E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Breast Cancer |
Carcinoma metastatico della mammella |
|
E.1.1.1 | Medical condition in easily understood language |
Metastatic Breast Cancer |
Carcinoma metastatico della mammella |
|
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 | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065430 |
E.1.2 | Term | HER-2 positive breast cancer |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To provide continued T-DM1 therapy as single agent T-DM1 or in combination with paclitaxel or with pertuzumab ± paclitaxel to HER2-positive breast cancer patients who were previously enrolled in a Genentech/Roche-sponsored T-DM1 study and who derived benefit from the therapy administered in the parent study (patients must demonstrate no evidence of systemic disease progression and an acceptable safety profile at the completion of the parent study or at the time of the parent study closure.) - To collect safety data with regard to long-term administration of single agent T-DM1 or T-DM1 administered in combination with paclitaxel or with pertuzumab ± paclitaxel. |
•Prolungare la somministrazione di T-DM1 in monoterapia o in associazione con paclitaxel o con pertuzumab ± paclitaxel, in pazienti affetti da carcinoma mammario HER2-positivo precedentemente arruolati in uno studio con T-DM1 sponsorizzato da Genentech/Roche e che hanno tratto beneficio dal trattamento somministrato nello studio originario (i pazienti non devono presentare alcuna evidenza di progressione sistemica della patologia e devono dimostrare un profilo di sicurezza accettabile al completamento o alla chiusura dello studio originario). •Raccogliere dati di sicurezza circa la somministrazione a lungo termine di T-DM1 in monoterapia o T-DM1 in associazione con paclitaxel o con pertuzumab ± paclitaxel. |
|
E.2.2 | Secondary objectives of the trial |
Not applicable |
NON APPLICABILE |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Completed single-agent T-DM1 or combination T-DM1 treatment on the parent study or who continue to receive single-agent T-DM1 or combination T-DM1 treatment at the time of the parent study closure and received the last study drug dose within the 6 weeks prior to the first scheduled dose of study therapy on the extension study; - Expectation by the investigator that the patient may continue to benefit from additional single-agent T-DM1 or combination T-DM1 treatment; - Women of childbearing potential and men with partners of childbearing potential, must be willing to use a highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner, and to continue the use of contraception for the duration of study treatment and for at least 6 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the pregnancy. |
- Pazienti che hanno concluso il trattamento con T-DM1 come singolo agente o in combinazione nell’ambito dello studio originario o pazienti che continuano a ricevere T-DM1 come singolo agente o in combinazione al momento della chiusura dello studio originario e che hanno ricevuto l’ultima dose di farmaco nelle 6 settimane antecedenti la prima dose di farmaco sperimentale programmata nell’ambito dello studio di estensione; - Pazienti che, secondo la valutazione dello sperimentatore, possono continuare a beneficiare di un trattamento con T-DM1 come singolo agente o in combinazione; - Donne potenzialmente fertili e uomini con partner potenzialmente fertili, devono essere disposti ad usare un metodo contraccettivo non ormonale altamente efficace, o due forme di contraccezione non ormonali efficaci, e ne continuino l’uso di contraccezione per tutta la durata dello studio e per almeno 6 mesi dopo l’ultima dose di farmaco assunta. Uomini le cui partner sono in stato di gravidanza dovrebbero usare il preservativo per tutta la durata della gravidanza. |
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E.4 | Principal exclusion criteria |
-Adverse events leading to single-agent T-DM1 or combination T-DM1 treatment discontinuation in the parent study; -Ongoing serious adverse events from the parent study; -Progressive disease (except for isolated brain metastases under certain conditions as described in Section 3.1) on single-agent T-DM1 or a T-DM1−containing regimen during parent study or before starting the extension study; -Peripheral neuropathy of Grade ≥ 3 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0;
-History of symptomatic congestive heart failure ([CHF]; New York Heart
Association [NYHA] Classes II−IV), ventricular arrhythmia requiring treatment,current unstable angina, or history of myocardial infarction within 6 months prior to study entry;
-Severe dyspnea at rest due to complications of advanced malignancy
or current requirement for continuous oxygen therapy;
-Current severe, uncontrolled systemic disease (e.g., clinically significant
cardiovascular, pulmonary, or metabolic disease);
-Major surgical procedure or significant traumatic injury within 28 days prior to study entry or anticipation of the need for major surgery during the course of study treatment;
-Current pregnancy or lactation;
-History of receiving any investigational treatment or other systemic therapy directed at controlling cancer (e.g.,chemotherapy, Herceptin, etc.) since the patient’s last study drug dose in the parent study;
-History of hypersensitivity with previous T-DM1 or any agent used with T-DM1 in the parent study, precluding further dosing;
-Assessed by the investigator to be unable or unwilling to comply with
the requirements of the protocol. |
-Eventi avversi correlati all’interruzione del trattamento con T-DM1 come singolo agente o in combinazione nell’ambito dello studio originario;
-Eventi avversi seri che hanno avuto inizio durante lo studio originario e che sono ancora in corso;
-Progressione di malattia (ad eccezione delle metastasi cerebrali isolate in particolari condizioni come descritto nella sezione 3.1) verificatasi durante il trattamento con T-DM1 come singolo agente o con un regime di terapia contenente T-DM1 nell’ambito dello studio originario o prima dell’inizio dello studio di estensione; -Neuropatia periferica di grado ≥ 3 secondo i criteri NCI-CTCAE versione 3.0;
-Anamnesi di insufficienza cardiaca congestizia di classe II-IV secondo i criteri della New York Heart Association - NYHA, aritmia ventricolare che richiede trattamento, angina instabile in atto o storia di infarto miocardico nei 6 mesi precedenti l’ingresso nello studio;
-Dispnea grave a riposo conseguente a complicazioni della neoplasia avanzata o in atto richiedente ossigenoterapia in maniera continuativa;
-Malattia sistemica in atto, grave, non controllata (per esempio malattia cardiovascolare, polmonare o metabolica clinicamente significativa);
-Interventi di chirurgia maggiore o traumi significativi nei 28 giorni antecedenti l’ingresso in studio o anticipata necessità di intervento chirurgico durante il trattamento in studio;
-Gravidanza o allattamento in atto;
-Anamnesi di trattamento sperimentale o altro trattamento sistemico per la cura del cancro (per esempio chemioterapia, Herceptin etc.) dopo l’ultima dose di farmaco sperimentale ricevuto nell’ambito del protocollo originario;
-Anamnesi di ipersensibilità al T-DM1 o ad altro agente usato in combinazione con T-DM1 nello studio originario che preclude la somministrazione di ulteriori dosi;
-Pazienti valutati dallo sperimentatore non in grado di seguire i requisiti del protocollo. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Incidence of adverse events leading to T-DM1 discontinuation or dose reduction. - Incidence of all adverse events and serious adverse events. |
- Incidenza degli eventi avversi che comportano l’interruzione o la riduzione della dose di T-DM1. - Incidenza di tutti gli eventi avversi e degli eventi avversi seri. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of Study |
Fine dello studio |
|
E.5.2 | Secondary end point(s) |
Not applicable |
NON APPLICABILE |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Not applicable |
NON APPLICABILE |
|
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 | 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
| 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 | 48 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Canada |
Chile |
Israel |
Mexico |
Peru |
United States |
|
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
|
Treatment can continue until the earlier of the following outcomes: disease progression (with the exception of pts with isolated brain metastases under certain conditions, as described in Section 3.1 of the protocol), unacceptable toxicity, study closure. |
Il trattamento potrà continuare fino a qunado uno dei seguenti eventi si verifichi per primo: progressione di malattia (ad eccezione delle metastasi cerebrali isolate, come descritto nel protocollo sez.3.1),tossicità inaccettabile, chiusura studio. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |
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 |