- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT00949702
A Study of Vemurafenib in Previously Treated Patients With Metastatic Melanoma
26 giugno 2017 aggiornato da: Hoffmann-La Roche
An Open-label Multicenter Study on the Efficacy of Continuous Oral Dosing of Vemurafenib on Tumour Response in Previously Treated Patients With Metastatic Melanoma
This open-label single arm study will assess the efficacy, safety and tolerability of Vemurafenib in previously treated patients with metastatic melanoma.
Patients will receive oral Vemurafenib [RG7204; PLEXXIKON: PLX4032] at a dose of 960 mg b.i.d.
continuously until disease progression or withdrawal from study and will be assessed at regular intervals for tumour response and tolerability.
Target sample size is <100 patients.
Panoramica dello studio
Tipo di studio
Interventistico
Iscrizione (Effettivo)
132
Fase
- Fase 2
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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New South Wales
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Newcastle, New South Wales, Australia, 2298
- Calvary Mater Newcastle; Melanoma Clinic
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Westmead, New South Wales, Australia, 2145
- Westmead Hospital; Medical Oncology and Pallative Care
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Victoria
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Melbourne, Victoria, Australia, 3000
- Peter Maccallum Cancer Institute; Medical Oncology
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California
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Los Angeles, California, Stati Uniti, 90095-6984
- UCLA - School of Medicine; Division of Hematology/Oncology
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Colorado
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Denver, Colorado, Stati Uniti, 80262
- University of Colorado
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Florida
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Tampa, Florida, Stati Uniti, 33612
- Moffitt Cancer Center
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Massachusetts
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Boston, Massachusetts, Stati Uniti, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Stati Uniti, 02115
- Dana Farber Cancer Inst. ; Dept. of Medical Oncology
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Boston, Massachusetts, Stati Uniti, 02114
- Massachusetts General Hospital;Hematology/ Oncology
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New York
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New York, New York, Stati Uniti, 10036
- New York University Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Stati Uniti, 19104-4283
- Hospital of the Uni of Pennsylvania; Section of Hematology/Oncology
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Pittsburgh, Pennsylvania, Stati Uniti, 15213
- University of Pittsburgh
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Tennessee
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Nashville, Tennessee, Stati Uniti, 37232
- Vanderbilt-Ingram Cancer Ctr
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Texas
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Dallas, Texas, Stati Uniti, 75246
- Texas Oncology-Baylor Sammons Cancer Center
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Houston, Texas, Stati Uniti, 77030
- University of Texas M.D. Anderson Cancer Center
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Inclusion Criteria:
- adult patients >/=18 years of age
- histologically confirmed metastatic melanoma (Stage IV, AJCC)
- patients must have completed and failed at least one prior standard of care regimen (e.g. DTIC, temozolomide, etc.)
- BRAF V600E positive mutation (by Roche CoDx BRAF mutation assay)
- measurable disease by RECIST criteria
- negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion
Exclusion Criteria:
- active CNS metastases on CT/MRI within 28 days prior to enrollment
- history of or known carcinomatous meningitis
- previous treatment with BRAF (sorafenib allowed) or MEK inhibitor
- cardiac dysrhythmias >2 NCI CTCAE or treatment with drugs with dysrhythmic potential
- uncontrolled hypertension(>150/100mmHg) despite optimal medical therapy
- infectious disease including HIV, HBV and HCV
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: Braccio singolo
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960 mg b.i.d.
continuous oral dosing
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Best Overall Response (BOR) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Lasso di tempo: From first treatment through September 27, 2010
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BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
Patients who never received study treatment and treated patients without any post-baseline tumor assessments were considered as non-responders.
CR: Disappearance of all target lesions, all non-target lesions, and no new lesion.
Any pathological lymph nodes must have had reduction in the short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion.
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From first treatment through September 27, 2010
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Lasso di tempo: From first treatment through September 27, 2010
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BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
Patients who never received study treatment and treated patients without any post-baseline tumor assessments were considered as non-responders.
CR: Disappearance of all target lesions, all non-target lesions, and no new lesion.
Any pathological lymph nodes must have had reduction in the short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion.
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From first treatment through September 27, 2010
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Duration of Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Lasso di tempo: From first treatment through September 27, 2010
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Duration of response was defined as the time interval between the date of the earliest qualifying response and the date of disease progression (PD) or death, only for those patients whose best overall response was complete response or partial response.
PD: At least 20% increase in the sum of diameters of target lesions compared to Nadir (smallest sum of diameters on-study), unequivocal progression of existing non-target lesions, or presence of new lesion.
For patients who were alive without progression, duration of response was censored on the date of the last evaluable tumor assessment.
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From first treatment through September 27, 2010
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Time to Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Lasso di tempo: From first treatment through September 27, 2010
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Time to response was defined as the interval between the date of the first treatment and the date of the first documentation of confirmed complete response (CR) or partial response (PR), whichever occurred first.
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From first treatment through September 27, 2010
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Progression Free Survival (PFS) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Lasso di tempo: From first treatment through September 27, 2010
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PFS was defined the time interval between the date of the first treatment and the date of progression or death from any cause, whichever occurred first.
Deaths that occurred in patients without disease progression were considered to be a PFS event on the date of death.
Patients who neither progressed nor died were censored on the date of the last evaluable tumor assessment prior to the data cutoff date.
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From first treatment through September 27, 2010
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Overall Survival
Lasso di tempo: From first treatment through September 27, 2010
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Overall survival was defined as the time from the date of the first treatment to the date of death, regardless of the cause of death.
For patients who were alive at the time of analysis, overall survival was censored at the last date the patient was known to be alive prior to the data cutoff date.
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From first treatment through September 27, 2010
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Improvement in Physical Symptoms (Improvement in Physician's Assessment of Global Performance Status and Oxygen Saturation Requirements, and Decrease in Total Dose and Frequency of Narcotic Pain Analgesics) During Treatment in Comparison to Baseline
Lasso di tempo: From first treatment through September 27, 2010
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Three parameters were measured.
(1) Improvement in the Physician's Assessment of Global Performance status on a 7-point scale (1=very much better to 7=very much worse).
(2) Improvement in oxygen saturation requirements, defined as a clinically meaningful increase in oxygen saturation requirement (from a baseline value < 95% to ≥ 95% saturation using a pulse oximeter).
(3) A decrease in total dose and frequency of narcotic pain analgesics.
The percentage of patients showing improvement (1 and 2) or a decrease (3) are reported.
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From first treatment through September 27, 2010
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Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15 of Cycle 1
Lasso di tempo: Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
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Blood samples for assessing the concentration of vemurafenib in plasma were drawn before the morning dose and at 2, 4, 6, and 8 hours post-dose on Day 15 of Cycle 1. Pharmacokinetic parameters were estimated by non-compartmental analysis (Win Non-Lin).
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Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
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Vemurafenib Plasma Level Area Under the Curve From 0 to 8 Hours (AUC0-8h) on Day 15 of Cycle 1
Lasso di tempo: Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
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Blood samples for assessing the concentration of vemurafenib in plasma were drawn before the morning dose and at 2, 4, 6, and 8 hours post-dose on Day 15 of Cycle 1. Pharmacokinetic parameters were estimated by non-compartmental analysis (Win Non-Lin).
AUC0-8h was calculated using the linear trapezoidal rule.
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Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
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Vemurafenib Plasma Levels at Various Treatment Cycles
Lasso di tempo: Pre-dose Cycle 1 Day 1 to 4 hours post-dose Cycle 10 Day 1
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Blood samples for assessing the concentration of vemurafenib in plasma were drawn before the morning dose and 4 hours post-dose at Day 1 of Cycles 1, 2, 3, 4, 6, 8, and 10.
Each Cycle was 3 weeks in duration.
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Pre-dose Cycle 1 Day 1 to 4 hours post-dose Cycle 10 Day 1
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Time-matched Change From Baseline in the Study Specific Corrected QT Interval (QTcP)
Lasso di tempo: Pre-dose Cycle 1 Day 1 to pre-dose Cycle 6 Day 1
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Three electrocardiograms (ECG) were obtained pre-dose and 2, 4, 6, and 8 hours post-dose at Days 1 and 15 of Cycle 1 and again pre-dose and 4 hours post-dose at various Cycles throughout treatment.
Five baseline triplicate ECGs were obtained before the start of treatment at the same time points used during treatment.
Reported is the largest mean time-matched QTcP change from baseline.
QTcP=QT/(60/heart rate)^β (β=mean [calculated separately for males and females] log-transformed QT versus log-transformed RR regression slopes using all available pre-treatment (baseline) ECG values.
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Pre-dose Cycle 1 Day 1 to pre-dose Cycle 6 Day 1
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Percentage of Patients With Adverse Event
Lasso di tempo: From first treatment through September 27, 2010
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The intensity of adverse events was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v 4.0 (CTCAE) on a 5-point scale (Grade 1 to 5: Mild, Moderate, Severe, Life-threatening, and Death).
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From first treatment through September 27, 2010
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
- Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, Chapman PB, Kim MJ, Hayward R, Martin M, Yang H, Wang Q, Hilton H, Hang JS, Noe J, Lambros M, Geyer F, Dhomen N, Niculescu-Duvaz I, Zambon A, Niculescu-Duvaz D, Preece N, Robert L, Otte NJ, Mok S, Kee D, Ma Y, Zhang C, Habets G, Burton EA, Wong B, Nguyen H, Kockx M, Andries L, Lestini B, Nolop KB, Lee RJ, Joe AK, Troy JL, Gonzalez R, Hutson TE, Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA, Lo RS, Ribas A, Marais R. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012 Jan 19;366(3):207-15. doi: 10.1056/NEJMoa1105358.
- Frederick DT, Salas Fragomeni RA, Schalck A, Ferreiro-Neira I, Hoff T, Cooper ZA, Haq R, Panka DJ, Kwong LN, Davies MA, Cusack JC, Flaherty KT, Fisher DE, Mier JW, Wargo JA, Sullivan RJ. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics. PLoS One. 2014 Jul 1;9(7):e101286. doi: 10.1371/journal.pone.0101286. eCollection 2014.
- Lacouture ME, Duvic M, Hauschild A, Prieto VG, Robert C, Schadendorf D, Kim CC, McCormack CJ, Myskowski PL, Spleiss O, Trunzer K, Su F, Nelson B, Nolop KB, Grippo JF, Lee RJ, Klimek MJ, Troy JL, Joe AK. Analysis of dermatologic events in vemurafenib-treated patients with melanoma. Oncologist. 2013;18(3):314-22. doi: 10.1634/theoncologist.2012-0333. Epub 2013 Mar 1.
- Ascierto PA, Ribas A, Larkin J, McArthur GA, Lewis KD, Hauschild A, Flaherty KT, McKenna E, Zhu Q, Mun Y, Dreno B. Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib +/- cobimetinib: a pooled analysis of four clinical trials. J Transl Med. 2020 Aug 3;18(1):294. doi: 10.1186/s12967-020-02458-x.
- Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, Hersey P, Kefford R, Lawrence D, Puzanov I, Lewis KD, Amaravadi RK, Chmielowski B, Lawrence HJ, Shyr Y, Ye F, Li J, Nolop KB, Lee RJ, Joe AK, Ribas A. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012 Feb 23;366(8):707-14. doi: 10.1056/NEJMoa1112302.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Effettivo)
30 settembre 2009
Completamento primario (Effettivo)
27 settembre 2010
Completamento dello studio (Effettivo)
3 giugno 2014
Date di iscrizione allo studio
Primo inviato
28 luglio 2009
Primo inviato che soddisfa i criteri di controllo qualità
29 luglio 2009
Primo Inserito (Stima)
30 luglio 2009
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
25 luglio 2017
Ultimo aggiornamento inviato che soddisfa i criteri QC
26 giugno 2017
Ultimo verificato
1 giugno 2017
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Neoplasie per tipo istologico
- Neoplasie
- Tumori neuroectodermici
- Neoplasie, cellule germinali ed embrionali
- Neoplasie, tessuto nervoso
- Tumori neuroendocrini
- Nevi e melanomi
- Melanoma
- Meccanismi molecolari dell'azione farmacologica
- Inibitori enzimatici
- Agenti antineoplastici
- Inibitori della chinasi proteica
- Vemurafenib
Altri numeri di identificazione dello studio
- NP22657
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su vemurafenib
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Inova Health Care ServicesGenentech, Inc.Ritirato
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Hoffmann-La RocheTerminatoMelanoma malignoStati Uniti, Francia, Australia, Regno Unito, Italia, Spagna, Germania, Israele, Polonia, Slovacchia
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Mohammed M MilhemGenentech, Inc.TerminatoMelanoma | Melanoma metastatico | Melanoma metastatico con mutazione BRAF | Melanoma metastatico con mutazione V600EBRAFStati Uniti
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Center Eugene MarquisCompletato
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Shanghai Kechow Pharma, Inc.Non ancora reclutamentoCarcinoma polmonare non a piccole cellule
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Daiichi Sankyo, Inc.PlexxikonTerminatoMelanoma non resecabile BRAF con mutazione V600 | Melanoma metastatico BRAF mutato V600 | Melanoma metastatico di stadio III o IV che non è stato precedentemente trattato con un inibitore selettivo di BRAFStati Uniti, Germania, Francia
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Celldex TherapeuticsMemorial Sloan Kettering Cancer CenterCompletato
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M.D. Anderson Cancer CenterGenentech, Inc.Attivo, non reclutanteCancro alla tiroideStati Uniti
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Radboud University Medical CenterThe Netherlands Cancer Institute; IsalaReclutamentoMelanoma, maligno, delle parti molliOlanda
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Grupo Español Multidisciplinar de MelanomaRoche Farma, S.A; Pivotal S.L.Completato