IRCI Gynae Sarcomas, High Grade Uterine Sarcoma

• ClinicalTrials.gov Identifier: NCT01979393
• Recruitment Status: Recruiting
• First Posted: November 8, 2013
• Last Update Posted: January 31, 2020
• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborators: Gynecologic Oncology Group; NHS Greater Glasgow and Clyde
• Information provided by (Responsible Party): European Organisation for Research and Treatment of Cancer - EORTC

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Uterine Sarcoma	Drug: Cabozantinib; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 78 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Double-blind Phase II Study Evaluating the Role of Maintenance Therapy With Cabozantinib in High Grade Undifferentiated Uterine Sarcoma (HGUS) After Stabilization or Response to Doxorubicin +/- Ifosfamide Following Surgery or in Metastatic First Line Treatment
• Study Start Date: February 2015
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: December 2021

Arms and Interventions

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: Cabozantinib; Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: 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 :

1. Progression free survival [ Time Frame: 3.5 years from first patient in ]
2. Overall survival [ Time Frame: 3.5 years from first patient in ]
3. Response rate [ Time Frame: 3.5 years from first patient in ]
4. Duration of response to cabozantinib [ Time Frame: 3.5 years from first patient in ]
5. Response rate to anthracycline-based chemotherapy for the patients with measurable disease [ Time Frame: 3.5 years from first patient in ]
6. Assessment of global health status/QoL scale [ Time Frame: 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
7. Occurence of Adverse Events [ Time Frame: 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.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Locally advanced: newly diagnosed HGUS with advanced disease (stage III or stage IV) or residual disease after primary surgery
• 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
• 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 sarcoma (ESS & leiomyosarcoma), leiomyosarcoma (intermediate & high grade), carcinosarcoma, adenosarcoma, rhabdomyosarcoma (alveolar or embryonal) and soft tissue Primitive Neuroectodermal Tumors 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

Contacts and Locations

Contacts

Contact: Ellen Peeters; +32 2 7741082; ellen.peeters@eortc.be

Contact: Vinciane Vinckx; +32 2 7741032; vinciane.vinckx@eortc.be

Locations

Belgium

Universitair Ziekenhuis Antwerpen; Recruiting

Edegem, Belgium

Principal Investigator: Manon Huizing

France

Institut Bergonie; Recruiting

Bordeaux, France, 33076

Contact: Contact Person 33-556-333-333

Principal Investigator: Anne Floquet

Centre Georges-Francois-Leclerc; Recruiting

Dijon, France, 21079

Principal Investigator: Nicolas Isambert

Centre Leon Berard; Recruiting

Lyon, France, 69373

Contact: Contact Person 33-4-7878-2645

Principal Investigator: Isabelle Ray-Coquard

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

Nantes, France

Principal Investigator: Emmanualle Bompas

Italy

Fondazione IRCCS Istituto Nazionale dei Tumori; Recruiting

Milano, Italy, 20133

Principal Investigator: Paolo Casali

Netherlands

Academisch Medisch Centrum at University of Amsterdam; Recruiting

Amsterdam, Netherlands, 1105 AZ

Principal Investigator: Anneke Westermann, MD

Spain

Hospital General Vall D'Hebron; Recruiting

Barcelona, Spain, 08035

Principal Investigator: Claudia Valverde

Hospital Universitario San Carlos; Recruiting

Madrid, Spain, 28040

Principal Investigator: Antonio Casado

United Kingdom

Cambridge University Hospital NHS - Addenbrookes Hospital; Recruiting

Cambridge, United Kingdom

Principal Investigator: Helena Earl

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

Glasgow, United Kingdom

Principal Investigator: Nick Reed

Sponsors and Collaborators

European Organisation for Research and Treatment of Cancer - EORTC

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
• ClinicalTrials.gov Identifier: NCT01979393
• Other Study ID Numbers: EORTC-62113-55115; 2013-000762-11 ( EudraCT Number ); UC1306 ( Other Identifier: GOG )
• First Posted: November 8, 2013
• Last Update Posted: January 31, 2020
• Last Verified: January 2020

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:

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

Additional relevant MeSH terms:

Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms