Prostate CancerPhase 3COMET-1NCT01605227
Study of Cabozantinib (XL184) Versus Prednisone in Men With Metastatic Castration-resistant Prostate Cancer Previously Treated With Docetaxel and Abiraterone or MDV3100
A Phase 3 study testing cabozantinib and prednisone in people with Prostate Cancer and Castration Resistant Prostate Cancer, run by Exelixis at 264 sites in 14 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer, Castration Resistant Prostate Cancer, Pain
- What is being tested?
- cabozantinib and prednisone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,028 participants
- Where
- 264 sitesin 14 countries
- Study dates
- Jul 2012to Mar 2015
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
264 sites in 14 countries.
264 sites in 14 countries
United States77 sites
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Albany, New York, 12208
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Amarillo, Texas, 79106
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Ames, Iowa, 50010
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Anchorage, Alaska, 99508
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Athens, Georgia, 30607
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Atlanta, Georgia, 30318
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Aurora, Colorado, 80045
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Baltimore, Maryland, 21201
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Bedford, Texas, 76022
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Bethesda, Maryland, 20817
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Birmingham, Alabama, 35205
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Bismarck, North Dakota, 58501
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Boston, Massachusetts, 02114
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Boston, Massachusetts, 02118
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Brewer, Maine, 04412
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Bryn Mawr, Pennsylvania, 19010
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Burlington, Vermont, 05405
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Chattanooga, Tennessee, 37421
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Cincinnati, Ohio, 45219
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Columbus, Ohio, 43221
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Detroit, Michigan, 48202
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Duarte, California, 91010
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Fairfax, Virginia, 22031
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Galesburg, Illinois, 61401
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Garden City, New York, 11530
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Green Bay, Wisconsin, 54311
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Greenville, South Carolina, 29615
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Hackensack, New Jersey, 07601
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Hazard, Kentucky, 41701
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Hershey, Pennsylvania, 17033
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Highland, California, 92346
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Houston, Texas, 77024
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Jefferson City, Missouri, 65109
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Jonesboro, Arkansas, 72401
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La Jolla, California, 92093
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Lancaster, Pennsylvania, 17604
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Laredo, Texas, 78041
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Lawrenceville, New Jersey, 08648
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Lincoln, Nebraska, 68506
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Los Angeles, California, 90033
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Louisville, Kentucky, 40202
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Marietta, Georgia, 30060
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Methuen, Massachusetts, 01844
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Miami Beach, Florida, 33140
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Minneapolis, Minnesota, 55455
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Montebello, California, 90640
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New Haven, Connecticut, 06520
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New York, New York, 10065
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Newport News, Virginia, 23601
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Niles, Illinois, 60714
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Ocala, Florida, 34471
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Omaha, Nebraska, 68130
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Orange, California, 92868
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Orlando, Florida, 32806
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Palo Alto, California, 94301
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Phoenix, Arizona, 85016
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Pinehurst, North Carolina, 28374
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Portland, Oregon, 97227
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Rancho Mirage, California, 92270
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Salt Lake City, Utah, 84112
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San Antonio, Texas, 78217
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San Marcos, California, 92069
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Scottsdale, Arizona, 85255
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Sioux City, Iowa, 51101
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Southington, Connecticut, 06489
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Spokane, Washington, 99204
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Springfield, Missouri, 65804
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St. Helena, California, 94574
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Tampa, Florida, 33612
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Titusville, Florida, 32796
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Towson, Maryland, 21204
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Tucson, Arizona, 85710
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Vallejo, California, 94589
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Wellington, Florida, 33449
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West Palm Beach, Florida, 33401
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Wichita, Kansas, 67214
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Wyoming, Michigan, 49509
Germany30 sites
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Aachen, 52062
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Aachen, 52074
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Berlin, 12200
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Berlin, 13055
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Braunschweig, 38126
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Cologne, 50968
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Dresden, 01307
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Düsseldorf, 40225
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Frankfurt am Main, 60488
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Freiburg im Breisgau, 79106
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Fürth, 90766
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Gütersloh, 33332
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Hamburg, 20246
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Hamburg, 22399
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Hamburg, 22763
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Hanover, 30625
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Heidelberg, 69120
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Homburg, 66421
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Kassel, 34125
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Kempen, 47906
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Kirchheim, 73230
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Mannheim, 68167
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München, 81675
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Münster, 48149
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Nürtingen, 72622
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Offenburg, 77654
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Traunstein, 83278
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Tübingen, 72076
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Weiden, 92637
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Wuppertal, 42103
Italy27 sites
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Ancona, 60126
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Arezzo, 52100
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Aviano, 33081
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Brindisi, 72100
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Cremona, 26100
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Genova, 16132
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Livorno, 57123
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Meldola, 47014
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Milan, 20132
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Milan, 20133
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Milan, 20162
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Modena, 41124
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Naples, 80131
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Novara, 28100
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Orbassano, 10043
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Padova, 35128
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Pavia, 27100
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Pisa, 56126
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Pordenone, 33170
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Ravenna, 48121
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Rimini, 47900
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Roma, 00128
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Roma, 00152
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Rozzano, 20089
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Terni, 05100
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Torino, 10126
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Verona, 37134
Spain24 sites
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A Coruña, Galicia, 15006
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Badalona, Catalonia, 08916
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Barcelona, Catalonia, 08003
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Barcelona, Catalonia, 08023
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Barcelona, Catalonia, 08025
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Barcelona, Catalonia, 08035
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Barcelona, Catalonia, 08036
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Elche, Valencia, 03016
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L'Hospitalet de Llobregat, Catalonia, 08908
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Madrid, Madrid, Communidad de, 28007
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Madrid, Madrid, Communidad de, 28040
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Madrid, Madrid, Communidad de, 28041
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Madrid, Madrid, Communidad de, 28050
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Madrid, Madrid, Communidad de, 28922
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Majadahonda, Madrid, Communidad de, 28222
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Málaga, Andalusia, 29010
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Manresa, Catalonia, 08243
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Oviedo, Principality of Asturias, 33006
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Palma de Mallorca, Balearic Islands, 07010
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Pamplona, Navarre, 31008
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San Cristóbal de La Laguna, Canary Islands, 38320
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Santiago de Compostela, Galicia, 15706
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Seville, Andalusia, 41013
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Valencia, Valencia, 46009
France23 sites
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Angers, 49933
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Besançon, 25030
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Bordeaux, 33076
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Caen, 14076
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Clermont-Ferrand, 63011
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Dijon, 21079
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La Roche-sur-Yon, 85925
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Le Mans, 72000
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Lille, 59000
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Lyon, 69373
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Marseille, 13273
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Nancy, 54100
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Paris, 75005
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Paris, 75010
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Paris, 75014
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Paris, 75015
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Paris, 75230
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Pierre-Bénite, 69495
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Rennes, 35042
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Saint-Herblain, 44805
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Strasbourg, 67000
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Suresnes, 92151
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Villejuif, 94805
United Kingdom21 sites
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Aberdeen, AB25 2ZN
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Bath, BA1 3NG
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Birmingham, B15 2TH
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Brighton, BN2 5BE
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Bristol, BS2 8ED
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Cambridge, CB2 2QQ
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Cardiff, CF14 2TL
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Cottingham, HU16 5JQ
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Edinburgh, EH4 2XU
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Inverness, IV2 3UJ
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Lancaster, LA1 4RP
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Leeds, LS9 7TF
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London, SE1 9RT
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London, W12 0HS
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Maidstone, ME16 9QQ
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Metropolitan Borough of Wirral, CH63 4JY
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Northwood, HA6 2RN
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Plymouth, PL6 8DH
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Sheffield, S10 2SJ
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Southampton, S16 6YD
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Sutton, SM2 5PT
Australia18 sites
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Adelaide, South Australia, 5000
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Albury, New South Wales, 2640
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Bentleigh East, Victoria, 3165
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Box Hill, Victoria, 3128
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Concord, New South Wales, 2193
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Darlinghurst, New South Wales, 2010
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Hobart, Tasmania, 7000
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Kogarah, New South Wales, 2217
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Kurralta Park, South Australia, 5037
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Perth, Western Australia, 6000
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Port Macquarie, New South Wales, 2444
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Randwick, New South Wales, 2031
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South Brisbane, Queensland, 4101
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Southport, Queensland, 4215
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Wahroonga, New South Wales, 2076
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Westmead, New South Wales, 2145
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Wodonga, Victoria, 3690
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Woolloongabba, Queensland, 4102
Belgium10 sites
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Aalst, 9300
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Bonheiden, 2820
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Brussels, 1000
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Brussels, 1090
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Brussels, 1200
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Ghent, 9000
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Hasselt, 3500
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Leuven, B-3000
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Liège, 4000
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Roeselare, 8800
Netherlands10 sites
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Amsterdam, 1066 CX
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Groningen, 9713 GZ
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Groningen, 9728 NT
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Hoofddorp, 2134 TM
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Nieuwegein, 3435 CM
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Nijmegen, 6525 GA
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Rotterdam, 3045 PM
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Rotterdam, 3075 EA
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Tilburg, 5042 AD
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Zwolle, 8025 AB
Canada8 sites
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Calgary, Alberta, T2N 4N2
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Halifax, Nova Scotia, B3H 1V7
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London, Ontario, N6A 4L6
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Miramichi, New Brunswick, E1V 1Y3
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Montreal, Quebec, H2L4M1
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Owen Sound, Ontario, N4K 2J1
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Québec, G1R 2J6
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Vancouver, British Columbia, V5Z 4E6
Sweden7 sites
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Gotenborg, SE 41345
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Malmö, SE-20502
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Örebro, SE-70185
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Stockholm, SE-17176
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Umeå, SE-90184
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Uppsala, SE 75185
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Vaxjo, SE-35185
Austria4 sites
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Linz, 4010
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Salzburg, 5020
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Vienna, 1090
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Wein, 1100
Ireland4 sites
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Cork
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Dublin, 24
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Dublin, 7
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Galway
About this study
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
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.
- Being tested
- cabozantinib, prednisone
- Keywords
- prostate cancer, castration resistant prostate cancer, bone pain, CRPC
- Medical subject headings
- Prostatic Neoplasms, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cabozantinibDrug
Also called XL184
Tablets taken orally once-daily
prednisoneDrug
Taken twice a day orally. Commercially-obtained prednisone tablets will be over-encapsulated in order to blind identity.
| Study group | Role | What they receive |
|---|---|---|
| cabozantinib | Experimental | Subjects randomized to the cabozantinib arm will also receive placebo-matched prednisone capsules. Receives: Drug: cabozantinib |
| prednisone | Active comparator | Subjects randomized to the prednisone arm will also receive placebo-matched cabozantinib. Receives: Drug: prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
The primary analysis of OS is defined as the time from randomization to death due to any cause. Participants that had not died or were permanently lost to follow-up were censored at the last known date alive. Median OS was calculated using Kaplan-Meier estimates. Analysis for OS was performed after 614 events had occurred.
Measured: OS was measured from the time of randomization until 614 events, approximately 24 months after study start
Secondary outcomes (1)
Bone Scan Response (BSR)
BSR is defined as >=30% reduction in the bone scan lesion area (BSLA) compared with baseline. Confirmation of bone scan was not required for response or progression. Bone scans were evaluated by an independent radiology facility (IRF) for response.
Measured: BSR was measured at the end of Week 12 as determined by the IRF
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2012 (estimated)
- Study startJul 2012
- Primary completionSep 2014
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by ExelixisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,028 participants (actual)
Sponsor and investigators
- Lead sponsor
- Exelixis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01605227
- Sponsor's protocol ID
- XL184-307
- Other IDs
- 2012-001834-33
- Acronym
- COMET-1
- Status last verified
- Feb 2018
- First submitted
- 22 May 2012
- Last updated
- 14 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 29272162Smith 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.
PubMed 27400947