E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with HER2 positive metastatic or locally recurrent adenocarcinoma of the breast |
Pazienti con carcinoma mammario metastatico o con recidiva locale HER2 positivo |
|
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 | 10006174 |
E.1.2 | Term | Breast adenocarcinoma recurrent |
E.1.2 | System Organ Class | 100000004864 |
|
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 | 10065348 |
E.1.2 | Term | Breast adenocarcinoma metastatic |
E.1.2 | System Organ Class | 100000004864 |
|
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 determine the preliminary antitumor activity of the combination in terms of progression-free survival (PFS) |
Determinare l'attivita' antitumorale della combinazione in termini di tempo alla progressione |
|
E.2.2 | Secondary objectives of the trial |
To determine the objective response rate (RR) and overall survival (OS).
To evaluate the safety of this regimen |
Determinare la percentuale di risposte obiettive e la sopravvivenza globale.
Valutare la tossicita' di regime terapeutico |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Written informed consent (informed consent document to be approved by the Independent Ethics Committee [IEC]) obtained prior to any study-specific procedure
Age >=18 years
Able to comply with the protocol
Histologically or cytologically confirmed, HER2-positive (IHC3+ or FISH), pre- or post-menopausal women with adenocarcinoma of the breast with measurable or evaluable LR or metastatic disease, who are candidates for second-line chemotherapy. Locally recurrent disease must not be amenable to radiation therapy or resection with curative intent
Subjects must have refractory breast cancer defined as progression to first line chemotherapy which included trastuzumab in the locally advanced or metastatic setting or relapsed within 6 months of completing adjuvant therapy which included trastuzumab.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
Life expectancy of >=12 weeks
Prior adjuvant or in metastatic disease endocrine therapy is allowed
One prior chemotherapeutic regimen for the LR/metastatic disease including trastuzumab (Cumulative dose of previous anthracycline in the adjuvant setting superior of 540mg/mq for epirubicin and 360 mg/mq for doxorubicin (provided that patients have been off-treatment for at least one year).
Prior radiation therapy is allowed if:
delivered in the adjuvant setting as a part of the treatment of early breast cancer (at least 4 weeks before inclusion in the study)
delivered prior to study entry for the relief of metastatic bone pain, provided that no more than
30% of marrow-bearing bone has been irradiated (if using chemotherapy backbone which is highly myelosuppressive)
Adequate haematological function
Adequate liver function
Adequate renal function
14. Cardiac ejection fraction within the institutional range of normal (> 50%) as measured by echocardiogram or MUGA scan. Note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution.
Premenopausal patients should not be pregnant or breast-feeding. Women with an intact uterus (unless amenorrhoeic for the last 24 months) must have a negative serum pregnancy test within 28 days prior to inclusion into the study. If a serum pregnancy test is not performed within 7 days prior to the first dose of treatment, a confirmatory urine test (within 7 days prior to the first dose of treatment) is required. |
Firma del consenso informato scritto ottenuta prima dell'ingresso in studio
Eta' >=18 anni
Capacita' di attenersi alle regole dello studio
Pazienti in pre o post menopausa con carcinoma mammario misurabile e/o valutabile in recidiva locale e/o metastasi a distanza confermato citologicamente o istologicamente, Her 2 positivo.
Le pazienti devono avere una malattia in progressione ad una prima linea di trattamento che includa il trastuzumab per la malattia localmente avanzata o metastatica o in ripresa entro 6 mesi dal completamento di una terapia adiuvante che comprenda trastuzumab
Performance status Eastern Cooperative Oncology Group (ECOG) (PS) 0-2.
Aspettanza di vita >= 12 settimane
Permessa precedente terapia endocrina sia come adiuvante sia nel trattamento della malattia metastatica
Obbligatorio un trattamento di prima linea comprendente trastuzumab
Permessa una pregressa radioterapia:
somministrata in fase adiuvante come parte del trattamento locale conservativo
somministrata a scopo antalgico per metastasi ossee su non piu' del 30% del midollo osseo
Funzionalita' ematologica adeguata
Funzionalita' epatica adeguata
Funzionalita' renale adeguata
Funzionalita' cardiaca valutata con ecocardiografia o MUGA Scan nei limiti
Test di gravidanza negativo per le pazienti in pre menopausa |
|
E.4 | Principal exclusion criteria |
More than 1 line of chemotherapy for LR or mBC
Concomitant hormonal therapy for LR or metastatic disease, however previous hormonal therapy is allowed for adjuvant, LR, or mBC
Patients must have received no radiation therapy for the treatment of metastatic disease (apart from those who received it for the relief of metastatic bone pain and with the precautions mentioned above)
Evidence of CNS metastases (even if previously treated). If suspected, the patient should be scanned within 28 days prior to enrolment to rule out CNS metastases
Pre-existing peripheral neuropathy NCI CTC-AE Grade >2 at enrolment
Clinically significant (i.e. active) cardiovascular disease for example CVA (≤ 6 months before enrolment), myocardial infarction (≤ 6 months before enrolment), unstable angina, congestive heart failure (CHF) NYHA Class ≥II, serious cardiac arrhythmia requiring medication during the study, which might interfere with regularity of the study treatment, or not controlled by medication
Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) during the study and for a period of 6 months following the last administration of treatment.
Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment
Known hypersensitivity to lapatinib and any of its excipients, and any of the chemotherapies
Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications |
Piu' di una linea di chemioterapia per le recidive locali e/o per la malattia metastatica
Non e' ammessa una ormonoterapia concomitante mentre sono ammessi precedenti trattamenti ormonali per la malattia locoregionale e/o metastatica
Non e' ammessa una radioterapia concomitante se non per i criteri prima menzionati
Presenza di metastasi cerebrali. Se clinicamente sospette e' obbligatoria la valutazione TAC o RMN entro 28 giorni dall'ingresso in studio
Presenza di neuropatia NCI CTC-AE Grado >2
Malattie cardiovascolari clinicamente significative esempio CVA (≤ 6 mesi prima dell'inizio studio), infarto miocardico (≤ 6 mesi prima dell'inizio studio), angina instabile, insufficienza cardiaca congestizia (CHF) NYHA Classe ≥II, grave aritmia cardiaca non controllata dal trattamento specifico
Pazienti in premenopausa che non usano un metodo contraccettivo efficace
Partecipazione ad altro studio clinico da meno di 28 giorni o trattamento sperimentale con altro farmaco in corso
Ipersensibilita' nota a lapatinib e/o ai farmaci chemioterapici della combinazione in studio
Evidenza di ogni altra malattia o di dati clinici e/o di laboratorio che controindichino il trattamento sperimentale proposto |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To determine the preliminary antitumor activity of the combination in terms of progression-free survival (PFS) |
Determinare l'attivita' antitumorale della combinazione in termini di tempo alla progressione |
|
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
| 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 | 6 |
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 | 18 |
E.8.9.1 | In the Member State concerned days | 0 |