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

Carcinoma, Renal Cell Clinical Trial

— CONTACT-03  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04338269
• Other study ID #: WO41994
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 28, 2020
• Est. completion date: June 30, 2024

Study information

• Verified date: March 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 522
• Est. completion date: June 30, 2024
• Est. primary completion date: January 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell

Intervention

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

Locations

Country	Name	City	State
Argentina	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires
Argentina	Inst. Alexander Fleming; Oncologia	Buenos Aires
Argentina	Hospital Britanico	Ciudad Autonoma Bs As
Argentina	Centro Medico Austral OMI	Ciudad Autonoma Buenos Aires
Australia	Bendigo Cancer Centre	Bendigo	Victoria
Australia	Macquarie University Hospital	Macquarie Park	New South Wales
Australia	Orange Hospital	Orange	New South Wales
Australia	Icon Cancer Foundation	South Brisbane	Queensland
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Denmark	Herlev Hospital; Afdeling for Kræftbehandling	Herlev
France	CHU Besançon - Hôpital Jean Minjoz	Besançon Cedex
France	CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre	Bordeaux
France	Centre Francois Baclesse; Oncologie	Caen
France	Centre Jean Perrin; Oncologie	Clermont Ferrand
France	Centre Oscar Lambret; Chir Cancerologie General	Lille
France	Centre Leon Berard; Departement Oncologie Medicale	Lyon
France	Centre Antoine Lacassagne	Nice
France	Institut de cancerologie du Gard	Nimes
France	Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale	Paris
France	ICANS	Strasbourg
France	Institut Gustave Roussy; Oncologie Medicale	Villejuif
Germany	Zeisigwaldkliniken Bethanien	Chemnitz
Germany	Klinikum der Johann Wolfgang Goethe-Universitaet; Urologie und Kinderurologie	Frankfurt
Germany	Universitaetsklinikum Freiburg; Urology	Freiburg
Germany	Krankenhaus Martha-Maria Halle-Dölau, Klinik für Urologie	Halle (Saale)
Germany	Uniklinik-Eppendorf; Klinik U Poliklinik F Urologie	Hamburg
Germany	Med. Hochschule Hannover, Hämatologie, Hämostaseologie, Onkologie u. Stammzelltransplantation	Hannover
Germany	Universitaetsklinikum Muenster; Urology	Muenster
Germany	Klinikum rechts der Isar der TU München; Urologische Klinik und Poliklinik	München
Germany	Universitätsklinikum Tübingen; Klinik für Urologie	Tübingen
Germany	Universitätsklinikum Ulm; Klinik für Urologie	Ulm
Greece	Alexandras General Hospital of Athens; Oncology Department	Athens
Greece	Athens Medical Center; Dept. of Oncology	Athens
Greece	Attikon University General Hospital	Chaidari
Greece	University Hospital of Larissa;Department of Medical Oncology	Larissa
Greece	Diavalkaniko Hospital	Thessaloniki
Italy	A.O. Universitaria Ospedale Consorziale Policlinico Di Bari; U.O. Oncologia Medica Universitaria	Bari	Puglia
Italy	Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica	Bologna	Emilia-Romagna
Italy	ASST DEGLI SPEDALI CIVILI DI BRESCIA; Oncologia Medica	Brescia	Lombardia
Italy	Fondazione del Piemonte per l?Oncologia (IRCCS); Day Hospital Oncologico Multidisciplinare	Candiolo (TO)	Piemonte
Italy	Ospedale Di Macerata; Oncologia	Macerata	Marche
Italy	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2	Milano	Lombardia
Italy	Istituto Tumori Napoli;Unità Operativa Oncologia Medica Uro-Ginecologica	Napoli	Campania
Italy	Fondazione Salvatore Maugeri; Divisione Di Oncologia Medica	Pavia	Lombardia
Italy	Policlinico Universitario "Agostino Gemelli"; U.O.C. Oncologia Medica	Roma	Lazio
Italy	Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia	Rozzano	Lombardia
Italy	Azienda Ospedaliera S. Maria - Terni; Oncologia	Terni	Umbria
Italy	A.O.U di Verona Policlinico G.B. Rossi; Centro Ricerche Cliniche	Verona	Veneto
Japan	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
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	CHA Bundang Medical Center	Gyeonggi-do
Korea, Republic of	Pusan National University Yangsan Hospital	Gyeongsangnam-do
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Poland	Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna	?ód?
Poland	Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny	Brzozów
Poland	Centrum Onkologii im. Prof. Franciszka ?ukaszczyka; Ambulatorium Chemioterapii	Bydgoszcz
Poland	SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4; Oddzial Onkologii Klinicznej	Bytom
Poland	Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii	Otwock
Poland	Szpital Kliniczny im. Heliodora ?wi?cickiego UM w Poznaniu; Oddzia? Chemioterapii	Pozna?
Poland	Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.	Warszawa
Poland	Wojskowy Instytut Medyczny; Klinika Onkologii	Warszawa
Poland	Dolno?l?skie Centrum Onkologii, Pulmonologii i Hematologii	Wroc?aw
Russian Federation	Branch of the company "Hadassah Medical LTD"	Innovatsionnogo Tsentra Skolkovo	Moskovskaja Oblast
Russian Federation	St-Petersburg Regional Oncology Dispensary; Oncology	Kuzmolovo	Leningrad
Russian Federation	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"	Moscow	Moskovskaja Oblast
Russian Federation	MEDSI Clinical Hospital on Pyatnitsky Highway; Department of antitumor drug therapy	Moscow	Moskovskaja Oblast
Russian Federation	National Medical Research Center for Surgery named after A.V. Vishnevsky	Moskva	Moskovskaja Oblast
Russian Federation	SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"	Moskva	Moskovskaja Oblast
Russian Federation	Medical Center Avicenna; Urology	Novosibirsk
Russian Federation	AV Medical Ltd.	Sait-Petersburg Sankt Petersburg	Sankt Petersburg
Russian Federation	Private Healthcare Institution Clinical Hospital RZhD Medicine	St. Petersburg	Sankt Petersburg
Russian Federation	Regional Clinical Oncology Hospital	Yaroslavl	Jaroslavl
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Hospital Universitario de Burgos; Oncología	Burgos
Spain	Hospital San Pedro De Alcantara; Servicio de Oncologia	Caceres
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Hospital Lucus Augusti; Servicio de Oncologia	Lugo
Spain	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia	Murcia
Spain	Hospital de Navarra; Servicio de Oncologia	Navarra
Spain	Hospital Univ. Central de Asturias; Servicio de Oncologia	Oviedo	Asturias
Spain	Hospital Universitario Son Espases; Servicio de Oncologia	Palma De Mallorca	Islas Baleares
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Oncologia	Santander	Cantabria
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Hospital Universitario la Fe; Servicio de Oncologia	Valencia
Spain	Hospital Alvaro Cunqueiro; Servicio de Oncologia	Vigo	Pontevedra
United Kingdom	Royal Blackburn Hospital	Blackburn
United Kingdom	Leicester Royal Infirmary; Dept. of Medical Oncology	Leicester
United Kingdom	Barts & London School of Med; Medical Oncology	London
United Kingdom	Royal Marsden Hospital; Dept of Med-Onc	London
United Kingdom	Christie Hospital Nhs Trust; Medical Oncology	Manchester
United Kingdom	Royal Marsden Hospital (Sutton)	Sutton
United States	New York Oncology Hematology,P.C.-Albany	Albany	New York
United States	University of Colorado	Aurora	Colorado
United States	Texas Onc-Central Austin CA Ct	Austin	Texas
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Skip Viragh Outpatient Cancer Building	Baltimore	Maryland
United States	Beth Israel Deaconess Med Ctr	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	MGH	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Cleveland Clinic	Cleveland	Ohio
United States	Memorial Sloan Kettering Cancer Center - Commack	Commack	New York
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Virginia Cancer Specialists - Gainsville	Gainesville	Virginia
United States	MSKCC @ West Harrison	Harrison	New York
United States	UC San Diego Health System	La Jolla	California
United States	Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley	Las Vegas	Nevada
United States	Rocky Mountain Cancer Center - Denver	Littleton	Colorado
United States	UCLA	Los Angeles	California
United States	Memorial Sloan Kettering - Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	Woodlands Medical Specialists, P.A.	Pensacola	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Minnesota Oncology Hematology	Saint Paul	Minnesota
United States	University Of Utah	Salt Lake City	Utah
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Moffitt Cancer Center	Tampa	Florida
United States	University of Arizona	Tucson	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Chugai, Exelixis

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Denmark,  France,  Germany,  Greece,  Italy,  Japan,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) as Assessed by an Independent Review Facility (IRF) (IRF-PFS) According to RECIST v1.1	Progression Free Survival (PFS) is defined as the time from randomization to disease progression, as determined by the Independent Review Facility (IRF) per RECIST v1.1, or death from any cause, whichever occurs first. Data for patients who have not experienced disease progression or death were censored at the last tumor assessment date. Data for patients with no postbaseline tumor assessments were censored at the randomization date.	From randomization to the first occurrence of disease progression according to RECIST v1.1 (up to 2 years 5 months).
Primary	Overall Survival (OS)	From randomization to death due to any cause. Data for patients who are not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Patients who do not have post-baseline information were censored at the date of randomization.	From randomization to death due to any cause (up to 2 years 5 months).
Secondary	Progression Free Survival (PFS) as Assessed by Investigators (INV-PFS), According to RECIST v1.1	Progression Free Survival (PFS) is defined as the time from randomization to disease progression, as determined by the Investigators per RECIST v1.1, or death from any cause, whichever occurs first. Data for patients who have not experienced disease progression or death were censored at the last tumor assessment date. Data for patients with no postbaseline tumor assessments were censored at the randomization date.	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).
Secondary	Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1	Overall Response Rate (ORR) is defined as the proportion of participants who had an objective response (complete response [CR] or partial response [PR]) on two consecutive occasions at least 4 weeks apart according to RECIST v1.1. in the ORR evaluable population, defined as patients with measurable disease at baseline.	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).
Secondary	Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1	Overall Response Rate (ORR) is defined as the proportion of participants who had an objective response (complete response [CR] or partial response [PR]) on two consecutive occasions at least 4 weeks apart according to RECIST v1.1. in the ORR evaluable population, defined as patients with measurable disease at baseline.	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).
Secondary	Investigator-assessed Duration of Response (DOR) (INV-DOR) According to RECIST v1.1	Duration of Response (DOR) is defined as the time from the first occurrence of a confirmed objective response (complete response [CR] or partial response [PR]) to disease progression, or death, whichever occurs first. Data for participants who have not experienced disease progression or death will be censored at the last tumor assessment date. If no tumor assessments were performed after the date of the first occurrence of CR or PR, data for DOR will be censored at the date of the first occurrence of CR or PR.	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)
Secondary	Independent Review Facility (IRF)-Assessed Duration of Response (DOR) (IRF-DOR) According to RECIST v1.1	Duration of Response (DOR) is defined as the time from the first occurrence of a confirmed objective response (complete response [CR] or partial response [PR]) to disease progression, or death, whichever occurs first. Data for participants who have not experienced disease progression or death will be censored at the last tumor assessment date. If no tumor assessments were performed after the date of the first occurrence of CR or PR, data for DOR will be censored at the date of the first occurrence of CR or PR.	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)