1421TiP - A randomized double-blind phase II study evaluating the role of maintenance therapy with cabozantinib in high grade undifferentiated uterine sarcom...

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Soft Tissue Sarcomas
Surgical oncology
Therapy
Radiation oncology
Presenter Isabelle Ray-Coquard
Citation Annals of Oncology (2016) 27 (6): 483-492. 10.1093/annonc/mdw388
Authors I.L. Ray-Coquard1, A.P. Dei Tos2, C. Coens3, M. Huizing4, A. Casado Herraez5, A.M. Westermann6, E. Bompas7, H. Earl8, M.L. Hensley9, A. Negrouk10, N. Reed11
  • 1Département D'oncologie Médicale Adulte, Centre Léon Bérard, 69008 - Lyon/FR
  • 2Department Of Pathology, Ospedale Regionale Ca' Foncello, 31100 - Treviso/IT
  • 3Quality Of Life Department, European Organisation for Research and Treatment of Cancer, 1200 - Brussels/BE
  • 4Moca, U.Z.A. University Hospital Antwerp, Edegem/BE
  • 5Department Of Medical Oncology, Hospital Clinico Universitario San Carlos, 28040 - Madrid/ES
  • 6Medical Oncology F4-224, Academic Medical Center (AMC), 1105AZ - Amsterdam/NL
  • 74-department Of Medical Oncology, Institut de cancérologie de l'Ouest - René Gauducheau, 44805 - Saint-Herblain/FR
  • 8Oncology, Addenbrooke's Hospital University of Cambridge Hospitals, CB2 0QQ - Cambridge/GB
  • 9Medical Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 10International Regulatory And Intergroup Unit, European Organisation for Research and Treatment of Cancer (EORTC), 1200 - Brussels/BE
  • 11Beatson Oncology Centre, Gartnavel General Hospital, G12 0YN - Glasgow/GB

Abstract

Background

HGUS accounts for 6% of all uterine sarcomas and has a very poor prognosis. Most patients (pts) die of recurrent disease within 1 year of diagnosis. Treatment recommendations for advanced stage include chemotherapy with anthracyclines +/- ifosfamide, although data for the efficacy of these agents in this histologic subtype are very limited. Recently vascular invasion reported to be a driver of the progression for such sarcoma subtype suggesting anti-angiogenics and so cabozantinib (VEGFR2/c-MET inhibitor) potentially active for HGUS.

Trial design

This randomized phase II double-blinded trial aims to measure the role of maintenance therapy with cabozantinib in HGUS after stabilization (SD) or response (Complete Response (CR) + Partial Response (PR)) to doxorubicin-based chemotherapy following surgery or in metastatic 1st line treatment. The main objective of the trial is to assess the efficacy of maintenance treatment with cabozantinib compared with placebo. Approximately 54 pts will be randomized, after central pathological review, to cabozantinib 60 mg once daily or placebo for up to 24 months, to detect an improvement in progression free survival (PFS) rate at 4 months from 50% to 80% with a one-sided 15% significance level. Pts randomized to the placebo arm may cross-over to cabozantinib at the time of progression. This trial is a cooperation between European Organisation for Research and Treatment of Cancer (EORTC), Cancer Research UK (CRUK) and National Cancer Institute (NCI, US) and is part of the International Rare Cancers Initiative (IRCI). Primary objective: PFS rate at 4 months according to RECIST 1.1 Secondary objectives: PFS, Overall Survival, Safety, Response Rate and duration of response Study status: The first pts from EORTC (6 participating countries) was randomized in Feb 2015. As of 6 May 2016, 15 and 5 pts have been registered and randomized after central pathology confirmation of HGUS, respectively. CRUK has started recruitment in May 2016 and NRG Oncology in US is expected to start in October 2016.

Clinical trial identification

NCT number: NCT01979393; EudraCT: 2013-000762-11

Legal entity responsible for the study

European Organisation for Research and Treatment of Cancer (EORTC)

Funding

European Organisation for Research and Treatment of Cancer (EORTC)

Disclosure

All authors have declared no conflicts of interest.