IRCI Gynae Sarcomas, High Grade Uterine Sarcoma

NCT01979393 | Completed Phase 2 DMC

• 3 other identifiers: EORTC-62113-551152013-000762-11UC1306
• Study Type: interventional
• Target: 58
• Locations: 5 countries
• Sites: 15

Brief Summary

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).

Conditions

Uterine Sarcoma

Keywords

Locally advanced; stage III; stage IV; residual disease after primary surgery; newly diagnosed HGUS; Metastatic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

Study Arms (2)

Cabozantinib

EXPERIMENTAL

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

Placebo

EXPERIMENTAL

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: Cabozantinib; Drug: Placebo

Interventions

Cabozantinib DRUG

Cabozantinib; Placebo

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Gynecologic Oncology Group: collaborator
• NHS Greater Glasgow and Clyde: collaborator

Study Sites (15)

Institut Bergonie

Bordeaux, 33076, France

Location

Institut Bergonie

Bordeaux, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau

Nantes, France

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Academisch Medisch Centrum at University of Amsterdam

Amsterdam, 1105 AZ, Netherlands

Location

Hospital General Vall D'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario San Carlos

Madrid, 28040, Spain

Location

Cambridge University Hospital NHS - Addenbrookes Hospital

Cambridge, United Kingdom

Location

NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital

Glasgow, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust - St. James's University Hospital

Leeds, United Kingdom

Location

Royal Marsden Hospital

London, United Kingdom

Location

University College London Hospitals NHS Foundation Trust - University College Hospital

London, United Kingdom

Location

Nottingham University Hospitals NHS Trust - City Hospital

Nottingham, United Kingdom

Location

Oxford University Hospitals NHS Trust - Churchill Hospital

Oxford, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 34009140 DERIVED

• 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.

  PMID: 32546554 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Isabelle Ray-Coquard, MD

  Centre Léon Bérard, Lyon, France

  STUDY CHAIR

• Nicholas Reed, MD

  NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital , Glasgow, United Kingdom

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2013
• First Posted: November 8, 2013
• Study Start: February 2, 2015
• Primary Completion: May 18, 2022
• Study Completion: January 15, 2024
• Last Updated: August 1, 2025

Record last verified: 2025-07

Locations

NL (1); ES (2); IT (1); FR (4); GB (7)