Clinical trial • Phase III • Oncology

cabozantinib for Metastatic renal cell carcinoma

Phase III trial of cabozantinib for Metastatic renal cell carcinoma.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Metastatic renal cell carcinoma
Trial Stage
Phase III
Drug Modality
Small molecule | Monoclonal antibody

Key dates

Initial CTIS Submission Date
16-09-2024
First CTIS Authorization Date
14-10-2024

Trial design

Randomised, control arm: nivolumab + ipilimumab (nivolumab: dose unit mg/kg, maxdailydoseamount 3 mg/kg iv; ipilimumab: dose unit mg/kg, maxdailydoseamount 1 mg/kg iv). experimental arm: cabozantinib (cabometyx 20 mg film-coated tablets; dose unit mg, maxdailydoseamount 40 mg oral) in combination with nivolumab and ipilimumab. Phase III trial across 47 sites in Belgium, Czechia, Finland and others.

Randomised
Yes
Comparator
Control arm: Nivolumab + Ipilimumab (Nivolumab: dose unit mg/kg, maxDailyDoseAmount 3 mg/kg IV; Ipilimumab: dose unit mg/kg, maxDailyDoseAmount 1 mg/kg IV). Experimental arm: Cabozantinib (CABOMETYX 20 mg film-coated tablets; dose unit mg, maxDailyDoseAmount 40 mg oral) in combination with Nivolumab and Ipilimumab.
Target Sample Size
517

Eligibility

Recruits 517 adults.

Inclusion criteria

  • {"criterion_text":"- 1. Histologically confirmed advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) renal cell carcinoma with a clear-cell component.\n- 2. Intermediate- or poor-risk RCC as defined by International Metastatic RCC Database Consortium (IMDC) criteria.\n- 3. Measurable disease per RECIST 1.1 as determined by the Investigator.\n- 4. Karnofsky Performance Status (KPS) ≥ 70%.\n- 5. Adequate organ and marrow function."}

Exclusion criteria

  • {"criterion_text":"- 1. Prior systemic anticancer therapy for unresectable locally advanced or metastatic RCC including investigational agents.\n- 2. Uncontrolled, significant intercurrent or recent illness including, but not limited to serious cardiovascular disorders (including uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment), GI disorders associated with high risk for perforation or fistula formation, tumors invading GI tract, bowel obstruction, intra-abdominal abscess, clinically significant bleeding events, cavitating pulmonary lesions, or lesion invading major pulmonary blood vessels.\n- 3. Other clinically significant disorders such as: i. Autoimmune disease that has been symptomatic or required treatment within the past two years from the date of randomization. ii. Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. iii. Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known positive test for tuberculosis infection where there is clinical or radiographic evidence of active mycobacterial infection. iv. Known history of COVID-19 unless the subject has clinically recovered from the disease at least 30 days prior to randomization.\n- 4. Major surgery (eg, nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 4 weeks prior to randomization. Minor surgeries within 10 days prior to randomization. Subjects must have complete wound healing from major or minor surgery before randomization.\n- 5. Any other active malignancy at time of randomization or diagnosis of another malignancy within 3 years prior to randomization that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Duration of PFS (Progression-Free Survival), per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), by Blinded Independent Radiology Committee (BIRC)","definition_or_measurement_approach":"per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), by Blinded Independent Radiology Committee (BIRC)"}

Secondary endpoints

  • {"endpoint_text":"- Duration of OS (overall survival)","definition_or_measurement_approach":"Overall survival (OS) measured as duration of survival from randomization"}

Recruitment

Planned Sample Size
517
Recruitment Window Months
73
Consent Approach
Informed consent obtained from adult participants. Subject information and informed consent forms (Main ICF, Consent to Continue, Optional Samples ICF, Pregnant Partner ICF, Remote Visit Direct Drug Supply ICF) are provided; multiple country- and language-specific ICFs are available (document titles indicate English (EN), French (FR), Dutch/Deutsch (DU), Dutch/Netherlands (NL), Polish (PL), Italian (IT), Spanish (ES) versions). Consent is provided by the participant; partner-specific information is available for pregnant partners.

Geography

Total Number Of Sites
47
Total Number Of Participants
338

Belgium

Latest Decision Or Authorization Date
16-10-2024
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Institut Jules Bordet
Department Name
Oncology
Principal Investigator Name
Spyridon Sideris
Principal Investigator Email
spyridon.sideris@hubruxelles.be
Contact Person Name
Spyridon Sideris

Czechia

Latest Decision Or Authorization Date
17-10-2024
Number Of Sites
3
Number Of Participants
12

Sites

Site Name
Fakultni Nemocnice Hradec Kralove
Department Name
Klinika Onkologie a radioterapie
Principal Investigator Name
Jindřich Kopecký
Principal Investigator Email
jindrich.kopecky@fnhk.cz
Contact Person Name
Jindřich Kopecký
Contact Person Email
jindrich.kopecky@fnhk.cz
Site Name
Fakultni Thomayerova nemocnice
Department Name
Onkologická klinika 1. LF UK a TN
Principal Investigator Name
Tomáš Büchler
Principal Investigator Email
tomas.buchler@ftn.cz
Contact Person Name
Tomáš Büchler
Contact Person Email
tomas.buchler@ftn.cz
Site Name
Fakultni Nemocnice V Motole
Department Name
Onkologická klinika 2. LF UK
Principal Investigator Name
Kateřina Kopečková
Principal Investigator Email
katerina.kopeckova@fnmotol.cz
Contact Person Name
Kateřina Kopečková
Contact Person Email
katerina.kopeckova@fnmotol.cz

Finland

Latest Decision Or Authorization Date
15-10-2024
Number Of Sites
3
Number Of Participants
10

Sites

Site Name
HUS-Yhtymae
Department Name
Comprehensive Cancer Center
Principal Investigator Name
Jalkanen Katriina
Principal Investigator Email
katriina.jalkanen@hus.fi
Contact Person Name
Jalkanen Katriina
Contact Person Email
katriina.jalkanen@hus.fi
Site Name
Pirkanmaan hyvinvointialue
Department Name
Department of Oncology
Principal Investigator Name
Krista Kankaanranta
Principal Investigator Email
krista.kankaanranta@pirha.fi
Contact Person Name
Krista Kankaanranta
Contact Person Email
krista.kankaanranta@pirha.fi
Site Name
Turku University Hospital
Department Name
Department of Oncology
Principal Investigator Name
Kalle Mattila
Principal Investigator Email
kalle.mattila@varha.fi
Contact Person Name
Kalle Mattila
Contact Person Email
kalle.mattila@varha.fi

Germany

Latest Decision Or Authorization Date
15-10-2024
Number Of Sites
6
Number Of Participants
20

Sites

Site Name
Universitaetsklinikum Jena KöR
Department Name
Klinik und Poliklinik für Urologie
Principal Investigator Name
Marc-Oliver Grimm
Principal Investigator Email
marc-oliver.grimm@med.uni-jena.de
Contact Person Name
Marc-Oliver Grimm
Site Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Department Name
Department Urology and Pediatric Urology
Principal Investigator Name
Rene Mager
Principal Investigator Email
rene.mager@unimedizin-mainz.de
Contact Person Name
Rene Mager
Contact Person Email
rene.mager@unimedizin-mainz.de
Site Name
Universitaetsklinikum Muenster AöR
Department Name
Klinik für Urologie und Kinderurologie
Principal Investigator Name
Martin Boegemann
Principal Investigator Email
Martin.boegemann@ukmuenster.de
Contact Person Name
Martin Boegemann
Contact Person Email
Martin.boegemann@ukmuenster.de
Site Name
National Center For Tumor Diseases (NCT) Heidelberg
Department Name
-
Principal Investigator Name
Stefanie Zschäbitz
Principal Investigator Email
Stefanie.zschaebitz@med.uni-heidelberg.de
Contact Person Name
Stefanie Zschäbitz
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Department of Urology
Principal Investigator Name
Steffen Rausch
Principal Investigator Email
steffen.rausch@med.uni-tuebingen.de
Contact Person Name
Steffen Rausch
Site Name
Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
Department Name
Klinik und Poliklinik für Urologie
Principal Investigator Name
Angelika Borkowetz
Contact Person Name
Angelika Borkowetz

Italy

Latest Decision Or Authorization Date
21-10-2024
Number Of Sites
6
Number Of Participants
50

Sites

Site Name
Azienda Ospedaliera S Maria Di Terni
Department Name
S.C. Oncologia
Principal Investigator Name
Sergio Bracarda
Principal Investigator Email
sergio.bracarda@gmail.com
Contact Person Name
Sergio Bracarda
Contact Person Email
sergio.bracarda@gmail.com
Site Name
Istituto Oncologico Veneto
Department Name
UOC Oncologia 1
Principal Investigator Name
Umberto Basso
Principal Investigator Email
umberto.basso@iov.veneto.it
Contact Person Name
Umberto Basso
Contact Person Email
umberto.basso@iov.veneto.it
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
U.O. di Oncologia
Principal Investigator Name
Francesco Carrozza
Principal Investigator Email
francesco.carrozza@auslromagna.it
Contact Person Name
Francesco Carrozza
Site Name
Azienda Ospedaliero Universitaria Di Modena
Department Name
U.O. Oncologia
Principal Investigator Name
Roberto Sabbatini
Principal Investigator Email
roberto.sabbatini@unimore.it
Contact Person Name
Roberto Sabbatini
Contact Person Email
roberto.sabbatini@unimore.it
Site Name
Istituti Clinici Scientifici Maugeri S.p.A.
Department Name
U.O. Oncologia
Principal Investigator Name
Andrea Premoli
Principal Investigator Email
andrea.premoli@icsmaugeri.it
Contact Person Name
Andrea Premoli
Contact Person Email
andrea.premoli@icsmaugeri.it
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
S.C. Oncologia Medica
Principal Investigator Name
Ugo De Giorgi
Principal Investigator Email
ugo.degiorgi@irst.emr.it
Contact Person Name
Ugo De Giorgi
Contact Person Email
ugo.degiorgi@irst.emr.it

Spain

Latest Decision Or Authorization Date
14-10-2024
Number Of Sites
11
Number Of Participants
67

Sites

Site Name
Hospital Universitario Central De Asturias
Department Name
Oncology
Principal Investigator Name
Emilio Esteban
Principal Investigator Email
eestebang@seom.org
Contact Person Name
Emilio Esteban
Contact Person Email
eestebang@seom.org
Site Name
Hospital Clinico San Carlos
Department Name
Oncology
Principal Investigator Name
Javier Puente Vazquez
Principal Investigator Email
javierpuente.hcsc@gmail.com
Contact Person Name
Javier Puente Vazquez
Contact Person Email
javierpuente.hcsc@gmail.com
Site Name
Hospital Clinic De Barcelona
Department Name
Oncology
Principal Investigator Name
Begoña Mellado González
Principal Investigator Email
BMELLADO@CLINIC.CAT
Contact Person Name
Begoña Mellado González
Contact Person Email
BMELLADO@CLINIC.CAT
Site Name
Fundacion Instituto Valenciano De Oncologia
Department Name
Oncology
Principal Investigator Name
Maria Jose Juan Fita
Principal Investigator Email
mjjuan@fivo.org
Contact Person Name
Maria Jose Juan Fita
Contact Person Email
mjjuan@fivo.org
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncology
Principal Investigator Name
Cristina Suárez Rodríguez
Principal Investigator Email
csuarez@vhio.net
Contact Person Name
Cristina Suárez Rodríguez
Contact Person Email
csuarez@vhio.net
Site Name
Hospital Universitario Hm Sanchinarro
Department Name
Oncology
Principal Investigator Name
Jesus Garcia Donas
Principal Investigator Email
jgarciadonas@gmail.com
Contact Person Name
Jesus Garcia Donas
Contact Person Email
jgarciadonas@gmail.com
Site Name
Clinica Universidad De Navarra
Department Name
Oncology
Principal Investigator Name
Jose Luis Perez Gracia
Principal Investigator Email
jlgracia@unav.es
Contact Person Name
Jose Luis Perez Gracia
Contact Person Email
jlgracia@unav.es
Site Name
Hospital Universitario Reina Sofia
Department Name
Oncology
Principal Investigator Name
Maria Jose Mendez Vidal
Principal Investigator Email
MJOSEMV@YAHOO.ES
Contact Person Name
Maria Jose Mendez Vidal
Contact Person Email
MJOSEMV@YAHOO.ES
Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncology
Principal Investigator Name
Daniel Ernesto Castellano
Principal Investigator Email
cdanicas@hotmail.com
Contact Person Name
Daniel Ernesto Castellano
Contact Person Email
cdanicas@hotmail.com
Site Name
Complexo Hospitalario Universitario De Santiago
Department Name
Oncology
Principal Investigator Name
Urbano Anido Herranz
Principal Investigator Email
urbano.anido.herranz@sergas.es
Contact Person Name
Urbano Anido Herranz
Contact Person Email
urbano.anido.herranz@sergas.es
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Oncology
Principal Investigator Name
Jose Angel Arranz Arija
Principal Investigator Email
jarranza.oncomed@gmail.com
Contact Person Name
Jose Angel Arranz Arija
Contact Person Email
jarranza.oncomed@gmail.com

Netherlands

Latest Decision Or Authorization Date
27-10-2024
Number Of Sites
2
Number Of Participants
7

Sites

Site Name
Amsterdam UMC Stichting
Department Name
Oncology
Principal Investigator Name
Astridt van der Veldt
Principal Investigator Email
a.vanderveldt@erasmusmc.nl
Contact Person Name
Astridt van der Veldt
Contact Person Email
a.vanderveldt@erasmusmc.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Oncology
Principal Investigator Name
Adriaan Bins
Principal Investigator Email
a.d.bins@amsterdamumc.nl
Contact Person Name
Adriaan Bins
Contact Person Email
a.d.bins@amsterdamumc.nl

Poland

Latest Decision Or Authorization Date
07-11-2024
Number Of Sites
5
Number Of Participants
101

Sites

Site Name
Med Polonia Sp. z o.o.
Principal Investigator Name
Rodryg Ramlau
Principal Investigator Email
badania.kliniczne@medpolonia.pl
Contact Person Name
Rodryg Ramlau
Site Name
Wojewodzki Szpital Specjalistyczny W Bialej Podlaskiej
Department Name
Oddział Onkologii Klinicznej
Principal Investigator Name
Piotr Centkowski
Principal Investigator Email
pcentek@wp.pl
Contact Person Name
Piotr Centkowski
Contact Person Email
pcentek@wp.pl
Site Name
Copernicus Podmiot Leczniczy Sp. z o.o.
Department Name
Wojewódzkie Centrum Onkologii
Principal Investigator Name
Joanna Wójcik-Tomaszewska
Principal Investigator Email
jwojcik@wco.gda.pl
Contact Person Name
Joanna Wójcik-Tomaszewska
Contact Person Email
jwojcik@wco.gda.pl
Site Name
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
Department Name
Centrum Onkologii
Principal Investigator Name
Bogdan Żurawski
Principal Investigator Email
bzur1@wp.pl
Contact Person Name
Bogdan Żurawski
Contact Person Email
bzur1@wp.pl
Site Name
Europejskie Centrum Zdrowia Otwock Sp. z o.o.
Department Name
Szpital im. F. Chopina Oddział Onkologii Klinicznej
Principal Investigator Name
Cezary Szczylik
Principal Investigator Email
cezary.szczylik@ecz-otwock.pl
Contact Person Name
Cezary Szczylik
Contact Person Email
cezary.szczylik@ecz-otwock.pl

France

Latest Decision Or Authorization Date
23-12-2024
Number Of Sites
10
Number Of Participants
69

Sites

Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Oncology
Principal Investigator Name
Marine Gross-Goupil
Principal Investigator Email
marine.gross-goupil@chu-bordeaux.fr
Contact Person Name
Marine Gross-Goupil
Site Name
Institut De Cancerologie De Lorraine
Department Name
Oncology
Principal Investigator Name
Lionnel Geoffrois
Principal Investigator Email
l.geoffrois@nancy.unicancer.fr
Contact Person Name
Lionnel Geoffrois
Contact Person Email
l.geoffrois@nancy.unicancer.fr
Site Name
Centre Leon Berard
Department Name
Oncology
Principal Investigator Name
Sylvie Negrier
Principal Investigator Email
sylvie.negrier@lyon.unicancer.fr
Contact Person Name
Sylvie Negrier
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Oncology
Principal Investigator Name
de Topart
Principal Investigator Email
d-topart@chu-montpellier.fr
Contact Person Name
de Topart
Contact Person Email
d-topart@chu-montpellier.fr
Site Name
Centre Antoine Lacassagne
Department Name
Oncology
Principal Investigator Name
Delphine Brochiellini
Principal Investigator Email
delphine.brochiellini@nice.unicancer.fr
Contact Person Name
Delphine Brochiellini
Site Name
Institut Godinot
Department Name
Oncology
Principal Investigator Name
Jean-Christophe Eymard
Principal Investigator Email
jeanchristophe.eymard@reims.unicancer.fr
Contact Person Name
Jean-Christophe Eymard
Site Name
Oncopole Claudius Regaud
Department Name
Oncology
Principal Investigator Name
Damien Pouessel
Principal Investigator Email
pouessel.damien@iuct-oncopole.fr
Contact Person Name
Damien Pouessel
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Oncology
Principal Investigator Name
Philippe Barthelemy
Principal Investigator Email
p.barthelemy@icans.eu
Contact Person Name
Philippe Barthelemy
Contact Person Email
p.barthelemy@icans.eu
Site Name
Institut Gustave Roussy
Department Name
Oncology
Principal Investigator Name
Laurence Albiges
Principal Investigator Email
laurence.albiges@gustaveroussy.fr
Contact Person Name
Laurence Albiges
Site Name
Clinique Victor Hugo
Department Name
Oncology
Principal Investigator Name
Eric Voog
Principal Investigator Email
essaisvoog@ilcgroupe.fr
Contact Person Name
Eric Voog
Contact Person Email
essaisvoog@ilcgroupe.fr

Sponsor

Primary sponsor

Full Name
Exelixis Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Medpace Finland Oy
Responsibilities
codes: 1,2,5
Name
Medqia LLC
Responsibilities
Central imaging review
Name
Icon Laboratory Services Inc.
Responsibilities
Local Lab Report Review; code 8
Name
Drugdev Inc.
Responsibilities
Site Payments
Name
Labcorp Central Laboratory Services LP
Responsibilities
code 4

Third parties

  • {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"codes: 1,2,5","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medqia LLC","duties_or_roles":"Central imaging review","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Local Lab Report Review; code 8","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Drugdev Inc.","duties_or_roles":"Site Payments","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
CABOMETYX 20 mg film-coated tablets
Active Substance
cabozantinib
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
oral
Authorisation Status
Authorised (marketing authorisation EU/1/16/1136/002)
Starting Dose
20 mg (film-coated tablet)
Maximum Dose
40 mg (maxDailyDoseAmount)
Investigational Product Name
OPDIVO 10 mg/mL concentrate for solution for infusion.
Active Substance
nivolumab
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS USE
Route
intravenous
Authorisation Status
Authorised (marketing authorisation EU/1/15/1014/002)
Maximum Dose
3 mg/kg (maxDailyDoseAmount)
Investigational Product Name
YERVOY 5 mg/ml concentrate for solution for infusion
Active Substance
ipilimumab
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS USE
Route
intravenous
Authorisation Status
Authorised (marketing authorisation EU/1/11/698/002)
Maximum Dose
1 mg/kg (maxDailyDoseAmount)
Investigational Product Name
Placebo Tablets matching Cabozantinib (XL184) 20mg tablets.
Modality
Other
Starting Dose
matching Cabozantinib 20 mg tablet
Combination Treatment
Yes

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