Efficacy and Safety of RAD001 (Everolimus) in Patients Affected by Biliary Tract Cancer Progressing after Prior Chemiotherapy: a Phase II I.T.M.O. Study

Nel dicembre 2008 è stato avviato uno studio sul carcinoma delle vie biliari.

Lo studio  (Protocollo N°02/2008) ha l’obiettivo di valutare l’efficacia e la tollerabilità  di RAD 001 (Everolimus ) in pazienti affetti da carcinoma delle vie biliari intra ed extra epatiche in progressione dopo chemioterapia di prima linea.

Lo studio è stato chiuso al reclutamento nel febbraio 2010. Sono stati  arruolati 39 pazienti.
Centri partecipanti :

  • Fondazione IRCCS Istituto Nazionale Tumori, MILANO
  • ASL 1 Ospedale di CARRARA
  • Ospedale Civile di SONDRIO
  • Az. Ospedaliera Carlo Poma, MANTOVA
  • Ospedale Maggiore della Carità di NOVARA
  • Ospedale Misericordia e Dolce, PRATO
  • Presidio Ospedaliero di GORGONZOLA (MI)

Riferimento Bibliografico:

  • Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: a phase II ITMO study.
    (Buzzoni R, Pusceddu S, Bajetta E, De Braud F, Platania M, Iannacone C, Cantore M, Mambrini A, Bertolini A, Alabiso O, Ciarlo A, Turco C, Mazzaferro V).
    Ann Oncol. 2014 Aug;25(8):1597-603. doi: 10.1093/annonc/mdu175. Epub 2014 May 14.


Biliary tract cancer (BTC) is a highly lethal disease for which the best available therapy remains undetermined. The mammalian target of rapamycin (mTOR) pathway is up-regulated in several cancers, including BTC, and preclinical evidence indicates that mTOR inhibition may be effective in the treatment of BTC. We sought to evaluate the activity and tolerability of the mTOR inhibitor RAD001-everolimus-in patients with BTC progressing after prior chemotherapy.

This was an open-label, single-arm, phase II study (EUDRACT 2008-007152-94) conducted in eight sites in Italy. Patients with locally advanced, metastatic or recurrent BTC progressing despite previous chemotherapy received a daily oral dose of everolimus 10 mg administered continuously in 28-day cycles. The two primary end points were disease control rate (DCR) and objective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival (OS) and time-to-progression (TTP).

Thirty-nine patients were enrolled. The DCR was 44.7%, and the ORR was 5.1%. One patient showed a partial response at 2 months and one patient showed a complete response sustained up to 8 months. The median (95% confidence interval) PFS was 3.2 (1.8-4.0) months, and the median OS was 7.7 (5.5-13.2) months. The median TTP was 2.0 (1.7-3.7) months. Most common toxicities were asthenia (43.6%), thrombocytopenia (35.9%), pyrexia (30.8%) and erythema, mainly of mild-to-moderate severity. Two patients required dose reduction due to adverse events.

Everolimus demonstrated a favourable toxicity profile and encouraging anti-tumour activity. Further trials are needed to establish the role of everolimus in the treatment of BTC. EUDRACT 2008-007152-94.

advanced biliary tract cancer; everolimus; mTOR

PMID: 24827133   [PubMed – in process]

Download articolo: Annals of Oncology 2014