E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
BRAFV600-mutation positive patients with unresectable locally
advanced or metastatic melanoma |
PAZIENTI AFFETTI DA MELANOMA LOCALMENTE AVANZATO O METASTATICO, NON RESECABILE, POSITIVI ALLA MUTAZIONE BRAFV600 |
|
E.1.1.1 | Medical condition in easily understood language |
skin cancer |
tumore della pelle |
|
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 | PT |
E.1.2 | Classification code | 10025650 |
E.1.2 | Term | Malignant melanoma |
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 | PT |
E.1.2 | Classification code | 10027480 |
E.1.2 | Term | Metastatic malignant melanoma |
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 evaluate the efficacy of vemurafenib in combination with GDC-0973,compared with vemurafenib and placebo, in previously untreated
BRAFV600 mutation-positive patients with unresectable locally advanced
or metastatic melanoma, as measured by prolongation of progression-free survival (PFS), as assessed by the study site investigator. |
Valutare l’efficacia di vemurafenib in combinazione con GDC-0973, rispetto a vemurafenib e placebo, in pazienti affetti da melanoma localmente avanzato o metastatico, non resecabile, positivi alla mutazione BRAFV600 e precedentemente non trattati, tramite misurazione del prolungamento della sopravvivenza senza progressione (Progression-Free Survival, PFS), come valutata dallo sperimentatore del centro dello studio. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of vemurafenib in combination with GDC-0973, compared with vemurafenib and placebo, in previously untreated
BRAFV600 mutation-positive patients with unresectable locally advanced
or metastatic melanoma, as measured by overall survival (OS), objective response rate (ORR), and duration of response (DOR). |
Valutare l’efficacia di vemurafenib in combinazione con GDC-0973, rispetto a vemurafenib e placebo, in pazienti affetti da melanoma localmente avanzato o metastatico, non resecabile, positivi alla mutazione BRAFV600 e precedentemente non trattati, tramite misurazione della sopravvivenza complessiva (Overall Survival, OS), del tasso di risposta obiettiva (Objective Response Rate, ORR) e della durata della risposta (Duration Of Response, DOR). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-≥ 18 years of age
•Stage IIIc or Stage IV melanoma harboring BRAF V600 mutation
-BRAF V600 mutation must be confirmed by cobas 4800 BRAF V600 mutation test
-Measurable disease according to RECIST 1.1
-Women of childbearing potential with negative serum pregnancy test prior to randomization
-Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
-Adequate baseline organ function |
- età ≥18 anni
- Pazienti con melanoma di stadio IIIc non resecabile o di stadio IV metastatico, con positività alla mutazione BRAFV600
- positività alla mutazione BRAFV600
confermata usando il test cobas 4800
-Malattia misurabile in base ai criteri RECIST v1.1.
-Test di gravidanza sul siero negativo nei 10 giorni che precedono l’inizio della somministrazione nelle donne potenzialmente fertili.
-Stato prestazionale dell’Eastern Cooperative Oncology Group di 0 o 1
-Adeguata funzione ematologica e d’organo terminale |
|
E.4 | Principal exclusion criteria |
•Any prior use of a BRAF or MEK inhibitor
•Prior systemic anti-cancer treatment in the advanced or metastatic
setting; prior systemic treatment in the adjuvant setting is allowed
•History of another malignancy except subjects who have been disease
free for 3 years or have completely resected non-melanoma skin cancer.
•Patients with active CNS lesions (including carcinomatous meningitis)
are excluded. However, patients are eligible if:
a)all known CNS lesions have been treated with stereotactic therapy or
surgery, AND
b)no evidence of clinical and radiographic disease progression in the CNS for ≥ 3 weeks after radiotherapy or surgery.
Whole brain radiotherapy is not allowed with the exception of patients
who have had definitive resection or stereotactic therapy of all
radiologically detectable parenchymal brain lesions.
•Evidence of cardiovascular risk (LVEF < LLN; QTc ≥ 450 msec; blood
pressure ≥140/90 mmHg which cannot be controlled by antihypertensive
therapy)
•History, risk factors for or evidence of neurosensory retinal detachment, retinal vein occlusion or neovascular macular degeneration. |
-Anamnesi di precedente trattamento inibitorio della via metabolica di RAF o MEK.
-precendente trattamento antitumorale sistemico per tumori avanzati o metastatici;le terapie adiuvanti sono consentite;
-Neoplasia attiva diversa dal melanoma. I pazienti con una precedente neoplasia riscontrata negli ultimi 3 anni sono da escludere, tranne quelli con carcinoma cutaneo basocellulare (Basal Cell Carcinoma, BCC) o carcinoma cutaneo squamocellulare (Squamous Cell Carcinoma, SCC) resecati, melanoma in situ, carcinoma in situ della cervice e carcinoma in situ mammario.
-pazienti con lesioni al SNC attive (compresa la meningite carcinomatosa). Tuttavia, i pazienti sono idonei se:
a) Tutte le lesioni al SNC note sono state trattate con terapia stereotassica o intervento chirurgico, E
b) Non vi è stata alcuna evidenza di progressione clinica e radiografica della malattia nel SNC per ≥ 3 settimane dopo la radioterapia o l’intervento chirurgico. La radioterapia encefalica integrale non è consentita, con l’eccezione di pazienti che hanno avuto una resezione definitiva o una terapia stereotassica di tutte le lesioni del parenchima encefalico radiologicamente rilevabili.
-Evidenza di rischio cardiovascolare (LVEF < LLN; QTc ≥ 450 msec; pressione arteriosa ≥140/90 mmHg non controllata con antipertensivi)
-Anamnesi o evidenza di patologia retinica dall’esame oftalmologico, ritenuta essere fattore di rischio per il distacco della retina neurosensoriale, occlusione venosa retinica (Retinal Vein Occlusion, RVO) o degenerazione maculare neurovascolare |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival |
sopravvivenza libera da progressione |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
approx. 16 months |
circa 16 mesi |
|
E.5.2 | Secondary end point(s) |
1. Overall Survival
2. Overall Response Rate
3. Duration of Response |
1. sopravvivenza complessiva
2. tasso di risposta obiettiva
3. durata della risposta |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. approx. 36 months
2. Time Frame: approx. 16 months
3. Duration of Response |
1. circa 36 mesi
2.intervallo di tempo approssimativo di 16 mesi
3.durata della risposta |
|
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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability,exploratory exposure-response analysis,health-related QOL,biomarker profiling |
tollerabilità, analisi esposizione-risposta, qualità della vita, analisi dei biomarcatori |
|
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 102 |
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 |
Australia |
Brazil |
Canada |
Israel |
New Zealand |
Switzerland |
Turkey |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The study will end when all patients enrolled have been followed until
death, withdrawal of consent, lost to follow-up, or the Sponsor decides
to end the trial, whichever occurs first. |
Lo studio terminerà quando tutti i pazienti arruolati saranno stati seguiti fino al decesso o al ritiro del consenso o persi al follow-up o finché lo Sponsor non deciderà di chiudere la sperimentazione, a seconda di quale evento si verifichi prima |
|
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 | 46 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 46 |
E.8.9.2 | In all countries concerned by the trial days | 0 |