Clinical trial NCT01979393: IRCI Gynae Sarcomas, High Grade Uterine Sarcoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Uterine Sarcoma
Keywords: Locally advanced
stage III
stage IV
residual disease after primary surgery
newly diagnosed HGUS
Metastatic
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Gynecologic Oncology Group
name: NHS Greater Glasgow and Clyde
First posted: 2013-11-08
Enrollment: 58
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 3.5 years from first patient in
Secondary outcomes:
measure: Progression free survival
timeFrame: 3.5 years from first patient in
measure: Overall survival
timeFrame: 3.5 years from first patient in
measure: Response rate
timeFrame: 3.5 years from first patient in
measure: Duration of response to cabozantinib
timeFrame: 3.5 years from first patient in
measure: Response rate to anthracycline-based chemotherapy for the patients with measurable disease
timeFrame: 3.5 years from first patient in
measure: Assessment of global health status/QoL scale
timeFrame: 3.5 years from first patient in
measure: Occurence of Adverse Events
timeFrame: 3.5 years from first patient in
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Leon Berard
city: Nantes
country: France
facility: Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
city: Barcelona
country: Spain
facility: Hospital General Vall D'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospital NHS - Addenbrookes Hospital
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust - St. James's University Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust - University College Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust - City Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust - Churchill Hospital
Study officials:
affiliation: Centre Léon Bérard, Lyon, France
name: Isabelle Ray-Coquard, MD
role: STUDY_CHAIR
affiliation: NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre - Gartnavel General Hospital , Glasgow, United Kingdom
name: Nicholas Reed, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.