E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Operated breast cancer |
Carcinoma della mammella operato
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E.1.1.1 | Medical condition in easily understood language |
Operated breast cancer |
Carcinoma della mammella operato |
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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 | LLT |
E.1.2 | Classification code | 10006190 |
E.1.2 | Term | Breast cancer invasive NOS |
E.1.2 | System Organ Class | 100000004864 |
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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 evaluate PLD (Caelyx¿) as an adjuvant chemotherapy regimen in patients with early-stage luminal B breast cancer
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valutare la fattibilit¿ del trattamento con doxorubicina liposomiale pegilata (Caelyx¿) in donne con tumore mammario Luminal B operato |
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E.2.2 | Secondary objectives of the trial |
¿ Adverse events, Tolerability (treatment completion), Breast cancer free interval (BCFI; events are reappearance of invasive breast cancer at any site including contralateral disease), Disease Free Survival (DFS) (includes second malignancies and deaths), Sites of failure, Second (non-breast) malignancy, Overall survival (OS), Causes of death |
¿ Eventi avversi, Tollerabilit¿, Intervallo libero da carcinoma mammario (breast cancer free interval, BCFI), Sopravvivenza libera da malattia (disease free survival, DFS), Sedi di recidiva, Secondi tumori, Sopravvivenza globale (overall survival, OS), Cause di morte |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Operable histologically confirmed breast cancer • Luminal B HER2-negative (ER positive, HER2 negative, and at least one of the following: Ki-67 ‘high’ (=20%) or PgR ‘negative or low’) or Luminal B HER2-positive (ER positive, HER2 over-expressed or amplified, any Ki-67, any PgR) • Early-stage (pT1-3; any nodal status) • Candidate to adjuvant chemotherapy and endocrine therapy • The tumor must be confined to the breast and axillary nodes without detected metastases elsewhere • Patients with synchronous (diagnosed histologically within 2 months) bilateral invasive breast cancer are eligible if all other criteria are met • Patients must have had surgery for primary breast cancer with no known clinical residual loco-regional disease • Margins must be negative for invasive breast cancer and DCIS • Patients should be start treatment as close to definitive surgery as possible (no later than 8 weeks) • No prior neoadjuvant or adjuvant therapy for breast cancer. Note: Radiotherapy is allowed prior to trial entry. • Raloxifene, tamoxifen, or other SERM must be discontinued at least 4 weeks before trial entry. • No hormone replacement therapy (HRT). • No hormonal therapy, except steroids for adrenal failure, hormones for non-breast cancer related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic. • No treatment with bisphosphonates, except for the treatment of osteoporosis.
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• Carcinoma mammario operato confermato istologicamente • Luminal B HER2-negativo (ER positivo, HER2 negativo, e almeno uno dei seguenti: Ki-67 ‘elevato’ (=20%) o PgR ‘negativo o basso’) o Luminal B HER2-positivo (ER positivo, HER2 iper-espresso o amplificato, qualunque Ki-67, qualunque PgR) • Stadio iniziale (pT1-3; qualunque stato linfonodale) • Candidate a chemioterapia e ad endocrinoterapia adiuvanti • Il tumore deve essere confinato alla mammella e ai linfonodi ascellari senza altre sedi di metastasi • Pazienti con carcinoma mammario sincrono (diagnosticato istologicamente entro 2 mesi) bilaterale sono eleggibili se tutti gli altri criteri sono soddisfatti • Le pazienti devono essere state sottoposte a chirurgia per carcinoma mammario senza malattia locoregionale residua • I margini devono essere negativi per carcinoma infiltrante e DCIS • Le pazienti devono iniziare il trattamento il prima possibile dopo la chirurgia (entro 8 settimane) • Nessuna precedente terapia neoadiuvante o adiuvante per il carcinoma mammario. Nota: la radioterapia è permessa prima della inclusione nello studio. • Raloxifene, tamoxifene, o altri SERM devono essere sospesi almeno 4 settimane prima della inclusione nello studio. • Nessuna terapia ormonale sostitutiva (hormone replacement therapy, HRT). • Nessuna terapia ormonale, ad eccezione di steroidi per l’insufficienza surrenalica, ormoni per patologie non correlate al carcinoma mammario (es. insulina per il diabete), o uso intermittente di desametasone come antiemetico. • Nessun trattamento con bifosfonati, eccetto per il trattamento dell’osteoporosi.
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E.4 | Principal exclusion criteria |
• Patients with a history of any prior ipsilateral or contralateral invasive breast cancer. • Patients with previous or concomitant malignancy diagnosed within the past five years. • Patients with other non-malignant uncontrolled systemic diseases that would preclude trial entry in the opinion of the investigator. Specifically not eligible are patients with uncontrolled active infection, chronic infection such as active HBV or HCV • Patients with myocardial infarction or pulmonary embolism within 6 months prior to trial entry.
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• Pazienti con storia di carcinoma mammario pregresso omolaterale o controlaterale • Pazienti con tumori pregressi o concomitanti, diagnosticati nei 5 anni precedenti • Pazienti con altre malattie sistemiche non oncologiche non controllate che potrebbero precludere l’ingresso nello studio secondo l’investigatore. In particolare, non sono eleggibili pazienti con infezioni acute non controllate, infezioni croniche (es. da HBV o HCV). • Pazienti con infarto miocardico o embolia polmonare nei 6 mesi precedenti la randomizzazione.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be to evaluate the feasibility of adjuvant PLD (Caelyx®) for each individual subject. The regimen will be considered feasible if that subject is able to achieve relative dose intensity (RDI) of at least 85% of the 8 cycles of treatment. Relative dose intensity for each subject will be calculated as follows: (1) based on each subject's body surface area (BSA), a total planned dose for PLD (Caelyx®) calculated for a full 8-cycle regimen (planned dose, PD); (2) actual total dose of PLD (Caelyx®) for the full 8-cycle regimen as collected on the case report form (actual dose, AD); (3) overall RDI = AD/PD.
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L’obiettivo primario sarà di valutare la fattibilità di un trattamento con Caelyx® adiuvante per ogni paziente. Il regime verrà considerato fattibile se quella paziente sarà in grado di raggiungere una intensità di dose relativa (relative dose intensity, RDI) di almeno 85% negli 8 cicli di trattamento. L’intensità di dose relative per ogni paziente verrà calcolata come segue: (1) dose pianificata totale di Caelyx®, basata sulla superficie corporea di ogni paziente, calcolata per un regime completo di 8 cicli (dose pianificata, DP); (2) dose effettiva totale di Caelyx® per un regime completo di 8 cicli, come riportato nelle case report form (dose effettiva, DE); (3) RDI globale = DE/DP.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
4 months from randomization of the last patient. |
4 mesi dalla randomizzazione dell’ultima paziente. |
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E.5.2 | Secondary end point(s) |
¿ Adverse events ¿ Tolerability ; ¿ Breast cancer free interval (BCFI; events are reappearance of invasive breast cancer at any site including contralateral disease) ¿ Disease Free Survival (DFS) (includes second malignancies and deaths) ¿ Sites of failure ¿ Second (non-breast) malignancy ¿ Overall survival (OS) ¿ Causes of death
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¿ Eventi avversi ¿ Tollerabilit¿ ; ¿ Intervallo libero da carcinoma mammario (breast cancer free interval, BCFI) ¿ Sopravvivenza libera da malattia (disease free survival, DFS) ¿ Sedi di recidiva ¿ Secondi tumori ¿ Sopravvivenza globale (overall survival, OS) ¿ Cause di morte
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
4 months from randomization of the last patient; 5 years |
4 mesi dalla randomizzazione dell¿ultima paziente; 5 anni |
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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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | Information not present in EudraCT |
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 | 7 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |