E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
locally advanced/metastatic squamous cell carcinoma of the penis |
Neoplasie spinocellulari del pene in fase localmente avanzata/metastatica |
|
E.1.1.1 | Medical condition in easily understood language |
locally advanced/metastatic squamous cell carcinoma of the penis |
Neoplasie spinocellulari del pene in fase localmente avanzata/metastatica |
|
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 | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 |
Evaluation of the activity of Dacomitinib in squamous cell carcinoma of the penis |
Valutazione dell'attivita' di dacomitinib nelle neoplasie spinocellulari del pene |
|
E.2.2 | Secondary objectives of the trial |
Safety and toxicity |
Sicurezza e tossicita' |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Cytologically or histologically proven diagnosis of SCC of the penis.
• Histologically (Tru-cut biopsy) proven diagnosis of loco-regional nodal disease will be required in all cases except for those with unequivocal lymphadenopathy.
• Uni- or bidimensionally measurable disease.
• Clinical stage N2-3 and/or M1 (TNM 2002).
• Locoregional relapse after prior major surgery/ies (either single or multiple).
• Age 18-75.
• Written informed consent.
• ECOG performance status of at least 1.
• Neither prior chemotherapy nor treatment with any targeted agent.
• No use of any investigational agents within 4 weeks of study inclusion.
• Adequate bone marrow, liver and renal function. |
• Consenso informato scritto.
• Età ≥ 18 anni.
• ECOG performance status 0-1.
• Diagnosi citologicamente o istologicamente confermata di carcinoma spinocellulare del pene (la conferma diagnostica di malattia linfonodale è richiesta in tutti i casi).
• Malattia localmente avanzata/metastatica (stadio clinico N2-3 o M1 – TNM 2002).
• Ricaduta/progressione dopo precedente chirurgia linfonodale.
• Nessun precedente trattamento sistemico per la patologia oggetto di studio, ad esclusione del trattamento con VBM (vinblastina, bleomicina, methotrexate) per malattia superficiale se eseguito < 6 mesi dal tempo di arruolamento in studio.
• Malattia misurabile, definita come la presenza di ≥ 1 lesione misurabile uni-dimensionalmente con metodiche convenzionali (TC) di ≥ 2 cm o di ≥ 1 cm se misurata con TC spirale.
• Adeguata funzione midollare, epatica e renale in accordo ai valori riportati in full protocol.
• Aspettativa di vita di almeno 12 settimane.
• Possibilità e disponibilità a seguire le procedure previste dal protocollo. |
|
E.4 | Principal exclusion criteria |
Excluded Medical Conditions
• History of any one or more of the following cardiovascular conditions within the past 6 months:
o Cardiac angioplasty or stenting.
o Myocardial infarction.
o Unstable angina.
o Coronary artery by-pass graft surgery.
o Symptomatic peripheral vascular disease.
o Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA).
o Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted).
o Screening ECG with a QTc>450 msec, congenital long QT syndrome, history of sustained ventricular tachycardia, history of ventricular fibrillation or torsade de pointes, bradycardia defined as heart rate < 50 bpm (patients with a pacemaker and heart rate > 50 bpm are eligible).
o Uncontrolled hypertension.
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug.
• History of HIV infection or active chronic hepatitis B or C.
• Active clinically serious infections (> grade 2 NCI-CTC version 4.0).
• Patients with seizure disorder requiring medication (such as steroids or anti-epileptics).
• History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
• Patients undergoing renal dialysis.
• 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 or any cancer curatively treated > 5 years prior to study entry.
• Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results.
• Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
• Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study.
• Patients unable to swallow oral medications.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug.
Excluded therapies and medications, previous and concomitant
• Treatment with any of the following anti-cancer therapies:
o radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of PF-299804 OR
o chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of PF-299804.
• (Palliative radiotherapy will be allowed).
• Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study].
• Prior exposure to study drug. |
Co-morbidità escluse:
• Importanti patologie cardiovascolari nei 6 mesi che precedono l’inizio di PF-0299804, quali:
o Infarto miocardico (IM), angina instabile (l’IM a più di 6 mesi dall’ingresso nello studio è ammesso), scompenso cardiaco di grado ≥ 2 secondo i criteri NYHA, aritmie di qualsiasi natura che richiedano l’uso di farmaci (beta-bloccanti o digossina sono permessi), ipertensione (PA media > 140/90 mm/Hg) non controllata, prolungamento dell’intervallo QT (QTc) > 450 msec.
o Storia di infarti cerebro-vascolari, embolia polmonare o trombosi venosa profonda non trattata entro i 6 mesi che precedono l’inizio del protocollo.
• Infezione da HIV o epatite cronica attiva di tipo B e C.
• Infezioni clinicamente serie in fase attiva (di grado > 2 dei CTCAE v.4.03).
• Metastasi cerebrali o meningee sintomatiche (a meno di un tempo > 6 mesi da un precedente trattamento curative e malattia clinicamente stabile al momento dell’ingresso nello studio).
• Anamnesi positiva per crisi epilettiche che richiedono specifico trattamento medico (come cortico-steroidi e anti-epilettici).
• Seconda neoplasia pregressa o concomitante fatta eccezione per il carcinoma in situ della cervice, il carcinoma basocellulare o qualsiasi altra neoplasia trattata in modo radicale ad un tempo > 5 anni rispetto alla data di ingresso nello studio.
• Presenza di infezione non controllata.
• Nota ipersensibilità a farmaci chimicamente correlabili a PF-0299804.
• Presenza di qualsiasi condizione medica, disfunzione metabolica o psichiatrica che possa limitare la piena osservanza delle procedure dello studio o aumentare il rischio associato all’assunzione del farmaco.
Terapie oncologiche e altri farmaci esclusi, pregressi o concomitanti:
• Ogni chemioterapia o immunoterapia sia durante il trattamento che precedenti.
• Radioterapia, chirurgia o embolizzazione tumorale durante o entro 14 giorni dall’arruolamento nello studio (la radioterapia a scopo palliativo è ammessa).
• Pregresso trattamento con PF-0299804. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Response rate |
Risposta obiettiva |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Number of adverse events, overall survival, progression free survival |
Numero di eventi avversi e sopravvivenza globale, sopravvivenza libera da progressione |
|
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 | 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 | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.6 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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 40 |
E.8.9.1 | In the Member State concerned days | 0 |