Clinical trial NCT04338269: A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment
Official title: A Phase III, Multicenter, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Atezolizumab Given in Combination With Cabozantinib Versus Cabozantinib Alone in Patients With Inoperable, Locally Advanced, or Metastatic Renal Cell Carcinoma Who Experienced Radiographic Tumor Progression During or After Immune Checkpoint Inhibitor Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Renal Cell
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Exelixis
name: Chugai Pharmaceutical
First posted: 2020-04-08
Enrollment: 522
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase III, multicenter, randomized, open-label study designed to evaluate the efficacy and safety of atezolizumab given in combination with cabozantinib versus cabozantinib alone in participants with inoperable, locally advanced, or metastatic renal cell carcinoma (RCC) who experienced radiographic tumor progression during or after Immune Checkpoint Inhibitor (ICI) treatment in the metastatic setting.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed locally advanced or metastatic clear cell or non-clear cell (papillary, chromophobe, and unclassified only) RCC. RCC with sarcomatoid features is allowed. Patients with the chromophobe subtype of non-clear cell RCC must have sarcomatoid differentiation.
* Radiographic disease progression to prior ICI therapy for RCC. Patients who experienced radiographic tumor progression during or within 6 months after the last dose of adjuvant ICI are also eligible. ICI is defined by anti-PD-L1 or anti-PD1 antibody including atezolizumab, avelumab, pembrolizumab, durvalumab, or nivolumab. Only patients for whom the immediate preceding line of therapy was an ICI are allowed.
* Measurable disease per RECIST v1.1
* Evaluable IMDC risk score
* Archival tumor specimen, and pretreatment tumor tissue from fresh biopsy at screening, if clinically feasible. Both archival and fresh samples are preferred.
* KPS score of \>=70
* Recovery to baseline or Grade \</= 1 NCI CTCAE v5.0 from toxicities related to any prior treatments, unless adverse events are clinically nonsignificant and/or stable in the opinion of the investigator. Grade 2 alopecia is allowed for study participation
* Adequate hematologic and end-organ function
* Negative HIV test at screening
* Negative hepatitis B testing at screening
* Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

Exclusion Criteria:

* Treatment with anti-cancer therapy within 14 days prior to initiation of study treatment
* Patients received cabozantinib at any time prior to screening
* Patients who received more than one ICI treatment in the locally advanced or metastatic setting
* Patients who received more than two prior lines of therapy in the locally advanced or metastatic setting
* Patients who have received a mammalian target of rapamycin (mTOR) inhibitor in any setting
* Symptomatic, untreated, or actively progressing CNS metastases
* History of leptomeningeal disease
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
* Uncontrolled or symptomatic hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
* History of malignancy other than renal carcinoma within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
* Radiotherapy for RCC within 14 days prior to Day 1 of Cycle 1
* Active tuberculosis
* Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
* Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after final dose of atezolizumab and 4 months after final dose of cabozantinib
* Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion of the investigator, could impact patient safety
* Pharmacologically uncompensated, symptomatic hypothyroidism
* Uncontrolled hypertension defined as sustained blood pressure \>150 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment (all countries except France); sustained BP \> 140 mmHg systolic or \> 90 mmHg diastolic despite optimal antihypertensive treatment (France only)
* Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, unstable arrhythmia, or unstable angina) within 3 months prior to initiation of study treatment
* Significant vascular disease (e.g., aortic aneurysm or arterial dissection requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 of Cycle 1
* History of congenital QT syndrome
* History or presence of an abnormal ECG that is clinically significant in the investigator's opinion
* Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g. clopidogrel)

Primary outcomes:
measure: Progression Free Survival (PFS) as Assessed by an Independent Review Facility (IRF) (IRF-PFS) According to RECIST v1.1
timeFrame: From randomization to the first occurrence of disease progression according to RECIST v1.1 (up to 2 years 5 months).
measure: Overall Survival (OS)
timeFrame: From randomization to death due to any cause (up to 2 years 5 months).
Secondary outcomes:
measure: Progression Free Survival (PFS) as Assessed by Investigators (INV-PFS), According to RECIST v1.1
timeFrame: From randomization to the first occurrence of disease progression according to RECIST v1.1 or death from any cause (whichever occurs first) (up to 2 years 5 months).
measure: Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1
timeFrame: From randomization to the first occurrence of disease progression according to RECIST v1.1 or death from any cause (whichever occurs first) (up to 2 years 5 months).
measure: Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1
timeFrame: From randomization to the first occurrence of disease progression according to RECIST v1.1 or death from any cause (whichever occurs first) (up to 2 years 5 months).
measure: Investigator-assessed Duration of Response (DOR) (INV-DOR) According to RECIST v1.1
timeFrame: From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 2 years 5 months)
measure: Independent Review Facility (IRF)-Assessed Duration of Response (DOR) (IRF-DOR) According to RECIST v1.1
timeFrame: From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 2 years 5 months)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: La Jolla
country: United States
facility: UC San Diego Health System
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Littleton
country: United States
facility: Rocky Mountain Cancer Center - Denver
state: Colorado
city: Pensacola
country: United States
facility: Woodlands Medical Specialists, P.A.
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley
state: Nevada
city: Middletown
country: United States
facility: Memorial Sloan Kettering - Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology,P.C.-Albany
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Austin
country: United States
facility: Texas Oncology - Central South
state: Texas
city: Salt Lake City
country: United States
facility: University Of Utah
state: Utah
city: Gainesville
country: United States
facility: Virginia Cancer Specialists - Gainsville
state: Virginia
city: Buenos Aires
country: Argentina
facility: Fundación CENIT para la Investigación en Neurociencias
city: Buenos Aires
country: Argentina
facility: Inst. Alexander Fleming
city: Ciudad Autonoma Bs As
country: Argentina
facility: Hospital Britanico
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Centro Medico Austral OMI
city: Orange
country: Australia
facility: Orange Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Icon Cancer Foundation
state: Queensland
city: Bendigo
country: Australia
facility: Bendigo Cancer Centre
state: Victoria
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Besançon Cedex
country: France
facility: CHU Besançon - Hôpital Jean Minjoz
city: Bordeaux
country: France
facility: CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre
city: Caen
country: France
facility: Centre Francois Baclesse
city: Lille
country: France
facility: Centre Oscar Lambret
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Strasbourg
country: France
facility: ICANS
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Chemnitz
country: Germany
facility: Zeisigwaldkliniken Bethanien
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Halle (Saale)
country: Germany
facility: Krankenhaus Martha-Maria Halle-Dölau, Klinik für Urologie
city: Hamburg
country: Germany
facility: Uniklinik-Eppendorf
city: Hannover
country: Germany
facility: Med. Hochschule Hannover, Hämatologie, Hämostaseologie, Onkologie u. Stammzelltransplantation
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Athens
country: Greece
facility: Alexandras General Hospital of Athens
city: Athens
country: Greece
facility: Attikon University General Hospital
city: Athens
country: Greece
facility: Athens Medical Center
city: Larissa
country: Greece
facility: University Hospital of Larissa
city: Thessaloniki
country: Greece
facility: Diavalkaniko Hospital
city: Napoli
country: Italy
facility: Istituto Tumori Napoli
state: Campania
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria S.Orsola-Malpighi
state: Emilia-Romagna
city: Meldola
country: Italy
facility: IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
state: Emilia-Romagna
city: Roma
country: Italy
facility: Policlinico Universitario "Agostino Gemelli"
state: Lazio
city: Brescia
country: Italy
facility: Asst Degli Spedali Civili Di Brescia
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int)
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri
state: Lombardia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Lombardia
city: Macerata
country: Italy
facility: Ospedale Di Macerata
state: Marche
city: Candiolo (TO)
country: Italy
facility: Fondazione del Piemonte per l?Oncologia (IRCCS)
state: Piemonte
city: Bari
country: Italy
facility: A.O. Universitaria Ospedale Consorziale Policlinico Di Bari
state: Puglia
city: Terni
country: Italy
facility: Azienda Ospedaliera S. Maria - Terni
state: Umbria
city: Verona
country: Italy
facility: A.O.U di Verona Policlinico G.B. Rossi
state: Veneto
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Ibaraki
country: Japan
facility: University of Tsukuba Hospital
city: Kanagawa
country: Japan
facility: Yokohama City University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Tokushima
country: Japan
facility: Tokushima University Hospital
city: Tokyo
country: Japan
facility: Keio University Hospital
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: CHA Bundang Medical Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Gyeongsangnam-do
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: ?ód?
country: Poland
facility: Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka ?ukaszczyka
city: Bytom
country: Poland
facility: SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii
city: Pozna?
country: Poland
facility: Szpital Kliniczny im. Heliodora ?wi?cickiego UM w Poznaniu
city: Warszawa
country: Poland
facility: Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny
city: Wroc?aw
country: Poland
facility: Dolno?l?skie Centrum Onkologii, Pulmonologii i Hematologii
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Oncology Hospital
state: Jaroslavl
city: Kuzmolovo
country: Russian Federation
facility: St-Petersburg Regional Oncology Dispensary
state: Leningrad
city: Sankt-peterburg
country: Russian Federation
facility: AV Medical Ltd.
state: Leningrad
city: Innovatsionnogo Tsentra Skolkovo
country: Russian Federation
facility: Branch of the company "Hadassah Medical LTD"
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
state: Moskovskaja Oblast
city: Moskva
country: Russian Federation
facility: SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"
state: Moskovskaja Oblast
city: St. Petersburg
country: Russian Federation
facility: Private Healthcare Institution Clinical Hospital RZhD Medicine
state: Sankt Petersburg
city: Novosibirsk
country: Russian Federation
facility: Medical Center Avicenna
city: Oviedo
country: Spain
facility: Hospital Univ. Central de Asturias
state: Asturias
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
state: Cordoba
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Islas Baleares
city: Vigo
country: Spain
facility: Hospital Alvaro Cunqueiro
state: Pontevedra
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Caceres
country: Spain
facility: Hospital San Pedro De Alcantara
city: Lugo
country: Spain
facility: Hospital Lucus Augusti
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de Arrixaca
city: Navarra
country: Spain
facility: Hospital de Navarra
city: Valencia
country: Spain
facility: Hospital Universitario la Fe
city: Blackburn
country: United Kingdom
facility: Royal Blackburn Hospital
city: London
country: United Kingdom
facility: Barts & London School of Med
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Yang Y, Psutka SP, Parikh AB, Li M, Collier K, Miah A, Mori SV, Hinkley M, Tykodi SS, Hall E, Thompson JA, Yin M. Combining immune checkpoint inhibition plus tyrosine kinase inhibition as first and subsequent treatments for metastatic renal cell carcinoma. Cancer Med. 2022 Aug;11(16):3106-3114. doi: 10.1002/cam4.4679. Epub 2022 Mar 18.