A randomized double-blind phase II study evaluating the role of maintenance therapy with cabozantinib in high-grade uterine sarcoma after stabilization or response to doxorubicin ± ifosfamide following surgery or in metastatic first line treatment (EORTC62113).


Journal

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
ISSN: 1525-1438
Titre abrégé: Int J Gynecol Cancer
Pays: England
ID NLM: 9111626

Informations de publication

Date de publication:
10 2020
Historique:
accepted: 08 05 2020
pubmed: 18 6 2020
medline: 9 11 2021
entrez: 18 6 2020
Statut: ppublish

Résumé

Uterine sarcomas are a group of rare tumors that include different subtypes. Patients with histopathological high-grade diseases are at high-risk of recurrence or progression, and have a poor prognosis. We aim to explore the most appropriate management in patients with uterine high-grade sarcomas. To assess the efficacy of maintenance treatment with cabozantinib in patients with high-grade uterine sarcomas who achieved clinical benefit after standard chemotherapy. Maintenance treatment with cabozantinib after standard chemotherapy given as an adjuvant treatment after curative surgery, or in locally advanced or metastatic disease, increases progression-free survival compared with placebo TRIAL DESIGN: This is a randomized double blinded phase II trial. The study is enrolling adult patients with high-grade undifferentiated uterine sarcomas, high-grade endometrial stromal sarcomas, high-grade leiomyosarcoma, and high-grade adenosarcoma, FIGO (Federation International gynecologue Obstétricien) stage II/III to IV in stable disease or who achieved complete or partial response with doxorubicin ± ifosfamide, who are assigned 1:1 to 60 mg daily cabozantinib (experimental arm) or placebo (control arm), as maintenance therapy. Exclusion criteria include low-grade sarcoma. Progression-free survival at 4 months. The study plans to enroll 90 patients to allow the randomization of 54 patients to detect an improvement in 4-month progression-free survival from 50% to 80% with 15% significance level and 85% power. Estimated dates for accrual completion: recruitment for the trial started in February 2015, and has currently enrolled 83 patients, of whom 35 patients have been randomized. The end of recruitment is anticipated for December 2020. ClinicalTrials.gov, number NCT01979393.

Sections du résumé

BACKGROUND
Uterine sarcomas are a group of rare tumors that include different subtypes. Patients with histopathological high-grade diseases are at high-risk of recurrence or progression, and have a poor prognosis. We aim to explore the most appropriate management in patients with uterine high-grade sarcomas.
PRIMARY OBJECTIVE
To assess the efficacy of maintenance treatment with cabozantinib in patients with high-grade uterine sarcomas who achieved clinical benefit after standard chemotherapy.
STUDY HYPOTHESIS
Maintenance treatment with cabozantinib after standard chemotherapy given as an adjuvant treatment after curative surgery, or in locally advanced or metastatic disease, increases progression-free survival compared with placebo TRIAL DESIGN: This is a randomized double blinded phase II trial.
MAJOR INCLUSION/EXCLUSION CRITERIA
The study is enrolling adult patients with high-grade undifferentiated uterine sarcomas, high-grade endometrial stromal sarcomas, high-grade leiomyosarcoma, and high-grade adenosarcoma, FIGO (Federation International gynecologue Obstétricien) stage II/III to IV in stable disease or who achieved complete or partial response with doxorubicin ± ifosfamide, who are assigned 1:1 to 60 mg daily cabozantinib (experimental arm) or placebo (control arm), as maintenance therapy. Exclusion criteria include low-grade sarcoma.
PRIMARY ENDPOINT
Progression-free survival at 4 months.
SAMPLE SIZE
The study plans to enroll 90 patients to allow the randomization of 54 patients to detect an improvement in 4-month progression-free survival from 50% to 80% with 15% significance level and 85% power. Estimated dates for accrual completion: recruitment for the trial started in February 2015, and has currently enrolled 83 patients, of whom 35 patients have been randomized. The end of recruitment is anticipated for December 2020.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov, number NCT01979393.

Identifiants

pubmed: 32546554
pii: ijgc-2020-001519
doi: 10.1136/ijgc-2020-001519
doi:

Substances chimiques

Anilides 0
Pyridines 0
cabozantinib 1C39JW444G
Doxorubicin 80168379AG

Banques de données

ClinicalTrials.gov
['NCT01979393']

Types de publication

Clinical Trial Protocol Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1633-1637

Informations de copyright

© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Isabelle Ray-Coquard (I)

Centre Leon Berard, Lyon, Rhône-Alpes, France isabelle.ray-coquard@lyon.unicancer.fr.
Oncology, Université Claude Bernard Lyon 1, Villeurbanne, Auvergne-Rhône-Alpes, France.

Helen Hatcher (H)

medical oncology, Cambridge University, Cambridge, Cambridgeshire, UK.

Emmanuelle Bompas (E)

Medical Oncology Department, ICO, Saint Herblain, Pays de la Loire, France.

Antonio Casado (A)

Medical Oncology Department, Complutense University of Madrid, Madrid, Comunidad de Madrid, Spain.

Annekke Westermann (A)

Medical Oncology Department, Academisch Medisch Centrum, Amsterdam, North Holland, The Netherlands.

Nicolas Isambert (N)

Medical Oncology Department, Centre Georges-François Leclerc, Dijon, Bourgogne-Franche-Comté, France.

Paolo Giovanni Casali (PG)

Medical Oncology Department, IRCCS, Milano, Lombardia, Italy.

Sarah Pratap (S)

Medical Oncology Department, Oxford University, Oxford, Oxfordshire, UK.

Daniel Stark (D)

Medical Oncology Department, Leeds Teaching Hospitals NHS Trust, Leeds, Leeds, UK.

Claudia Valverde (C)

Medical Oncology Department, Vall d'Hebron Hospital, Barcelona, Catalunya, Spain.

Anjana Anand (A)

Medical Oncology Department, Nottingham Trent University, Nottingham, Nottinghamshire, UK.

Manon Huizing (M)

Medical Oncology Department, Universitair Ziekenhuis Antwerpen, Edegem, Antwerp, Belgium.

Anne Floquet (A)

Medical Oncology Department, Institut Bergonié, Bordeaux, Aquitaine, France.

Lars Lindner (L)

Medical Oncology Department, Ludwig-Maximilians-Universitat Munchen, Munchen, Bayern, Germany.

Barbara Hermes (B)

Medical Oncology Department, Eberhard Karls Universitat Tubingen, Tubingen, Baden-Württemberg, Germany.

Beatrice Seddon (B)

Medical Oncology Department, University College London, London, London, UK.

Corneel Coens (C)

Statistics and Quality of Life, EORTC, Brussels, Belgium.

Robin Jones (R)

Medical Oncology, Royal Marsden Hospital NHS Trust, London, London, UK.

Nick Reed (N)

Medical Oncology, NHS Greater Glasgow and Clyde, Glasgow, Glasgow, UK.

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Classifications MeSH