E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
relapsed and/or metastatic, castration resistant, salivary gland cancer |
tumore delle ghiandole salivari resistente alla castrazione, ricorrente e/o metastatico |
|
E.1.1.1 | Medical condition in easily understood language |
relapsed and/or metastatic, castration resistant, salivary gland cancer |
tumore delle ghiandole salivari resistente alla castrazione, ricorrente e/o metastatico |
|
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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10026677 |
E.1.2 | Term | Malignant salivary gland cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Response rate |
Tasso di risposta |
|
E.2.2 | Secondary objectives of the trial |
- Disease Control Rate (DCR)
- Incidence of adverse events (AEs), according to the National Cancer
- Institute Common Toxicity Criteria (NCI-CTC) version 4.0
- Progression free survival
- Overall survival
|
- tasso di controllo della malattia
- incidenza di eventi avversi, secondo i criteri del National Cancer Institute Common Toxicity (NCI-CTC) versione 4.0
- sopravvivenza libera da progressione
- sopravvivenza globale
|
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Farmacogenomic: Version 1.0 - 18 March 2014 |
Farmacogenomica: Versione 1.0 del 18 Marzo 2014 |
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E.3 | Principal inclusion criteria |
- Signed informed consent
- Histologically or cytologically confirmed salivary glands cancer.
- At least, one target lesion defined as RECIST 1.1 (clear progression of disease is required in the presence of one target lesion previously treated with radiotherapy
- Clinical and/or radiological progression of disease on ADT
- No limits are required for the number of previous chemotherapy lines
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
- Hemoglobin ≥ 9.0 g/dL independent of transfusion
- Platelet count ≥ 100,000/μL
- Serum albumin ≥ 3.0 g/dL
- Serum creatinine <1.5 x upper limit of normal (ULN) or a calculated creatinine clearance ≥ 60 mL/min
- Serum potassium ≥3.5 mmol/L
- Able to swallow the study drug whole as a tablet
- Patients with treated brain metastases, stable within the last three months, are allowed
|
Firma consenso informato
- Età maggiore di 18 anni compiuti
- Diagnosi di tumore delle ghiandole salivari istologicamente o citologicamente confermata
- Almeno una lesione misurabile secondo criteri RECIST (è richiesta progressione di malattia evidente in caso di lesione target unica precedentemente trattata con radioterapia)
- Progressione clinica o radiologica al blocco androgenico totale
- ECOG Performance Status 0-1
- Funzione midollare adeguata: neutrofili > 1.5 x 109/L, piastrine > 100 x 109/L, emoglobina > 9 g/dL
- disponibilità di tessuto tumorale in sede tumore primitivo o recidiva
- Disponibilità di prelievi ematici prima ed in corso di trattamento
- Proseguimento della deprivazione androgenica con livelli di testosterone inferiori a 50 ng per decilitro (1.7 nmol per litro)
- Non limitazione per il numero di linee chemioterapiche precedenti
- Albumina sierica ≥ 3.0 g/dL
- Creatinina sierica <1.5 x limite superiore di norma (ULN) e creatinina clearance calcolata > 60 mL/min
- Potassio sierico ≥3.5 mmol/L
- Possibilità di deglutire il farmaco come compressa intera.
- Pazienti con metastasi encefaliche trattate, sono eleggibili se la malattia encefalica è stabile nei 3 mesi precedenti l’arruolamento
- Se potenzialmente fertile, disponibiltà ad impiegare metodi contraccettivi (Pearl Index < 1; es. Contraccettivi (pillola), Spirale, impianto ormonale, patch transdermico, combinaizione di due metori di barrier (condom e diaframma) sterilizzazione, astinenza) per la durata dello studio e per le 13 settimane successive
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E.4 | Principal exclusion criteria |
- Received abiraterone acetate within the last 5 years
- Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection
- Abnormal liver functions consisting of any of the following:
Serum bilirubin ≥ 1.5 x ULN (except for subjects with documented Gilbert’s disease, for whom the upper limit of serum bilirubin is 3 mg/dL)
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2.5 x ULN
Patients with ALT and/or AST not exceeding 5X ULN due to liver mets can be enrolled
- Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥95 mmHg); subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy.
- Active or symptomatic viral hepatitis or chronic liver disease
- History of pituitary or adrenal dysfunction
- Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease or left ventricular ejection fraction (LVEF) of <50% at baseline
- History of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study drug
- Any acute toxicities due to prior chemotherapy or radiotherapy that have not resolved to a NCI-CTCAE (Version 4.0) Grade of ≤1.
- Subjects who have partners of childbearing potential who are not willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the investigator and for 13 weeks after last study drug administration
- Participation in clinical trials with other experimental agents within 30 days of study entry or concomitant treatment with other experimental drug
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry
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- Terapia con abiraterone acetato nei 5 anni precedenti
- Malattie concomitanti serie o non controllate, incluse infezioni attive e non controllate
- Funzione epatica anormale, secondo uno dei seguenti criteri:
Bilirubina sierica ≥ 1.5 x ULN (eccetto che per i soggetti con Malattia di Gilbert documentata, per cui il limite superiore è 3 mg/dL)
Aspartato aminotransferasi (AST) o alanina aminotransferasi (ALT) ≥ 2.5 x ULN
Pazienti con ALT/AST che non eccedano 5X ULN per metastasi epatiche possono essere arruolati
- Ipertensione non controllata (pressione sistolica ≥160 mmHg o pressione diastolica ≥95 mmHg); soggetti con storia di ipertensione controllata da terapia sono includibili
- Malattia epatica cronica o epatite virale attiva o sintomatica
- Storia di disfunzione surrenalica o pituitaria
- Cardiopatia o vasculopatia clinicamente significativa, quali scompenso cardiaco NYHA III-IV, coronaropatia non controllata, cardiomiopatia o aritmia non controllata, pregresso infarto miocardico nei 6 mesi precedenti, frazione di eiezione del ventricolo sinistro <50% del baseline
- Storia di disordine gastrointestinale (disordine medico o chirurgia estensiva) che può interferire con l’assorbimento del farmaco in studio
- Altre condizioni mediche concomitanti che possano inficiare la possibilità del paziente di partecipare allo studio
- Qualsiasi tossicità acuta dovuta a chemioterapia o radioterapia precedente (NCI-CTC V 4.0) che non sia risolta o ≤1 di grado 1
- Aver partecipato ad altri studi clinici o aver ricevuto qualsiasi farmaco all’interno di studio nei 30 giorni precedenti l’arruolamento
-Pregresso o tumore sincrono in altro sito o altra istologia, eccetto carcinoma cervical in situ, basalioma trattato; tumore vescicale superficiale [Ta, Tis & T1] o qualsiasi altro tumore trattato in maniera curativa > 3 anni prima dell’ingresso in studio.
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|
E.5 End points |
E.5.1 | Primary end point(s) |
To assess the activity of abiraterone acetate plus prednisone in castration resistant SGCs |
Valutare l'attività di abiraterone acetato più prednisone nei tumori delle ghiandole salivari resistenti castrazione |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Disease Control Rate (DCR)
• Incidence of adverse events (AEs), according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0
• Progression free survival
• Overall survival
|
- tasso di controllo della malattia
- incidenza di eventi avversi, secondo i criteri del National Cancer Institute Common Toxicity (NCI-CTC) versione 4.0
- sopravvivenza libera da progressione
- sopravvivenza globale
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | 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 | Yes |
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
|
LVLS |
ultima visita ultimo soggetto |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |