Clinical trial NCT01605227: Study of Cabozantinib (XL184) Versus Prednisone in Men With Metastatic Castration-resistant Prostate Cancer Previously Treated With Docetaxel and Abiraterone or MDV3100
Official title: A Phase 3, Randomized, Double-blind, Controlled Study of Cabozantinib (XL184) Versus Prednisone in Metastatic Castration-resistant Prostate Cancer Patients Who Have Received Prior Docetaxel and Prior Abiraterone or MDV3100
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Castration Resistant Prostate Cancer
Pain
Prostatic Neoplasms
Keywords: prostate cancer
castration resistant prostate cancer
bone pain
CRPC
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2012-05-24
Enrollment: 1028
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the effect of cabozantinib compared to prednisone on overall survival in men with previously treated metastatic castration-resistant prostate cancer with bone-dominant disease who have experienced disease progression on docetaxel-containing chemotherapy and abiraterone or MDV3100.


Eligibility criteria: Inclusion Criteria:

* Histological or cytological diagnosis of castration resistant prostate cancer (serum testosterone less than 50 ng/dL).
* Evidence of bone metastasis related to prostate cancer on bone scans.
* Received prior docetaxel (minimum cumulative dose of 225 mg/m2) and either abiraterone or MDV3100 treatment and has evidence of prostate cancer progression on each agent independently.
* Maintenance of LHRH agonist or antagonist unless treated with orchiectomy.
* Recovered from toxicities related to any prior treatments, unless the toxicities are clinically non significant or easily manageable.
* Adequate organ and marrow function.
* Capable of understanding and complying with the protocol requirements and signed the informed consent form.
* Sexually active fertile patients and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment.

Exclusion Criteria:

* Prior treatment with cabozantinib.
* Treatment with docetaxel, abiraterone, or MDV3100 in the last 2 weeks; or with any other type of cytotoxic or investigational anticancer agent in the last 2 weeks.
* Radiation within 4 weeks (excluded if to mediastinum) or radionuclide treatment within 6 weeks of randomization.
* Known brain metastases or cranial epidural disease.
* Requires concomitant treatment, in therapeutic doses, with anticoagulants.
* Requires chronic concomitant treatment of strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's Wort).
* Uncontrolled, significant intercurrent illness including, but not limited to, cardiovascular disorders, gastrointestinal disorders, active infections, non-healing wounds, recent surgery.
* Clinically significant hematemesis or hemoptysis, or other signs indicative of pulmonary hemorrhage in the last 3 months, or history of other significant bleeding in the past 6 months.
* Cavitating pulmonary lesion(s) or a lesion invading or encasing a major blood vessel.
* QTcF \> 500 ms within 7 days of randomization.
* Unable to swallow capsules or tablets.
* Previously-identified allergy or hypersensitivity to components of the study treatment formulations.
* Another diagnosis of malignancy requiring systemic treatment within 2 years of randomization.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: OS was measured from the time of randomization until 614 events, approximately 24 months after study start
Secondary outcomes:
measure: Bone Scan Response (BSR)
timeFrame: BSR was measured at the end of Week 12 as determined by the IRF
Other outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Duration of PFS was defined as time from the date of randomization to earlier of date of radiographic progression (bone/andor soft tissue) according to the investigator's assessment or death, assessed for up to approximately 24 months
Locations:
city: Birmingham
country: United States
state: Alabama
city: Anchorage
country: United States
state: Alaska
city: Phoenix
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Jonesboro
country: United States
state: Arkansas
city: Duarte
country: United States
state: California
city: Highland
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Montebello
country: United States
state: California
city: Orange
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: Rancho Mirage
country: United States
state: California
city: Saint Helena
country: United States
state: California
city: San Marcos
country: United States
state: California
city: Vallejo
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: New Haven
country: United States
state: Connecticut
city: Southington
country: United States
state: Connecticut
city: Miami Beach
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Titusville
country: United States
state: Florida
city: Wellington
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Athens
country: United States
state: Georgia
city: Atlanta
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Galesburg
country: United States
state: Illinois
city: Niles
country: United States
state: Illinois
city: Ames
country: United States
state: Iowa
city: Sioux City
country: United States
state: Iowa
city: Wichita
country: United States
state: Kansas
city: Hazard
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Brewer
country: United States
state: Maine
city: Baltimore
country: United States
state: Maryland
city: Bethesda
country: United States
state: Maryland
city: Towson
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Methuen
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Wyoming
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Jefferson City
country: United States
state: Missouri
city: Springfield
country: United States
state: Missouri
city: Lincoln
country: United States
state: Nebraska
city: Omaha
country: United States
state: Nebraska
city: Hackensack
country: United States
state: New Jersey
city: Lawrenceville
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: Garden City
country: United States
state: New York
city: New York
country: United States
state: New York
city: Pinehurst
country: United States
state: North Carolina
city: Bismarck
country: United States
state: North Dakota
city: Cincinnati
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Bryn Mawr
country: United States
state: Pennsylvania
city: Hershey
country: United States
state: Pennsylvania
city: Lancaster
country: United States
state: Pennsylvania
city: Greenville
country: United States
state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
city: Amarillo
country: United States
state: Texas
city: Bedford
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Laredo
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Burlington
country: United States
state: Vermont
city: Fairfax
country: United States
state: Virginia
city: Newport News
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Green Bay
country: United States
state: Wisconsin
city: Albury
country: Australia
state: New South Wales
city: Concord
country: Australia
state: New South Wales
city: Darlinghurst
country: Australia
state: New South Wales
city: Kogarah
country: Australia
state: New South Wales
city: Port Macquarie
country: Australia
state: New South Wales
city: Randwick
country: Australia
state: New South Wales
city: Wahroonga
country: Australia
state: New South Wales
city: Westmead
country: Australia
state: New South Wales
city: South Brisbane
country: Australia
state: Queensland
city: Southport
country: Australia
state: Queensland
city: Woolloongabba
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Kurralta Park
country: Australia
state: South Australia
city: Hobart
country: Australia
state: Tasmania
city: Bentleigh East
country: Australia
state: Victoria
city: Box Hill
country: Australia
state: Victoria
city: Wodonga
country: Australia
state: Victoria
city: Perth
country: Australia
state: Western Australia
city: Linz
country: Austria
city: Salzburg
country: Austria
city: Wein
country: Austria
city: Wien
country: Austria
city: Aalst
country: Belgium
city: Bonheiden
country: Belgium
city: Brussels
country: Belgium
city: Brussels
country: Belgium
city: Brussels
country: Belgium
city: Gent
country: Belgium
city: Hasselt
country: Belgium
city: Leuven
country: Belgium
city: Liège
country: Belgium
city: Roeselare
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Miramichi
country: Canada
state: New Brunswick
city: Halifax
country: Canada
state: Nova Scotia
city: London
country: Canada
state: Ontario
city: Owen Sound
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Angers
country: France
city: Besançon
country: France
city: Bordeaux
country: France
city: Caen
country: France
city: Clermont Ferrand
country: France
city: Dijon
country: France
city: La Roche sur Yon
country: France
city: Le Mans
country: France
city: Lille
country: France
city: Lyon Cedex 08
country: France
city: Marseille
country: France
city: Nancy
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Pierre Benite
country: France
city: Rennes
country: France
city: Saint Herblain
country: France
city: Strasbourg
country: France
city: Suresnes
country: France
city: Villejuif Cedex
country: France
city: Aachen
country: Germany
city: Aachen
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Braunschweig
country: Germany
city: Dresden
country: Germany
city: Dusseldorf
country: Germany
city: Frankfurt am Main
country: Germany
city: Freiburg
country: Germany
city: Furth
country: Germany
city: Gütersloh
country: Germany
city: Hamburg
country: Germany
city: Hamburg
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Homburg
country: Germany
city: Kassel
country: Germany
city: Kempen
country: Germany
city: Kirchheim
country: Germany
city: Koln
country: Germany
city: Mannheim
country: Germany
city: Munchen
country: Germany
city: Munster
country: Germany
city: Nurtingen
country: Germany
city: Offenburg
country: Germany
city: Traunstein
country: Germany
city: Tubingen
country: Germany
city: Weiden
country: Germany
city: Wuppertal
country: Germany
city: Cork
country: Ireland
city: Dublin
country: Ireland
city: Dublin
country: Ireland
city: Galway
country: Ireland
city: Ancona
country: Italy
city: Arezzo
country: Italy
city: Aviano
country: Italy
city: Brindisi
country: Italy
city: Cremona
country: Italy
city: Genova
country: Italy
city: Livorno
country: Italy
city: Meldola
country: Italy
city: Milano
country: Italy
city: Milano
country: Italy
city: Milano
country: Italy
city: Modena
country: Italy
city: Napoli
country: Italy
city: Novara
country: Italy
city: Orbassano
country: Italy
city: Padova
country: Italy
city: Pavia
country: Italy
city: Pisa
country: Italy
city: Pordenone
country: Italy
city: Ravenna
country: Italy
city: Rimini
country: Italy
city: Roma
country: Italy
city: Roma
country: Italy
city: Rozzano
country: Italy
city: Terni
country: Italy
city: Torino
country: Italy
city: Verona
country: Italy
city: Amsterdam
country: Netherlands
city: Groningen
country: Netherlands
city: Groningen
country: Netherlands
city: Hoofddorp
country: Netherlands
city: Nieuwegein
country: Netherlands
city: Nijmegen
country: Netherlands
city: Rotterdam
country: Netherlands
city: Rotterdam
country: Netherlands
city: Tilburg
country: Netherlands
city: Zwolle
country: Netherlands
city: Ponce
country: Puerto Rico
city: Málaga
country: Spain
state: Andalucía
city: Sevilla
country: Spain
state: Andalucía
city: Oviedo
country: Spain
state: Asturias
city: Palma de Mallorca
country: Spain
state: Baleares
city: La Laguna
country: Spain
state: Canarias
city: Badalona
country: Spain
state: Cataluña
city: Barcelona
country: Spain
state: Cataluña
city: Barcelona
country: Spain
state: Cataluña
city: Barcelona
country: Spain
state: Cataluña
city: Barcelona
country: Spain
state: Cataluña
city: Barcelona
country: Spain
state: Cataluña
city: L'Hospitalet de Llobregat
country: Spain
state: Cataluña
city: Manresa
country: Spain
state: Cataluña
city: Elche
country: Spain
state: Comunidad Valenciana
city: Valencia
country: Spain
state: Comunidad Valenciana
city: A Coruña
country: Spain
state: Galicia
city: Santiago de Compostela
country: Spain
state: Galicia
city: Madrid
country: Spain
state: Madrid, Communidad De
city: Madrid
country: Spain
state: Madrid, Communidad De
city: Madrid
country: Spain
state: Madrid, Communidad De
city: Madrid
country: Spain
state: Madrid, Communidad De
city: Madrid
country: Spain
state: Madrid, Communidad De
city: Majadahonda
country: Spain
state: Madrid, Communidad De
city: Pamplona
country: Spain
state: Navarra
city: Gotenborg
country: Sweden
city: Malmo
country: Sweden
city: Orebro
country: Sweden
city: Stockholm
country: Sweden
city: Umea
country: Sweden
city: Uppsala
country: Sweden
city: Vaxjo
country: Sweden
city: Aberdeen
country: United Kingdom
city: Bath
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Brighton
country: United Kingdom
city: Bristol
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Cottingham
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Inverness
country: United Kingdom
city: Lancaster
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Maidstone
country: United Kingdom
city: Northwood
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Southampton
country: United Kingdom
city: Sutton
country: United Kingdom
city: Wirral
country: United Kingdom
Study officials:
References:
citation: Heller G, McCormack R, Kheoh T, Molina A, Smith MR, Dreicer R, Saad F, de Wit R, Aftab DT, Hirmand M, Limon A, Fizazi K, Fleisher M, de Bono JS, Scher HI. Circulating Tumor Cell Number as a Response Measure of Prolonged Survival for Metastatic Castration-Resistant Prostate Cancer: A Comparison With Prostate-Specific Antigen Across Five Randomized Phase III Clinical Trials. J Clin Oncol. 2018 Feb 20;36(6):572-580. doi: 10.1200/JCO.2017.75.2998. Epub 2017 Dec 22.
citation: Smith M, De Bono J, Sternberg C, Le Moulec S, Oudard S, De Giorgi U, Krainer M, Bergman A, Hoelzer W, De Wit R, Bogemann M, Saad F, Cruciani G, Thiery-Vuillemin A, Feyerabend S, Miller K, Houede N, Hussain S, Lam E, Polikoff J, Stenzl A, Mainwaring P, Ramies D, Hessel C, Weitzman A, Fizazi K. Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1. J Clin Oncol. 2016 Sep 1;34(25):3005-13. doi: 10.1200/JCO.2015.65.5597. Epub 2016 Jul 11.