Study of Cabozantinib (XL184) Versus Prednisone in Men With Metastatic Castration-resistant Prostate Cancer Previously Treated With Docetaxel and Abiraterone or MDV3100

NCT ID: NCT01605227

Last Updated: 2018-03-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1028 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-07-31

Study Completion Date

2015-03-31

Brief Summary

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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.

Detailed Description

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Conditions

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Prostate Cancer Castration Resistant Prostate Cancer Pain Prostatic Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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cabozantinib

Subjects randomized to the cabozantinib arm will also receive placebo-matched prednisone capsules.

Group Type EXPERIMENTAL

cabozantinib

Intervention Type DRUG

Tablets taken orally once-daily

prednisone

Subjects randomized to the prednisone arm will also receive placebo-matched cabozantinib.

Group Type ACTIVE_COMPARATOR

prednisone

Intervention Type DRUG

Taken twice a day orally. Commercially-obtained prednisone tablets will be over-encapsulated in order to blind identity.

Interventions

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cabozantinib

Tablets taken orally once-daily

Intervention Type DRUG

prednisone

Taken twice a day orally. Commercially-obtained prednisone tablets will be over-encapsulated in order to blind identity.

Intervention Type DRUG

Other Intervention Names

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XL184

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Exelixis

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Birmingham, Alabama, United States

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Anchorage, Alaska, United States

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Phoenix, Arizona, United States

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Scottsdale, Arizona, United States

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Tucson, Arizona, United States

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Jonesboro, Arkansas, United States

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Duarte, California, United States

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Highland, California, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Montebello, California, United States

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Orange, California, United States

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Palo Alto, California, United States

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Rancho Mirage, California, United States

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San Marcos, California, United States

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St. Helena, California, United States

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Vallejo, California, United States

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Aurora, Colorado, United States

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New Haven, Connecticut, United States

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Southington, Connecticut, United States

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Miami Beach, Florida, United States

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Ocala, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Titusville, Florida, United States

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Wellington, Florida, United States

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West Palm Beach, Florida, United States

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Athens, Georgia, United States

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Atlanta, Georgia, United States

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Marietta, Georgia, United States

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Galesburg, Illinois, United States

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Niles, Illinois, United States

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Ames, Iowa, United States

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Sioux City, Iowa, United States

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Wichita, Kansas, United States

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Hazard, Kentucky, United States

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Louisville, Kentucky, United States

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Brewer, Maine, United States

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Baltimore, Maryland, United States

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Bethesda, Maryland, United States

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Towson, Maryland, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Methuen, Massachusetts, United States

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Detroit, Michigan, United States

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Wyoming, Michigan, United States

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Minneapolis, Minnesota, United States

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Jefferson City, Missouri, United States

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Springfield, Missouri, United States

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Lincoln, Nebraska, United States

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Omaha, Nebraska, United States

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Hackensack, New Jersey, United States

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Lawrenceville, New Jersey, United States

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Albany, New York, United States

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Garden City, New York, United States

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New York, New York, United States

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Pinehurst, North Carolina, United States

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Bismarck, North Dakota, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Portland, Oregon, United States

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Bryn Mawr, Pennsylvania, United States

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Hershey, Pennsylvania, United States

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Lancaster, Pennsylvania, United States

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Greenville, South Carolina, United States

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Chattanooga, Tennessee, United States

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Amarillo, Texas, United States

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Bedford, Texas, United States

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Houston, Texas, United States

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Laredo, Texas, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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Burlington, Vermont, United States

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Fairfax, Virginia, United States

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Newport News, Virginia, United States

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Spokane, Washington, United States

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Green Bay, Wisconsin, United States

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Albury, New South Wales, Australia

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Concord, New South Wales, Australia

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Darlinghurst, New South Wales, Australia

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Kogarah, New South Wales, Australia

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Port Macquarie, New South Wales, Australia

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Randwick, New South Wales, Australia

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Wahroonga, New South Wales, Australia

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Westmead, New South Wales, Australia

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South Brisbane, Queensland, Australia

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Southport, Queensland, Australia

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Woolloongabba, Queensland, Australia

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Adelaide, South Australia, Australia

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Kurralta Park, South Australia, Australia

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Hobart, Tasmania, Australia

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Bentleigh East, Victoria, Australia

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Box Hill, Victoria, Australia

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Wodonga, Victoria, Australia

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Perth, Western Australia, Australia

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Linz, , Austria

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Salzburg, , Austria

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Vienna, , Austria

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Wein, , Austria

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Aalst, , Belgium

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Bonheiden, , Belgium

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Brussels, , Belgium

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Brussels, , Belgium

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Brussels, , Belgium

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Ghent, , Belgium

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Hasselt, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Roeselare, , Belgium

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Calgary, Alberta, Canada

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Vancouver, British Columbia, Canada

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Miramichi, New Brunswick, Canada

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Halifax, Nova Scotia, Canada

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London, Ontario, Canada

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Owen Sound, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, , Canada

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Angers, , France

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Besançon, , France

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Bordeaux, , France

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Caen, , France

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Clermont-Ferrand, , France

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Dijon, , France

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La Roche-sur-Yon, , France

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Le Mans, , France

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Lille, , France

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Lyon, , France

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Marseille, , France

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Nancy, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Pierre-Bénite, , France

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Rennes, , France

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Saint-Herblain, , France

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Strasbourg, , France

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Suresnes, , France

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Villejuif, , France

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Aachen, , Germany

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Aachen, , Germany

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Berlin, , Germany

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Berlin, , Germany

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Braunschweig, , Germany

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Cologne, , Germany

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Dresden, , Germany

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Düsseldorf, , Germany

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Frankfurt am Main, , Germany

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Freiburg im Breisgau, , Germany

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Fürth, , Germany

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Gütersloh, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Homburg, , Germany

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Kassel, , Germany

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Kempen, , Germany

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Kirchheim, , Germany

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Mannheim, , Germany

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München, , Germany

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Münster, , Germany

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Nürtingen, , Germany

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Offenburg, , Germany

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Traunstein, , Germany

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Tübingen, , Germany

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Weiden, , Germany

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Wuppertal, , Germany

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Cork, , Ireland

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Dublin, , Ireland

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Dublin, , Ireland

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Galway, , Ireland

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Ancona, , Italy

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Arezzo, , Italy

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Aviano, , Italy

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Brindisi, , Italy

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Cremona, , Italy

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Genova, , Italy

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Livorno, , Italy

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Meldola, , Italy

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Milan, , Italy

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Milan, , Italy

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Milan, , Italy

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Modena, , Italy

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Napoli, , Italy

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Novara, , Italy

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Orbassano, , Italy

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Padua, , Italy

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Pavia, , Italy

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Pisa, , Italy

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Pordenone, , Italy

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Ravenna, , Italy

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Rimini, , Italy

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Roma, , Italy

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Roma, , Italy

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Rozzano, , Italy

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Terni, , Italy

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Torino, , Italy

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Verona, , Italy

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Amsterdam, , Netherlands

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Groningen, , Netherlands

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Groningen, , Netherlands

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Hoofddorp, , Netherlands

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Nieuwegein, , Netherlands

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Nijmegen, , Netherlands

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Rotterdam, , Netherlands

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Rotterdam, , Netherlands

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Tilburg, , Netherlands

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Zwolle, , Netherlands

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Ponce, , Puerto Rico

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Málaga, Andalusia, Spain

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Seville, Andalusia, Spain

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Palma de Mallorca, Balearic Islands, Spain

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San Cristóbal de La Laguna, Canary Islands, Spain

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Badalona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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L'Hospitalet de Llobregat, Catalonia, Spain

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Manresa, Catalonia, Spain

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A Coruña, Galicia, Spain

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Santiago de Compostela, Galicia, Spain

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Madrid, Madrid, Communidad de, Spain

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Madrid, Madrid, Communidad de, Spain

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Madrid, Madrid, Communidad de, Spain

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Madrid, Madrid, Communidad de, Spain

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Madrid, Madrid, Communidad de, Spain

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Majadahonda, Madrid, Communidad de, Spain

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Pamplona, Navarre, Spain

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Oviedo, Principality of Asturias, Spain

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Elche, Valencia, Spain

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Valencia, Valencia, Spain

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Gotenborg, , Sweden

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Malmo, , Sweden

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Örebro, , Sweden

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Stockholm, , Sweden

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Umeå, , Sweden

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Uppsala, , Sweden

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Vaxjo, , Sweden

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Aberdeen, , United Kingdom

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Bath, , United Kingdom

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Birmingham, , United Kingdom

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Brighton, , United Kingdom

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Bristol, , United Kingdom

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Cambridge, , United Kingdom

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Cardiff, , United Kingdom

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Cottingham, , United Kingdom

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Edinburgh, , United Kingdom

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Inverness, , United Kingdom

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Lancaster, , United Kingdom

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Leeds, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Maidstone, , United Kingdom

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Metropolitan Borough of Wirral, , United Kingdom

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Northwood, , United Kingdom

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Plymouth, , United Kingdom

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Sheffield, , United Kingdom

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Southampton, , United Kingdom

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Sutton, , United Kingdom

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Countries

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United States Australia Austria Belgium Canada France Germany Ireland Italy Netherlands Puerto Rico Spain Sweden United Kingdom

References

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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.

Reference Type DERIVED
PMID: 29272162 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27400947 (View on PubMed)

Other Identifiers

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2012-001834-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

XL184-307

Identifier Type: -

Identifier Source: org_study_id

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