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

NCT03428217 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CX-839-008
• Study Type: interventional
• Target: 444
• Locations: 8 countries
• Sites: 133

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).

Conditions

Advanced Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma

Keywords

Tumor Metabolism; RCC; Glutaminase Inhibitor; CB-839; CANTATA; TKI; Tyrosine Kinase Inhibitor; cabozantinib; Cabometyx; Cometriq; glutaminase; glutamine; renal cell; clear cell; kidney cancer; cMET; MET; HGFR; telaglenastat

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) as Assessed by the Independent Radiology Committee (IRC)

  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.

  Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for PFS was 22.14 months.

Secondary Outcomes (2)

• 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.

• 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.

Study Arms (2)

Pbo-Cabo

PLACEBO COMPARATOR

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.

Drug: Cabozantinib; Drug: Placebo

CB-Cabo

EXPERIMENTAL

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.

Drug: CB-839; Drug: Cabozantinib

Interventions

CB-839 DRUG

Oral glutaminase inhibitor

Also known as: telaglenastat

CB-Cabo

Cabozantinib DRUG

Oral receptor tyrosine kinase inhibitor

Also known as: Cabometyx, Cabometriq

CB-Cabo; Pbo-Cabo

Placebo DRUG

Placebo tablets

Pbo-Cabo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Calithera Biosciences, Inc: lead

Study Sites (133)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic Cancer Center

Phoenix, Arizona, 85054, United States

Location

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

Location

Stanford Cancer Center

Palo Alto, California, 94304, United States

Location

Salinas Valley Memorial Healthcare System

Salinas, California, 93901, United States

Location

St. Joseph Heritage Healthcare

Santa Rosa, California, 95403, United States

Location

Penrose Cancer Center, Research Department

Colorado Springs, Colorado, 80907, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Florida Cancer Specialists

St. Petersburg, Florida, 33705, United States

Location

H.Lee Moffitt Cancer & Research Institute (Moffitt Cancer Center)

Tampa, Florida, 33612, United States

Location

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

Location

Northwest Georgia Oncology Centers, PC

Marietta, Georgia, 30060, United States

Location

St. Luke's Mountain States Tumor Institute

Boise, Idaho, 83712, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

NorthShore University HealthSystem

Evanston, Illinois, 60201, United States

Location

AMITA Health Cancer Institute & Outpatient Center

Hinsdale, Illinois, 60521, United States

Location

Orchard Healthcare Research, Inc.

Skokie, Illinois, 60077, United States

Location

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, 60555, United States

Location

Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

Location

East Jefferson General Hospital

Metairie, Louisiana, 70006, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

University of Maryland, Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

HealthPartners Institute, Regions Cancer Care Center

Saint Paul, Minnesota, 55101, United States

Location

Hattiesburg Clinic Hematology/Oncology

Hattiesburg, Mississippi, 39401, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Mercy Hospital

Joplin, Missouri, 64804, United States

Location

HCA Midwest Health

Kansas City, Missouri, 64132, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89148, United States

Location

San Juan Oncology Associates, PC

Farmington, New Mexico, 87401, United States

Location

Roswell Park Cancer Center

Buffalo, New York, 14263, United States

Location

North Shore Hematology Oncology Associates PC dba NY Cancer and Blood Specialists

East Setauket, New York, 11733, United States

Location

NYU Winthrop Hospital

Mineola, New York, 11501, United States

Location

Northern Westchester Hospital

Mount Kisco, New York, 10549, United States

Location

Stony Brook Cancer Center

Stony Brook, New York, 11794, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

INTEGRIS Cancer Institute of Oklahoma Proton Campus

Oklahoma City, Oklahoma, 73142, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Saint Francis Hospital Cancer Center

Greenville, South Carolina, 29607, United States

Location

West Cancer Center

Germantown, Tennessee, 38138, United States

Location

The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, 99336, United States

Location

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Southern Highlands Private Hospital (Cancer Centre)

Bowral, New South Wales, 2576, Australia

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

MacQuarie University Hospital

North Ryde, New South Wales, 2109, Australia

Location

Liverpool Hospital

Sydney, New South Wales, 2170, Australia

Location

Tweed Hospital

Tweed Heads, New South Wales, 2485, Australia

Location

Pindara Private Hospital

Benowa, Queensland, 4217, Australia

Location

Cairns Hospital

Cairns, Queensland, 4870, Australia

Location

Mater Misericordiae Limited - Division of Cancer Services

South Brisbane, Queensland, 4101, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Ballarat Health Services

Ballarat, Victoria, 3350, Australia

Location

Peninsula Private Hospital

Frankston, Victoria, 3199, Australia

Location

Cabrini Hospital

Malvern, Victoria, 3144, Australia

Location

Goulburn Valley Health

Shepparton, Victoria, 3630, Australia

Location

Hollywood Private Hospital

Nedlands, Western Australia, 6009, Australia

Location

Centre hospitalier régional universitaire (CHRU) de Besançon - Jean-Minjoz

Besançon, 25030, France

Location

CHU de Bordeaux Hôpital Saint André

Bordeaux, 33000, France

Location

Centre François Baclesse

Caen, 14076, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre hospitalier universitaire (CHU) Henri-Mondor

Créteil, 94010, France

Location

Centre Georges-François Leclerc

Dijon, 21079, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Institut Paoli-Calmettes Service d'Urologie

Marseille, 13009, France

Location

Institut de Cancérologie de Montpellier (ICM)

Montpellier, 34298, France

Location

Centre Antoine Lacassagne

Nice, 06189 Nice Cedex 2, France

Location

Hôpital Européen Georges-Pompidou (HEGP)

Paris, 75015, France

Location

Institut de Cancérologie de l'Ouest (ICO) - Centre René Gauducheau

Saint-Herblain, 44805, France

Location

CHU de Strasbourg (Les Hôpitaux Universitaires de Strasbourg)

Strasbourg, 67091, France

Location

IUCTO Bureau des Essais Cliniques (Institut Claudius Regaud)

Toulouse, 31059, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, CS 30519 54519, France

Location

Institut Gustave Roussy - Le département de Medecine oncologique

Villejuif, 94805, France

Location

Medical University Heidelberg, NCT (National Center for Tumour Diseases), Medical Oncology

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Technischen Universitat München - Urologische Klinik

München, Bavaria, 81675, Germany

Location

Charité Universitätsmedizin Berlin, Dept. of Interdisciplinary Urology

Berlin, 10117, Germany

Location

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Klinik und Poliklinik

Dresden, 01307, Germany

Location

Universitätsklinikum Essen (AöR) Westdeutsches Tumorzentrum

Essen, 45147, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Tübingen, Klinik für Urologie

Tübingen, 72076, Germany

Location

Presidio Ospedaliero Antonio Perrino - U.O.C. Oncologia Medica

Brindisi, 72100, Italy

Location

S.C. Oncologia - ASST Cremona P.O. Ospedale di Cremona

Cremona, 26100, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Europeo di Oncologia - Divisione di Oncologia Medica Urogenitale e Cervico Facciale

Milan, 20141, Italy

Location

U.O.C. ASST Santi Paolo e Carlo - Ospedale San Carlo Borromeo

Milan, 20153, Italy

Location

University of Modena and Reggio Emilia (Azienda Ospedaliera-Universitaria Policlinico Modena)

Modena, 41124, Italy

Location

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

Naples, 80131, Italy

Location

Azienda Ospedaliero Universitaria San Luigi Gonzaga

Orbassano, 10043, Italy

Location

Unità Operativa (UO) di Oncologia Medica - ICS Maugeri

Pavia, 27100, Italy

Location

U.O. Oncologia Ospedale degli Infermi - Dipartimento di Oncologia ed Ematologia

Rimini, 47923, Italy

Location

Policlinico Universitario A. Gemelli

Roma, 00168, Italy

Location

Policlinico Universitario Campus Bio-Medico

Rome, 00128, Italy

Location

Auckland City Hospital

Auckland, Grafton, 1023, New Zealand

Location

Christchurch Hospital

Christchurch, South Island, 8011, New Zealand

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

Wellington Regional Hospital

Wellington, 6021, New Zealand

Location

Hospital Universitario Virgen del Rocío

Seville, Andalusia, 41013, Spain

Location

Hospital Universitari VHIO - Vall d'Hebron Departamento de Oncologia

Barcelona, 08035, Spain

Location

El Hospital Clínic i Provincial de Barcelona (HCPB)

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Institut Català d'Oncologia (ICO) L'Hospitalet

Barcelona, 08908, Spain

Location

Institut Català d'Oncologia

Girona, 17007, Spain

Location

HGU Gregorio Marañon

Madrid, 28009, Spain

Location

MD Anderson Cancer Center Madrid

Madrid, 28033, Spain

Location

El Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Centro Integral Oncologico Clara Campal (CIOCC) HM

Madrid, 28050, Spain

Location

Hospital Parc Taulí de Sabadell

Sabadell, 08208, Spain

Location

Hospital Universitario Virgen de Macarena

Seville, 41009, Spain

Location

Fundación Instituto Valencia d'Oncología (IVO)

Valencia, 46009, Spain

Location

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, Lanarkshire, G12 0YN, United Kingdom

Location

Mount Vernon Cancer Centre

London, Middlesex, HA6 2RN, United Kingdom

Location

Nottingham University Hospitals NHS Trust - City Hospital Campus

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

Location

St. Bartholomew's Hospital, Barts Health NHS Trust

London, EC1A7BE, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

Sarah Cannon Research Institute UK Limited

London, W1G 6AD, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• Tannir NM, Agarwal N, Porta C, Lawrence NJ, Motzer R, McGregor B, Lee RJ, Jain RK, Davis N, Appleman LJ, Goodman O Jr, Stadler WM, Gandhi S, Geynisman DM, Iacovelli R, Mellado B, Sepulveda Sanchez JM, Figlin R, Powles T, Akella L, Orford K, Escudier B. Efficacy and Safety of Telaglenastat Plus Cabozantinib vs Placebo Plus Cabozantinib in Patients With Advanced Renal Cell Carcinoma: The CANTATA Randomized Clinical Trial. JAMA Oncol. 2022 Oct 1;8(10):1411-1418. doi: 10.1001/jamaoncol.2022.3511.

  PMID: 36048457 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

CB-839; cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Study Director
• Organization: Calithera Biosciences, Inc

clinicaltrials@calithera.com

650-870-1000

Study Officials

• Sam Whiting, M.D., Ph.D.

  Calithera Biosciences, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, care providers, investigators and outcomes assessors are blinded to treatment. Progression free survival (PFS) will be assessed by a blinded Independent Radiology Committee for the primary endpoint of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a double blinded placebo-controlled study where patients will be randomized 1:1 to either CB-839 (telaglenastat) plus cabozantinib or placebo plus cabozantinib

Study Record Dates

• First Submitted: February 5, 2018
• First Posted: February 9, 2018
• Study Start: April 24, 2018
• Primary Completion: August 31, 2020
• Study Completion: July 16, 2021
• Last Updated: March 20, 2023
• Results First Posted: March 20, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (12); US (59); DE (7); ES (13); FR (16); NZ (4); GB (8); AU (14)