A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment

NCT ID: NCT04338269

Last Updated: 2025-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 522 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-28
• Study Completion Date: 2025-03-24

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.

Conditions

Carcinoma, Renal Cell

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atezo+Cabo

Participants will receive atezolizumab every 3 weeks on Day 1 of each 21-day cycle (1 cycle=21 days) plus oral tablets of cabozantinib every day.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 mg will be administered at a fixed dose on Day 1 of each 21-day cycle by IV infusion every 3 weeks.

Cabozantinib

Intervention Type: DRUG

Cabozantinib 60 mg (three 20-mg tablets) administered orally once daily.

Cabozantinib

Participants will receive cabozantinib every day.

Group Type: ACTIVE_COMPARATOR

Cabozantinib

Intervention Type: DRUG

Cabozantinib 60 mg (three 20-mg tablets) administered orally once daily.

Interventions

Atezolizumab

Atezolizumab 1200 mg will be administered at a fixed dose on Day 1 of each 21-day cycle by IV infusion every 3 weeks.

Intervention Type: DRUG

Cabozantinib

Cabozantinib 60 mg (three 20-mg tablets) administered orally once daily.

Intervention Type: DRUG

Other Intervention Names

Tecentriq; Cabometyx

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Exelixis

INDUSTRY

Sponsor Role: collaborator

Chugai Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

University of Arizona

Tucson, Arizona, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

UC San Diego Health System

La Jolla, California, United States

UCLA

Los Angeles, California, United States

University of Colorado

Aurora, Colorado, United States

Rocky Mountain Cancer Center - Denver

Littleton, Colorado, United States

Woodlands Medical Specialists, P.A.

Pensacola, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Minnesota Oncology Hematology

Minneapolis, Minnesota, United States

Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley

Las Vegas, Nevada, United States

Memorial Sloan Kettering - Monmouth

Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

New York Oncology Hematology,P.C.-Albany

Albany, New York, United States

Mount Sinai Medical Center

New York, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Texas Oncology - Central South

Austin, Texas, United States

University Of Utah

Salt Lake City, Utah, United States

Virginia Cancer Specialists - Gainsville

Gainesville, Virginia, United States

Fundación CENIT para la Investigación en Neurociencias

Buenos Aires, , Argentina

Inst. Alexander Fleming

Buenos Aires, , Argentina

Hospital Britanico

Ciudad Autonoma Bs As, , Argentina

Centro Medico Austral OMI

Ciudad Autonoma Buenos Aires, , Argentina

Orange Hospital

Orange, New South Wales, Australia

Icon Cancer Foundation

South Brisbane, Queensland, Australia

Bendigo Cancer Centre

Bendigo, Victoria, Australia

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Herlev Hospital

Herlev, , Denmark

CHU Besançon - Hôpital Jean Minjoz

Besançon, , France

CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre

Bordeaux, , France

Centre Francois Baclesse

Caen, , France

Centre Oscar Lambret

Lille, , France

Hopital Europeen Georges Pompidou

Paris, , France

ICANS

Strasbourg, , France

Institut Gustave Roussy

Villejuif, , France

Zeisigwaldkliniken Bethanien

Chemnitz, , Germany

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt, , Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Krankenhaus Martha-Maria Halle-Dölau, Klinik für Urologie

Halle, , Germany

Uniklinik-Eppendorf

Hamburg, , Germany

Med. Hochschule Hannover, Hämatologie, Hämostaseologie, Onkologie u. Stammzelltransplantation

Hanover, , Germany

Klinikum rechts der Isar der TU München

München, , Germany

Universitaetsklinikum Muenster

Münster, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Alexandras General Hospital of Athens

Athens, , Greece

Attikon University General Hospital

Athens, , Greece

Athens Medical Center

Athens, , Greece

University Hospital of Larissa

Larissa, , Greece

Diavalkaniko Hospital

Thessaloniki, , Greece

A.O. Universitaria Ospedale Consorziale Policlinico Di Bari

Bari, Apulia, Italy

Istituto Tumori Napoli

Napoli, Campania, Italy

Azienda Ospedaliero-Universitaria S.Orsola-Malpighi

Bologna, Emilia-Romagna, Italy

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola

Meldola, Emilia-Romagna, Italy

Policlinico Universitario "Agostino Gemelli"

Rome, Lazio, Italy

Asst Degli Spedali Civili Di Brescia

Brescia, Lombardy, Italy

Irccs Istituto Nazionale Dei Tumori (Int)

Milan, Lombardy, Italy

Fondazione Salvatore Maugeri

Pavia, Lombardy, Italy

Istituto Clinico Humanitas

Rozzano, Lombardy, Italy

Fondazione del Piemonte per l?Oncologia (IRCCS)

Candiolo (TO), Piedmont, Italy

Ospedale Di Macerata

Macerata, The Marches, Italy

Azienda Ospedaliera S. Maria - Terni

Terni, Umbria, Italy

A.O.U di Verona Policlinico G.B. Rossi

Verona, Veneto, Italy

Hokkaido University Hospital

Hokkaido, , Japan

University of Tsukuba Hospital

Ibaraki, , Japan

Yokohama City University Hospital

Kanagawa, , Japan

Okayama University Hospital

Okayama, , Japan

Osaka Metropolitan University Hospital

Osaka, , Japan

Tokushima University Hospital

Tokushima, , Japan

Keio University Hospital

Tokyo, , Japan

Tokyo Women's Medical University Hospital

Tokyo, , Japan

Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna

?ód?, , Poland

Centrum Onkologii im. Prof. Franciszka ?ukaszczyka

Bydgoszcz, , Poland

SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4

Bytom, , Poland

Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii

Otwock, , Poland

Szpital Kliniczny im. Heliodora ?wi?cickiego UM w Poznaniu

Późna, , Poland

Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.

Warsaw, , Poland

Wojskowy Instytut Medyczny

Warsaw, , Poland

Dolno?l?skie Centrum Onkologii, Pulmonologii i Hematologii

Wroc?aw, , Poland

St-Petersburg Regional Oncology Dispensary

Kuzmolovo, Leningrad, Russia

Branch of the company "Hadassah Medical LTD"

Innovatsionnogo Tsentra Skolkovo, Moscow Oblast, Russia

FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"

Moscow, Moscow Oblast, Russia

SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"

Moskva, Moscow Oblast, Russia

Private Healthcare Institution Clinical Hospital RZhD Medicine

Saint Petersburg, Sankt-Peterburg, Russia

AV Medical Ltd.

Saint Petersburg, Sankt-Peterburg, Russia

Regional Clinical Oncology Hospital

Yaroslavl, Yaroslavl Oblast, Russia

Medical Center Avicenna

Novosibirsk, , Russia

Chungnam National University Hospital

Daejeon, , South Korea

CHA Bundang Medical Center

Gyeonggi-do, , South Korea

Seoul National University Bundang Hospital

Gyeonggi-do, , South Korea

Pusan National University Yangsan Hospital

Gyeongsangnam-do, , South Korea

Chonnam National University Hwasun Hospital

Jeollanam-do, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, Spain

Corporacio Sanitaria Parc Tauli

Sabadell, Barcelona, Spain

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, Spain

Hospital Universitario Reina Sofia

Córdoba, Cordoba, Spain

Hospital de Navarra

Navarra, Navarre, Spain

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, Spain

Hospital Univ. Central de Asturias

Oviedo, Principality of Asturias, Spain

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario de Burgos

Burgos, , Spain

Hospital San Pedro De Alcantara

Cáceres, , Spain

Hospital Lucus Augusti

Lugo, , Spain

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Hospital Ramon y Cajal

Madrid, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Clinico Universitario Virgen de la Victoria

Málaga, , Spain

Hospital Universitario Virgen de Arrixaca

Murcia, , Spain

Hospital Universitario la Fe

Valencia, , Spain

Royal Blackburn Hospital

Blackburn, , United Kingdom

Barts & London School of Med

London, , United Kingdom

Royal Marsden Hospital

London, , United Kingdom

Christie Hospital Nhs Trust

Manchester, , United Kingdom

Countries

United States; Argentina; Australia; Canada; Denmark; France; Germany; Greece; Italy; Japan; Poland; Russia; South Korea; Spain; United Kingdom

References

Pal SK, Albiges L, Tomczak P, Suarez C, Voss MH, de Velasco G, Chahoud J, Mochalova A, Procopio G, Mahammedi H, Zengerling F, Kim C, Osawa T, Angel M, Gupta S, Khan O, Bergthold G, Liu B, Kalaitzidou M, Huseni M, Scheffold C, Powles T, Choueiri TK. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2023 Jul 15;402(10397):185-195. doi: 10.1016/S0140-6736(23)00922-4. Epub 2023 Jun 5.

Reference Type: DERIVED

PMID: 37290461 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35304832 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

WO41994

Identifier Type: -

Identifier Source: org_study_id