IRCI Gynae Sarcomas, High Grade Uterine Sarcoma

Uterine Sarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01979393
• Other study ID #: EORTC-62113-55115
• Secondary ID: 2013-000762-11UC
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 2015
• Est. completion date: May 2024

Study information

• Verified date: February 2024
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 58
• Est. completion date: May 2024
• Est. primary completion date: March 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sarcoma
• Uterine Sarcoma

Intervention

Drug:
• Cabozantinib

• Placebo

Locations

Country	Name	City	State
France	Institut Bergonie	Bordeaux
France	Institut Bergonie	Bordeaux
France	Centre Leon Berard	Lyon
France	Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau	Nantes
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Netherlands	Academisch Medisch Centrum at University of Amsterdam	Amsterdam
Spain	Hospital General Vall D'Hebron	Barcelona
Spain	Hospital Universitario San Carlos	Madrid
United Kingdom	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	Royal Marsden Hospital	London
United Kingdom	University College London Hospitals NHS Foundation Trust - University College Hospital	London
United Kingdom	Nottingham University Hospitals NHS Trust - City Hospital	Nottingham
United Kingdom	Oxford University Hospitals NHS Trust - Churchill Hospital	Oxford

Sponsors (3)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Gynecologic Oncology Group, NHS Greater Glasgow and Clyde

Countries where clinical trial is conducted

France,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression free survival		3.5 years from first patient in
Secondary	Overall survival		3.5 years from first patient in
Secondary	Response rate		3.5 years from first patient in
Secondary	Duration of response to cabozantinib		3.5 years from first patient in
Secondary	Response rate to anthracycline-based chemotherapy for the patients with measurable disease		3.5 years from first patient in
Secondary	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
Secondary	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