IRCI Gynae Sarcomas, High Grade Uterine Sarcoma

Phase 2

Active, not recruiting

• Conditions: Uterine Sarcoma
• Interventions: Drug: Cabozantinib; Drug: Placebo

• Registration Number: NCT01979393
• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-11-04
• Study First Submitted QC: 2013-11-04
• Study First Posted: 2013-11-08
• Study Start: 2015-02
• Primary Completion: 2022-03
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-05
• Last Update Posted: 2024-02-06
• Study Completion: 2024-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 58

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cabozantinib	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.
Placebo	Cabozantinib	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.
Placebo	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	3.5 years from first patient in	The primary health-related quality of life endpoint that is considered of interest for this study is the global health status/QoL scale
Occurence of Adverse Events	3.5 years from first patient in	This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, for adverse event reporting.

Trial Locations

Locations (14)

Academisch Medisch Centrum at University of Amsterdam; 🇳🇱 Amsterdam, Netherlands

Centre Leon Berard; 🇫🇷 Lyon, France

Hospital Universitario San Carlos; 🇪🇸 Madrid, Spain

University College London Hospitals NHS Foundation Trust - University College Hospital; 🇬🇧 London, United Kingdom

Royal Marsden Hospital; 🇬🇧 London, United Kingdom

Oxford University Hospitals NHS Trust - Churchill Hospital; 🇬🇧 Oxford, United Kingdom

Nottingham University Hospitals NHS Trust - City Hospital; 🇬🇧 Nottingham, United Kingdom

Institut Bergonie; 🇫🇷 Bordeaux, France

Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau; 🇫🇷 Nantes, France

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milano, Italy

Hospital General Vall D'Hebron; 🇪🇸 Barcelona, Spain

Cambridge University Hospital NHS - Addenbrookes Hospital; 🇬🇧 Cambridge, United Kingdom

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

Leeds Teaching Hospitals NHS Trust - St. James's University Hospital; 🇬🇧 Leeds, United Kingdom