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

Metastatic Renal Cell Carcinoma Clinical Trial

— CANTATA  

Official title:

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial Comparing CB-839 in Combination With Cabozantinib (CB-Cabo) vs. Placebo With Cabozantinib (Pbo-Cabo) in Patients With Advanced or Metastatic Renal Cell Carcinoma (RCC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03428217
• Other study ID #: CX-839-008
• Status: Completed
• Phase: Phase 2
• Start date: April 24, 2018
• Est. completion date: July 16, 2021

Study information

• Verified date: February 2023
• Source: Calithera Biosciences, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 444
• Est. completion date: July 16, 2021
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Documented histological or cytological diagnosis of renal cell carcinoma with a clear-cell component

2. Adult patients

3. Karnofsky Performance Score (KPS) = 70%

4. Measurable Disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

5. 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

6. Adequate hepatic, renal, cardiac and hematologic function

Exclusion Criteria:

1. Prior treatment with cabozantinib (or other mesenchymal-epithelial transition [MET] inhibitor) or CB-839

2. Receipt of other anticancer therapy within 2-6 weeks, depending on the treatment

3. Untreated or active brain metastases or central nervous system cancer, as defined per protocol

4. Prior gastric surgery, small bowel resection, or other conditions that may impede adequate absorption of oral study drug

5. Known active infection with human immunodeficiency virus (HIV), Hepatitis B or C virus

6. Inability to discontinue proton-pump-inhibitor use before randomization

7. Patients who are pregnant or lactating

Related Conditions & MeSH terms

• Advanced Renal Cell Carcinoma
• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma

Intervention

Drug:
• CB-839
Oral glutaminase inhibitor
• Cabozantinib
Oral receptor tyrosine kinase inhibitor
• Placebo
Placebo tablets

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Calithera Biosciences, Inc

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Italy,  New Zealand,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	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.	Up to the primary analysis data cut-off date of 31 Aug 2020. Maximum duration of follow-up for OS was 25.86 months.
Secondary	PFS as Assessed by the Investigator	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 22.64 months.