Poster display

3614 - A randomized double-blind phase II study evaluating the role of maintenance therapy with cabozantinib in high grade undifferentiated uterine sarcoma (HGUS) after stabilization or response to doxorubicin +/- ifosfamide following surgery or in metastatic first line treatment

Date

10 Oct 2016

Session

Poster display

Presenters

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

Author affiliations

¹ Département D'oncologie Médicale Adulte, Centre Léon Bérard, 69008 - Lyon/FR
² Department Of Pathology, Ospedale Regionale Ca' Foncello, 31100 - Treviso/IT
³ Quality Of Life Department, European Organisation for Research and Treatment of Cancer, 1200 - Brussels/BE
⁴ Moca, U.Z.A. University Hospital Antwerp, Edegem/BE
⁵ Department Of Medical Oncology, Hospital Clinico Universitario San Carlos, 28040 - Madrid/ES
⁶ Medical Oncology F4-224, Academic Medical Center (AMC), 1105AZ - Amsterdam/NL
⁷ 4-department Of Medical Oncology, Institut de cancérologie de l'Ouest - René Gauducheau, 44805 - Saint-Herblain/FR
⁸ Oncology, Addenbrooke's Hospital University of Cambridge Hospitals, CB2 0QQ - Cambridge/GB
⁹ Medical Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
¹⁰ International Regulatory And Intergroup Unit, European Organisation for Research and Treatment of Cancer (EORTC), 1200 - Brussels/BE
¹¹ Beatson Oncology Centre, Gartnavel General Hospital, G12 0YN - Glasgow/GB

Resources

Abstract 3614

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 1^st 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