CANTATA: CB-839 With Cabozantinib vs. Cabozantinib With Placebo in Patients With Metastatic Renal Cell Carcinoma

Phase 2

Completed

Conditions: Advanced Renal Cell Carcinoma
Metastatic Renal Cell Carcinoma

Interventions: Drug: CB-839
Drug: Cabozantinib
Drug: Placebo

Registration Number: NCT03428217

Lead Sponsor: Calithera Biosciences, Inc

Brief Summary: Tthe primary objective of this study is to compare blinded Independent Radiology Committee (IRC)-adjudicated progression free survival (PFS) of patients treated with CB-839 + cabozantinib (CB-Cabo) versus placebo + cabozantinib (Pbo-Cabo) for advanced or metastatic clear-cell RCC (ccRCC).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 444

Inclusion Criteria

Documented histological or cytological diagnosis of renal cell carcinoma with a clear-cell component
Adult patients
Karnofsky Performance Score (KPS) ≥ 70%
Measurable Disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
1-2 lines of prior therapy for advanced or metastatic renal cell carcinoma (RCC) including one anti-angiogenic therapy (any vascular endothelial growth factor [VEGF] pathway-targeted agent used either as monotherapy or as a component of a combination regimen) OR the combination regimen of nivolumab + ipilimumab
Adequate hepatic, renal, cardiac and hematologic function

Exclusion Criteria

Prior treatment with cabozantinib (or other mesenchymal-epithelial transition [MET] inhibitor) or CB-839
Receipt of other anticancer therapy within 2-6 weeks, depending on the treatment
Untreated or active brain metastases or central nervous system cancer, as defined per protocol
Prior gastric surgery, small bowel resection, or other conditions that may impede adequate absorption of oral study drug
Known active infection with human immunodeficiency virus (HIV), Hepatitis B or C virus
Inability to discontinue proton-pump-inhibitor use before randomization
Patients who are pregnant or lactating

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pbo-Cabo	Placebo	Placebo twice daily (BID) + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or unacceptable toxicity, whichever occurred first.
CB-Cabo	CB-839	CB-839 800 mg BID + cabozantinib (60 mg QD) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.
Pbo-Cabo	Cabozantinib	Placebo twice daily (BID) + cabozantinib (60 mg once daily \[QD\]) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or unacceptable toxicity, whichever occurred first.
CB-Cabo	Cabozantinib	CB-839 800 mg BID + cabozantinib (60 mg QD) administered orally on Days 1 through 28 of each 28-day cycle until disease progression per RECIST v1.1 or unacceptable toxicity, whichever occurred first.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) as Assessed by the Independent Radiology Committee (IRC)	Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for PFS was 22.14 months.	PFS is defined as the time from randomization to the occurrence of disease progression as assessed by the IRC using RECIST v1.1 or death from any cause, whichever occurs first. Subjects not experiencing disease progression or death at the time of analysis of PFS will be censored at the date of the last evaluable radiographic disease assessment. RECIST v1.1 criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for OS was 25.86 months.	OS is defined as the time from randomization to death due to any cause. Estimated from Kaplan-Meier methodology. 95% confidence interval (CI) based on Brookmeyer-Crowley methodology.
PFS as Assessed by the Investigator	Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for PFS was 22.64 months.	PFS is defined as the time from randomization to the occurrence of disease progression as assessed by the IRC using RECIST v1.1 or death from any cause, whichever occurs first. Subjects not experiencing disease progression or death at the time of analysis of PFS will be censored at the date of the last evaluable radiographic disease assessment. RECIST v1.1 criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Trial Locations

Locations (132): NorthShore University HealthSystem
🇺🇸
Evanston, Illinois, United States
Orchard Healthcare Research, Inc.
🇺🇸
Skokie, Illinois, United States
University of Maryland, Greenebaum Comprehensive Cancer Center
🇺🇸
Baltimore, Maryland, United States
Mercy Hospital
🇺🇸
Joplin, Missouri, United States
Stony Brook Cancer Center
🇺🇸
Stony Brook, New York, United States
University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸
Miami, Florida, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Northern Westchester Hospital
🇺🇸
Mount Kisco, New York, United States
Chris O'Brien Lifehouse
🇦🇺
Camperdown, New South Wales, Australia
San Juan Oncology Associates, PC
🇺🇸
Farmington, New Mexico, United States
Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Allegheny General Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
The University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
West Cancer Center
🇺🇸
Germantown, Tennessee, United States
Centre Léon Bérard
🇫🇷
Lyon, France
Hattiesburg Clinic Hematology/Oncology
🇺🇸
Hattiesburg, Mississippi, United States
Comprehensive Cancer Centers of Nevada
🇺🇸
Las Vegas, Nevada, United States
North Shore Hematology Oncology Associates PC dba NY Cancer and Blood Specialists
🇺🇸
East Setauket, New York, United States
Auckland City Hospital
🇳🇿
Auckland, Grafton, New Zealand
HGU Gregorio Marañon
🇪🇸
Madrid, Spain
Hospital Universitari VHIO - Vall d'Hebron Departamento de Oncologia
🇪🇸
Barcelona, Spain
Wellington Regional Hospital
🇳🇿
Wellington, New Zealand
The Center for Cancer and Blood Disorders
🇺🇸
Fort Worth, Texas, United States
S.C. Oncologia - ASST Cremona P.O. Ospedale di Cremona
🇮🇹
Cremona, Italy
The Christie NHS Foundation Trust
🇬🇧
Manchester, Greater Manchester, United Kingdom
MD Anderson Cancer Center Madrid
🇪🇸
Madrid, Spain
Policlinico Universitario A. Gemelli
🇮🇹
Roma, Italy
Presidio Ospedaliero Antonio Perrino - U.O.C. Oncologia Medica
🇮🇹
Brindisi, Italy
Institut Català d'Oncologia
🇪🇸
Girona, Spain
Waikato Hospital
🇳🇿
Hamilton, New Zealand
Cairns Hospital
🇦🇺
Cairns, Queensland, Australia
Hospital de la Santa Creu i Sant Pau
🇪🇸
Barcelona, Spain
U.O.C. ASST Santi Paolo e Carlo - Ospedale San Carlo Borromeo
🇮🇹
Milano, Italy
Azienda Ospedaliero Universitaria San Luigi Gonzaga
🇮🇹
Orbassano, Italy
Christchurch Hospital
🇳🇿
Christchurch, South Island, New Zealand
Istituto Europeo di Oncologia - Divisione di Oncologia Medica Urogenitale e Cervico Facciale
🇮🇹
Milan, Italy
U.O. Oncologia Ospedale degli Infermi - Dipartimento di Oncologia ed Ematologia
🇮🇹
Rimini, Italy
Hospital Parc Taulí de Sabadell
🇪🇸
Sabadell, Spain
Institut Català d'Oncologia (ICO) L'Hospitalet
🇪🇸
Barcelona, Spain
St. Bartholomew's Hospital, Barts Health NHS Trust
🇬🇧
London, United Kingdom
Sarah Cannon Research Institute UK Limited
🇬🇧
London, United Kingdom
Fundación Instituto Valencia d'Oncología (IVO)
🇪🇸
Valencia, Spain
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹
Milan, Italy
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
🇮🇹
Naples, Italy
Unità Operativa (UO) di Oncologia Medica - ICS Maugeri
🇮🇹
Pavia, Italy
Centro Integral Oncologico Clara Campal (CIOCC) HM
🇪🇸
Madrid, Spain
Southampton General Hospital
🇬🇧
Southampton, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧
London, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧
Glasgow, Lanarkshire, United Kingdom
Hollywood Private Hospital
🇦🇺
Nedlands, Western Australia, Australia
University of Modena and Reggio Emilia (Azienda Ospedaliera-Universitaria Policlinico Modena)
🇮🇹
Modena, Italy
Policlinico Universitario Campus Bio-Medico
🇮🇹
Rome, Italy
Nottingham University Hospitals NHS Trust - City Hospital Campus
🇬🇧
Nottingham, Nottinghamshire, United Kingdom
Technischen Universitat München - Urologische Klinik
🇩🇪
München, Bavaria, Germany
NYU Winthrop Hospital
🇺🇸
Mineola, New York, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Centre Georges-François Leclerc
🇫🇷
Dijon, France
Centre Antoine Lacassagne
🇫🇷
Nice, France
Institut de Cancérologie de l'Ouest (ICO) - Centre René Gauducheau
🇫🇷
Saint-Herblain, France
Institut Gustave Roussy - Le département de Medecine oncologique
🇫🇷
Villejuif Cedex, France
The Sarah Cannon Research Institute
🇺🇸
Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Mayo Clinic Cancer Center
🇺🇸
Phoenix, Arizona, United States
Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Froedtert Hospital and the Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
University of Utah, Huntsman Cancer Institute
🇺🇸
Salt Lake City, Utah, United States
INTEGRIS Cancer Institute of Oklahoma Proton Campus
🇺🇸
Oklahoma City, Oklahoma, United States
Emory Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
El Hospital Clínic i Provincial de Barcelona (HCPB)
🇪🇸
Barcelona, Spain
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
🇺🇸
Los Angeles, California, United States
The University of Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
Stanford Cancer Center
🇺🇸
Palo Alto, California, United States
Salinas Valley Memorial Healthcare System
🇺🇸
Salinas, California, United States
Penrose Cancer Center, Research Department
🇺🇸
Colorado Springs, Colorado, United States
St. Joseph Heritage Healthcare
🇺🇸
Santa Rosa, California, United States
Georgetown University Medical Center
🇺🇸
Washington, District of Columbia, United States
Florida Cancer Specialists
🇺🇸
Saint Petersburg, Florida, United States
Georgia Cancer Center at Augusta University
🇺🇸
Augusta, Georgia, United States
Northwest Georgia Oncology Centers, PC
🇺🇸
Marietta, Georgia, United States
St. Luke's Mountain States Tumor Institute
🇺🇸
Boise, Idaho, United States
Centre Jean Perrin
🇫🇷
Clermont Ferrand, France
AMITA Health Cancer Institute & Outpatient Center
🇺🇸
Hinsdale, Illinois, United States
East Jefferson General Hospital
🇺🇸
Metairie, Louisiana, United States
Goshen Center for Cancer Care
🇺🇸
Goshen, Indiana, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸
Warrenville, Illinois, United States
HealthPartners Institute, Regions Cancer Care Center
🇺🇸
Saint Paul, Minnesota, United States
Roswell Park Cancer Center
🇺🇸
Buffalo, New York, United States
Saint Francis Hospital Cancer Center
🇺🇸
Greenville, South Carolina, United States
Kadlec Clinic Hematology and Oncology
🇺🇸
Kennewick, Washington, United States
Pindara Private Hospital
🇦🇺
Benowa, Queensland, Australia
Southern Highlands Private Hospital (Cancer Centre)
🇦🇺
Bowral, New South Wales, Australia
Liverpool Hospital
🇦🇺
Sydney, New South Wales, Australia
MacQuarie University Hospital
🇦🇺
North Ryde, New South Wales, Australia
Mater Misericordiae Limited - Division of Cancer Services
🇦🇺
South Brisbane, Queensland, Australia
Princess Alexandra Hospital
🇦🇺
Woolloongabba, Queensland, Australia
Ballarat Health Services
🇦🇺
Ballarat, Victoria, Australia
Cabrini Hospital
🇦🇺
Malvern, Victoria, Australia
Peninsula Private Hospital
🇦🇺
Frankston, Victoria, Australia
Goulburn Valley Health
🇦🇺
Shepparton, Victoria, Australia
CHU de Bordeaux Hôpital Saint André
🇫🇷
Bordeaux, France
Centre hospitalier régional universitaire (CHRU) de Besançon - Jean-Minjoz
🇫🇷
Besançon, France
Centre François Baclesse
🇫🇷
Caen Cedex 5, France
Centre hospitalier universitaire (CHU) Henri-Mondor
🇫🇷
Créteil, France
Institut Paoli-Calmettes Service d'Urologie
🇫🇷
Marseille, France
Institut de Cancérologie de Montpellier (ICM)
🇫🇷
Montpellier, France
Hôpital Européen Georges-Pompidou (HEGP)
🇫🇷
Paris, France
CHU de Strasbourg (Les Hôpitaux Universitaires de Strasbourg)
🇫🇷
Strasbourg, France
Institut de Cancérologie de Lorraine
🇫🇷
Vandœuvre-lès-Nancy, France
IUCTO Bureau des Essais Cliniques (Institut Claudius Regaud)
🇫🇷
Toulouse, France
Medical University Heidelberg, NCT (National Center for Tumour Diseases), Medical Oncology
🇩🇪
Heidelberg, Baden-Wuerttemberg, Germany
Charité Universitätsmedizin Berlin, Dept. of Interdisciplinary Urology
🇩🇪
Berlin, Germany
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Klinik und Poliklinik
🇩🇪
Dresden, Germany
Universitätsklinikum Essen (AöR) Westdeutsches Tumorzentrum
🇩🇪
Essen, Germany
Medizinische Hochschule Hannover
🇩🇪
Hannover, Germany
Universitätsklinikum Tübingen, Klinik für Urologie
🇩🇪
Tübingen, Germany
Hospital Universitario Virgen del Rocío
🇪🇸
Seville, Andalucia, Spain
El Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Hospital Universitario Virgen de Macarena
🇪🇸
Seville, Spain
Mount Vernon Cancer Centre
🇬🇧
London, Middlesex, United Kingdom
Tweed Hospital
🇦🇺
Tweed Heads, New South Wales, Australia
H.Lee Moffitt Cancer & Research Institute (Moffitt Cancer Center)
🇺🇸
Tampa, Florida, United States
Ochsner Clinic Foundation
🇺🇸
New Orleans, Louisiana, United States
HCA Midwest Health
🇺🇸
Kansas City, Missouri, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States