| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Early HER2-positive breast cancer |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10006279 |
| E.1.2 | Term | Breast neoplasm |
|
| 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 |
| The primary objective is to determine whether the regimens of chemotherapy + trastuzumab + bevacizumab improve invasive disease-free survival (IDFS) relative to the regimens of khemotherapy + trastuzumab. |
|
| E.2.2 | Secondary objectives of the trial |
To determine whether: - the TCH→H regimen + bevacizumab improves IDFS relative to the TCH→H regimen alone. - the TH→FEC→H regimen + bevacizumab improves IDFS relative to the TH→FEC→H regimen alone. - the regimens of chemotherapy + trastuzumab + bevacizumab improve disease-free survival (DFS) relative to the regimens of chemotherapy + trastuzumab. - the regimen of TCH→H + bevacizumab improves DFS relative to the regimen of TCH→H alone. - the regimen of TH→FEC→H + bevacizumab improves DFS relative to the regimen of TH→FEC→H alone. - the regimens of chemotherapy + trastuzumab + bevacizumab improve overall survival (OS) relative to the regimens of chemotherapy + trastuzumab. - the TCH→H regimen + bevacizumab improves OS relative to the TCH→H regimen alone. - the TH→FEC→H regimen + bevacizumab improves OS relative to the TH→FEC→H regimen alone. Etc.
|
|
| 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 |
FARMACOGENETICA: Versione:1 Data:2008/02/01 Titolo:- Biochemical markers Obiettivi:
ALTRI SOTTOSTUDI: - Cardiovascular substudy
|
|
| E.3 | Principal inclusion criteria |
Patient-Specific and General Inclusion Criteria
1. The patient must have consented to participate and must have signed and dated both IRB-approved consent forms that conform to the guidelines of the local regulatory authority and the institution. The pre-entry central HER2 testing consent form must be signed before tumor material is sent to the central laboratory for HER2 testing.
2. Patients must be female.
3. The patient must be > 18 years old. (The minimum age for eligibility can be older than 18 years if required by local regulatory authority.)
4. The patient must have an ECOG performance status of 0 or 1.
Disease-Specific Inclusion Criteria
5. The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
6. The breast cancer must be HER2-positive based on test results as follows:
− Local testing (if available) should demonstrate that the tumor is IHC 2+ or 3+ or is considered to be HER2-positive for gene amplification by FISH, CISH, or other in situ hybridization method.
(If local IHS test results are considered equivocal, the tumor can be submitted for central HER2 testing.)
− Central testing (a requirement for ALL patients) must demonstrate that the tumor is HER2-positive which is defined as IHC 3+ and/or FISH-positive.
7. Patients must have ER analysis performed on the primary tumor prior to randomization. If ER analysis is negative, then PgR analysis must also be performed.
8. Patients must have undergone either a total mastectomy or breast conserving surgery (lumpectomy).
9. The interval between the last surgery for breast cancer (treatment or staging) and randomization must
be no more than 84 days and not less than 28 days.
10. For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins. If tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible. (Patients with margins positive for LCIS are eligible
without additional resection.)
11. For patients who undergo mastectomy, margins must be free of gross residual tumor. Patients with
microscopic positive margins are eligible.
Etc. |
|
| E.4 | Principal exclusion criteria |
Relativi alla malattia
1.Carcinoma mammario infiammatorio.
2.Carcinoma mammario controlaterale sincrono (invasivo o non-invasivo).
Stadiazione clinica
3.Evidenza clinica o radiologica definitiva di malattia metastatica. (L’imaging diagnostico del torace [obbligatorio per tutte le pazienti] e altri tipi di immagini diagnostiche [se necessario] devono essere stati ottenuti nei 3 mesi precedenti la randomizzazione.)
Anamnesi oncologica
4.Storia di carcinoma mammario invasivo ipsilaterale indipendentemente dal trattamento o di DCIS ipsilaterale trattato con escissione e RT.
5.Storia di tumore maligno non alla mammella nei 5 anni precedenti l’ingresso nello studio, fatta eccezione per i seguenti: carcinoma in situ della cervice, carcinoma in situ del colon, melanoma in situ,e carcinoma cutaneo basocellulare e squamocellulare.
6.Precedente terapia con antracicline, taxani, carboplatino, trastuzumab, o bevacizumab per qualsiasi tipo di tumore maligno.
7.Somministrazione prima della randomizzazione di trattamento per il tumore al seno attualmente diagnosticato, compresi RT, chemioterapia, e/o terapia mirata.
Terapia endocrina
8.Terapia continuativa con qualsiasi agente ormonale quali raloxifene o tamoxifene (o altri SERM) o con inibitori della aromatasi. (Le pazienti sono idonee se tali farmaci vengono interrotti prima della randomizzazione.)
Anamnesi
9.Cardiopatia (storia e/o malattia attiva) che impedirebbe l’uso dei farmaci inseriti nei regimi terapeutici studiati. Sono compresi, senza limitazione a quanto in elenco:
Cardiopatia attiva
Storia di cardiopatia
10.Ipertensione non controllata
11.Storia di crisi ipertensive o di encefalopatia ipertensiva.
12.Storia di TIA o di CVA.
13.Storia di eventi trombotici arteriosi di qualsiasi tipo nei 12 mesi precedenti la randomizzazione.
14.Vasculopatia periferica sintomatica.
15.Pneumopatia intrinseca con conseguente dispnea.
16.Diabete mellito non stabilizzato.
17.Infezione attiva o cronica richiedente terapia antibiotica soppressiva.
18.Qualsiasi emorragia significativa nei 6 mesi precedenti la randomizzazione, con l’esclusione di episodi di menorragia nelle donne in premenopausa.
19.Diatesi emorragica o coagulopatie note.
20.Necessita` di somministrazione terapeutica di coumadina o equivalenti.
21.Ulcera gastroduodenale con attivita` documentata da endoscopia nei 6 mesi precedenti la randomizzazione.
22.Storia di perforazione GI, fistole addominali, o ascesso intraaddominale.
23.Lesioni non-healing, ulcere cutanee, o fratture ossee non completamente guarite.
24.Procedura chirurgica importante, biopsia aperta, o lesione traumatica significativa nel 28 giorni precedenti il previsto inizio della terapia di studio. (Nota: il posizionamento di un accesso vascolare non e` considerato una procedura chirurgica importante).
25.Previsione della necessita` di praticare una procedura chirurgica importante durante la terapia di studio e per almeno 3 mesi dopo il completamento della terapia con bevacizumab.
26.Condizioni che proibirebbero la somministrazione di corticosteroidi.
27.Neuropatia sensoria/motoria di grado > 2, in base alla definizione data dal CTCAE del NCI v3.0.
28.Altre malattie sistemiche non maligne che impedirebbero alla paziente di ricevere il trattamento di studio o di essere seguita nel previsto follow-up.
29.Disturbi psichiatrici o dipendenze o altre condizioni che, a giudizio dello sperimentatore, impedirebbero alla paziente di rispettare i requisiti dello studio.
Ecc. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
IDFS, defined as time to local recurrence following mastectomy, invasive local recurrence in the
ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, invasive contralateral breast cancer, second primary cancer (other than squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix, colon carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer. |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| 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 | Yes |
| 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) | Yes |
| 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
| 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 | 17 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 774 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
|
| All randomised patients will be followed until death or at least until 10 years after study entry. The trial will end 10 years after the last patient was randomised. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 13 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 13 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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