/min (Cockcroft Gault) • Patients with reproductive potential must use a reliable method of contraception • Written informed consent
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E.4 | Principal exclusion criteria |
• Other anticancer chemotherapy, use of biological response modifiers, or immunotherapy within two weeks prior to treatment start. Hormonal antitumor treatment within one week prior to treatment start. • Hearing loss of at least Common Terminology Criteria for Adverse Events (CTCAE) grade 2 • Neuropathy of at least CTCAE grade 2 • Pregnant or lactating patients • Serious illness or medical unstable condition prohibiting adequate treatment and follow-up • Symptomatic CNS metastases (the presence of at least one key symptom in combination with radiologic evidence (positive contrast-enhanced CT or MRI of the brain)) • History of psychiatric disorder that would prohibit the understanding and giving of informed consent or that would prohibit adequate follow-up
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study will be the response rate (RR) (complete response (CR) and partial response (PR)) according to RECIST version 1.1 following 4 cycles of cDDP in the three groups of patients (5 or more CTCs/7.5 mL of blood and a favorable cDDP-sensitivity profile, ≥5 CTCs/7.5 ml and an unfavorable CTC cDDP-sensitivity profile and <5 CTCs/7.5 mL of blood). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Enumeration and characterization of CTC's at baseline. Response rate following 4 cycles of cDDP. |
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E.5.2 | Secondary end point(s) |
Secondary objectives include exploratory analyses assessing the time to treatment switch (TTS), overall survival (OS) and cDDP toxicity in the three groups. Other secondary endpoints include a retrospective comparison of the 96 gene CTC panel expression profiles between cDDP responders and non-responders following the fourth cDDP cycle (regardless of the patients’ cDDP sensitivity profile) and the exploration of a possible association between a functional assay for predicting homologous recombination deficiency in metastatic tissue and clinical outcome as well as the accordance between the CTC cDDP-sensitivity profile and a metastatic tissue cDDP-profile. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
TTS, OS and cDDP toxicity: evalation at end of study (date of last visit last subject) Metastatic tissue evaluation: at baseline |
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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 | Yes |
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
| 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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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LVLS, until PD or 6 months following the initial administration of cDDP (in this last subject) |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |