IRCI Gynae Sarcomas, High Grade Uterine Sarcoma

A Randomized Double-blind Phase II Study Evaluating the Role of Maintenance Therapy With Cabozantinib in High Grade Uterine Sarcoma (HGUtS) After Stabilization or Response to Doxorubicin +/- Ifosfamide Following Surgery or in Metastatic First Line Treatment

This study aims to investigate a drug called Cabozantinib which belongs to a family of drugs that have effects on tumour growth, blood supply, invasion and spread.

Therefore, we want to find out whether taking cabozantinib after treatment with surgery and chemotherapy is effective and safe for patients who responded or had stable disease after their chemotherapy.

All participants will receive 4-6 cycles of standard chemotherapy. Those with stabilization or response to the standard chemotherapy will be split into 2 groups (cabozantinib or placebo).

Study Overview

• Status: Completed
• Conditions: Uterine Sarcoma
• Intervention / Treatment: Drug: Placebo; Drug: Cabozantinib

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Bordeaux, France
    • Institut Bergonie
  • Lyon, France, 69373
    • Centre Leon Berard
  • Nantes, France
    • Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau
• Italy
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum at University of Amsterdam
• Spain
  • Barcelona, Spain, 08035
    • Hospital General Vall D'Hebron
  • Madrid, Spain, 28040
    • Hospital Universitario San Carlos
• United Kingdom
  • Cambridge, United Kingdom
    • Cambridge University Hospital NHS - Addenbrookes Hospital
  • Glasgow, United Kingdom
    • NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
  • Leeds, United Kingdom
    • Leeds Teaching Hospitals NHS Trust - St. James's University Hospital
  • London, United Kingdom
    • University College London Hospitals NHS Foundation Trust - University College Hospital
  • London, United Kingdom
    • Royal Marsden Hospital
  • Nottingham, United Kingdom
    • Nottingham University Hospitals NHS Trust - City Hospital
  • Oxford, United Kingdom
    • Oxford University Hospitals NHS Trust - Churchill Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who are suitable for treatment with doxorubicin +/- ifosfamide and fall within one of the following patient populations:

  • HGUS, HGESS, HGLMS and HG adenosarcoma

  • FIGO stage II and stage III : if adjuvant chemotherapy is proposed
  • FIGO stage IV: if first line chemotherapy is proposed
• Metastatic: diagnosed with disease relapse after local treatment for primary tumor
• at least 18 years old
• written informed consent
• Central pathological confirmation: Histological evidence of HGUS, HGESS, HGLMS and HG adenosarcoma
• Non-progressive patients (CR, PR, SD) at the end of the first line treatment (standard chemotherapy consisting of 4 to 6 cycles of anthracyclines alone or in combination with ifosfamide)
• WHO/ECOG performance status 0-2
• Adequate organ and bone marrow function within 3 days prior to the first dose of study treatment (Cabozantinib/placebo)
• Clinically normal cardiac function
• Women of child bearing potential must have a negative serum/urine pregnancy test within 3 days prior to the first dose of study treatment
• Adequate birth control measures

Exclusion Criteria:

• low-grade ESS, leiomyosarcoma (low or intermediate), carcinosarcoma, low-grade adenosarcoma, rhabdomyosarcoma (alveolar or embryonal) and soft tissue PNET of uterus/cervix.
• contraindications to cabozantinib
• not able to swallow and retain oral tablets
• planned use of chemotherapy, radiation therapy, radionuclide treatment, small molecule tyrosine kinase inhibitor or hormonal therapy, and any other investigational agent (Cabozantinib/placebo) during the treatment period
• concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
• patient with poorly controlled hypertension defined at baseline as blood pressure >150/90
• patients who have suffered a cerebrovascular accident at any time in the past, patients who have suffered a transient ischemic attack in the past 6 months, patients who have suffered a deep venous thrombosis (DVT) or a pulmonary embolism in the past 6 months
• Gastrointestinal disorders
• patients with radiographic evidence of cavitating pulmonary lesion(s)
• patients with tumor in contact with, invading or encasing any major blood vessels
• patients evidence of tumor invading the GI tract
• evidence of active bleeding or bleeding diathesis
• hemoptysis ≥ 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose of study treatment
• signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
• clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
• prior major surgery or trauma within 6 weeks prior to first dose of study drug and any wound, fracture, or ulcer should be completely healed
• concurrent or planned treatment with strong inhibitors or inducers of cytochrome P450 3A4/5

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cabozantinib; Cabozantinib maintenance 60 mg daily for 2 years or until withdrawal criterion After documented disease progression (according to RECIST 1.1), the treatment will be unblinded. Subjects receiving cabozantinib shall be further treated at the investigator discretion.	Drug: Cabozantinib
Experimental: Placebo; Placebo daily for 2 years or until withdrawal criterion. After documented disease progression (according to RECIST 1.1), the treatment will be unblinded. Subjects receiving placebo shall be offered the option of receiving cabozantinib up to further progression. This is not mandatory and treatment is at the investigator decision.	Drug: Placebo; Drug: Cabozantinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	The primary endpoint is PFS rate at 4 months after randomization to cabozantinib or placebo	3.5 years from first patient in

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival		3.5 years from first patient in
Overall survival		3.5 years from first patient in
Response rate		3.5 years from first patient in
Duration of response to cabozantinib		3.5 years from first patient in
Response rate to anthracycline-based chemotherapy for the patients with measurable disease		3.5 years from first patient in
Assessment of global health status/QoL scale	The primary health-related quality of life endpoint that is considered of interest for this study is the global health status/QoL scale	3.5 years from first patient in
Occurence of Adverse Events	This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, for adverse event reporting.	3.5 years from first patient in

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborators: Gynecologic Oncology Group; NHS Greater Glasgow and Clyde
• Investigators: Study Chair: Isabelle Ray-Coquard, MD, Centre Léon Bérard, Lyon, France; Principal Investigator: Nicholas Reed, MD, NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital , Glasgow, United Kingdom

Publications and helpful links

General Publications

• Ray-Coquard I, Hatcher H, Bompas E, Casado A, Westermann A, Isambert N, Casali PG, Pratap S, Stark D, Valverde C, Anand A, Huizing M, Floquet A, Lindner L, Hermes B, Seddon B, Coens C, Jones R, Reed N. 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). Int J Gynecol Cancer. 2020 Oct;30(10):1633-1637. doi: 10.1136/ijgc-2020-001519. Epub 2020 Jun 15.
• Hanvic B, Ray-Coquard I. Gynecological sarcomas: literature review of 2020. Curr Opin Oncol. 2021 Jul 1;33(4):345-350. doi: 10.1097/CCO.0000000000000753.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2015
• Primary Completion (Actual): May 18, 2022
• Study Completion (Actual): January 15, 2024

Study Registration Dates

• First Submitted: November 4, 2013
• First Submitted That Met QC Criteria: November 4, 2013
• First Posted (Estimated): November 8, 2013

Study Record Updates

• Last Update Posted (Actual): August 1, 2025
• Last Update Submitted That Met QC Criteria: July 30, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: stage III; Metastatic; Locally advanced; stage IV; residual disease after primary surgery; newly diagnosed HGUS
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Sarcoma
• Other Study ID Numbers: EORTC-62113-55115; 2013-000762-11 (EudraCT Number); UC1306 (Other Identifier: GOG)