Study of Cabozantinib (XL184) Versus Prednisone in Men With Metastatic Castration-resistant Prostate Cancer Previously Treated With Docetaxel and Abiraterone or MDV3100
COMET-1
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
2 other identifiers
interventional
1,028
13 countries
246
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 prostate-cancer
Started Jul 2012
Shorter than P25 for phase_3 prostate-cancer
246 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 22, 2012
CompletedFirst Posted
Study publicly available on registry
May 24, 2012
CompletedStudy Start
First participant enrolled
July 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2015
CompletedResults Posted
Study results publicly available
March 14, 2018
CompletedMarch 14, 2018
February 1, 2018
2.2 years
May 22, 2012
May 23, 2017
February 14, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
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 was measured at the end of Week 12 as determined by the IRF
Other Outcomes (1)
Progression-free Survival (PFS)
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
Study Arms (2)
cabozantinib
EXPERIMENTALSubjects randomized to the cabozantinib arm will also receive placebo-matched prednisone capsules.
prednisone
ACTIVE COMPARATORSubjects randomized to the prednisone arm will also receive placebo-matched cabozantinib.
Interventions
Taken twice a day orally. Commercially-obtained prednisone tablets will be over-encapsulated in order to blind identity.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Exelixislead
Study Sites (264)
Unknown Facility
Birmingham, Alabama, 35205, United States
Unknown Facility
Anchorage, Alaska, 99508, United States
Unknown Facility
Phoenix, Arizona, 85016, United States
Unknown Facility
Scottsdale, Arizona, 85255, United States
Unknown Facility
Tucson, Arizona, 85710, United States
Unknown Facility
Jonesboro, Arkansas, 72401, United States
Unknown Facility
Duarte, California, 91010, United States
Unknown Facility
Highland, California, 92346, United States
Unknown Facility
La Jolla, California, 92093, United States
Unknown Facility
Los Angeles, California, 90033, United States
Unknown Facility
Montebello, California, 90640, United States
Unknown Facility
Orange, California, 92868, United States
Unknown Facility
Palo Alto, California, 94301, United States
Unknown Facility
Rancho Mirage, California, 92270, United States
Unknown Facility
San Marcos, California, 92069, United States
Unknown Facility
St. Helena, California, 94574, United States
Unknown Facility
Vallejo, California, 94589, United States
Unknown Facility
Aurora, Colorado, 80045, United States
Unknown Facility
New Haven, Connecticut, 06520, United States
Unknown Facility
Southington, Connecticut, 06489, United States
Unknown Facility
Miami Beach, Florida, 33140, United States
Unknown Facility
Ocala, Florida, 34471, United States
Unknown Facility
Orlando, Florida, 32806, United States
Unknown Facility
Tampa, Florida, 33612, United States
Unknown Facility
Titusville, Florida, 32796, United States
Unknown Facility
Wellington, Florida, 33449, United States
Unknown Facility
West Palm Beach, Florida, 33401, United States
Unknown Facility
Athens, Georgia, 30607, United States
Unknown Facility
Atlanta, Georgia, 30318, United States
Unknown Facility
Marietta, Georgia, 30060, United States
Unknown Facility
Galesburg, Illinois, 61401, United States
Unknown Facility
Niles, Illinois, 60714, United States
Unknown Facility
Ames, Iowa, 50010, United States
Unknown Facility
Sioux City, Iowa, 51101, United States
Unknown Facility
Wichita, Kansas, 67214, United States
Unknown Facility
Hazard, Kentucky, 41701, United States
Unknown Facility
Louisville, Kentucky, 40202, United States
Unknown Facility
Brewer, Maine, 04412, United States
Unknown Facility
Baltimore, Maryland, 21201, United States
Unknown Facility
Bethesda, Maryland, 20817, United States
Unknown Facility
Towson, Maryland, 21204, United States
Unknown Facility
Boston, Massachusetts, 02114, United States
Unknown Facility
Boston, Massachusetts, 02118, United States
Unknown Facility
Methuen, Massachusetts, 01844, United States
Unknown Facility
Detroit, Michigan, 48202, United States
Unknown Facility
Wyoming, Michigan, 49509, United States
Unknown Facility
Minneapolis, Minnesota, 55455, United States
Unknown Facility
Jefferson City, Missouri, 65109, United States
Unknown Facility
Springfield, Missouri, 65804, United States
Unknown Facility
Lincoln, Nebraska, 68506, United States
Unknown Facility
Omaha, Nebraska, 68130, United States
Unknown Facility
Hackensack, New Jersey, 07601, United States
Unknown Facility
Lawrenceville, New Jersey, 08648, United States
Unknown Facility
Albany, New York, 12208, United States
Unknown Facility
Garden City, New York, 11530, United States
Unknown Facility
New York, New York, 10065, United States
Unknown Facility
Pinehurst, North Carolina, 28374, United States
Unknown Facility
Bismarck, North Dakota, 58501, United States
Unknown Facility
Cincinnati, Ohio, 45219, United States
Unknown Facility
Columbus, Ohio, 43221, United States
Unknown Facility
Portland, Oregon, 97227, United States
Unknown Facility
Bryn Mawr, Pennsylvania, 19010, United States
Unknown Facility
Hershey, Pennsylvania, 17033, United States
Unknown Facility
Lancaster, Pennsylvania, 17604, United States
Unknown Facility
Greenville, South Carolina, 29615, United States
Unknown Facility
Chattanooga, Tennessee, 37421, United States
Unknown Facility
Amarillo, Texas, 79106, United States
Unknown Facility
Bedford, Texas, 76022, United States
Unknown Facility
Houston, Texas, 77024, United States
Unknown Facility
Laredo, Texas, 78041, United States
Unknown Facility
San Antonio, Texas, 78217, United States
Unknown Facility
Salt Lake City, Utah, 84112, United States
Unknown Facility
Burlington, Vermont, 05405, United States
Unknown Facility
Fairfax, Virginia, 22031, United States
Unknown Facility
Newport News, Virginia, 23601, United States
Unknown Facility
Spokane, Washington, 99204, United States
Unknown Facility
Green Bay, Wisconsin, 54311, United States
Unknown Facility
Albury, New South Wales, 2640, Australia
Unknown Facility
Concord, New South Wales, 2193, Australia
Unknown Facility
Darlinghurst, New South Wales, 2010, Australia
Unknown Facility
Kogarah, New South Wales, 2217, Australia
Unknown Facility
Port Macquarie, New South Wales, 2444, Australia
Unknown Facility
Randwick, New South Wales, 2031, Australia
Unknown Facility
Wahroonga, New South Wales, 2076, Australia
Unknown Facility
Westmead, New South Wales, 2145, Australia
Unknown Facility
South Brisbane, Queensland, 4101, Australia
Unknown Facility
Southport, Queensland, 4215, Australia
Unknown Facility
Woolloongabba, Queensland, 4102, Australia
Unknown Facility
Adelaide, South Australia, 5000, Australia
Unknown Facility
Kurralta Park, South Australia, 5037, Australia
Unknown Facility
Hobart, Tasmania, 7000, Australia
Unknown Facility
Bentleigh East, Victoria, 3165, Australia
Unknown Facility
Box Hill, Victoria, 3128, Australia
Unknown Facility
Wodonga, Victoria, 3690, Australia
Unknown Facility
Perth, Western Australia, 6000, Australia
Unknown Facility
Linz, 4010, Austria
Unknown Facility
Salzburg, 5020, Austria
Unknown Facility
Vienna, 1090, Austria
Unknown Facility
Wein, 1100, Austria
Unknown Facility
Aalst, 9300, Belgium
Unknown Facility
Bonheiden, 2820, Belgium
Unknown Facility
Brussels, 1000, Belgium
Unknown Facility
Brussels, 1090, Belgium
Unknown Facility
Brussels, 1200, Belgium
Unknown Facility
Ghent, 9000, Belgium
Unknown Facility
Hasselt, 3500, Belgium
Unknown Facility
Leuven, B-3000, Belgium
Unknown Facility
Liège, 4000, Belgium
Unknown Facility
Roeselare, 8800, Belgium
Unknown Facility
Calgary, Alberta, T2N 4N2, Canada
Unknown Facility
Vancouver, British Columbia, V5Z 4E6, Canada
Unknown Facility
Miramichi, New Brunswick, E1V 1Y3, Canada
Unknown Facility
Halifax, Nova Scotia, B3H 1V7, Canada
Unknown Facility
London, Ontario, N6A 4L6, Canada
Unknown Facility
Owen Sound, Ontario, N4K 2J1, Canada
Unknown Facility
Montreal, Quebec, H2L4M1, Canada
Unknown Facility
Québec, G1R 2J6, Canada
Unknown Facility
Angers, 49933, France
Unknown Facility
Besançon, 25030, France
Unknown Facility
Bordeaux, 33076, France
Unknown Facility
Caen, 14076, France
Unknown Facility
Clermont-Ferrand, 63011, France
Unknown Facility
Dijon, 21079, France
Unknown Facility
La Roche-sur-Yon, 85925, France
Unknown Facility
Le Mans, 72000, France
Unknown Facility
Lille, 59000, France
Unknown Facility
Lyon, 69373, France
Unknown Facility
Marseille, 13273, France
Unknown Facility
Nancy, 54100, France
Unknown Facility
Paris, 75005, France
Unknown Facility
Paris, 75010, France
Unknown Facility
Paris, 75014, France
Unknown Facility
Paris, 75015, France
Unknown Facility
Paris, 75230, France
Unknown Facility
Pierre-Bénite, 69495, France
Unknown Facility
Rennes, 35042, France
Unknown Facility
Saint-Herblain, 44805, France
Unknown Facility
Strasbourg, 67000, France
Unknown Facility
Suresnes, 92151, France
Unknown Facility
Villejuif, 94805, France
Unknown Facility
Aachen, 52062, Germany
Unknown Facility
Aachen, 52074, Germany
Unknown Facility
Berlin, 12200, Germany
Unknown Facility
Berlin, 13055, Germany
Unknown Facility
Braunschweig, 38126, Germany
Unknown Facility
Cologne, 50968, Germany
Unknown Facility
Dresden, 01307, Germany
Unknown Facility
Düsseldorf, 40225, Germany
Unknown Facility
Frankfurt am Main, 60488, Germany
Unknown Facility
Freiburg im Breisgau, 79106, Germany
Unknown Facility
Fürth, 90766, Germany
Unknown Facility
Gütersloh, 33332, Germany
Unknown Facility
Hamburg, 20246, Germany
Unknown Facility
Hamburg, 22399, Germany
Unknown Facility
Hamburg, 22763, Germany
Unknown Facility
Hanover, 30625, Germany
Unknown Facility
Heidelberg, 69120, Germany
Unknown Facility
Homburg, 66421, Germany
Unknown Facility
Kassel, 34125, Germany
Unknown Facility
Kempen, 47906, Germany
Unknown Facility
Kirchheim, 73230, Germany
Unknown Facility
Mannheim, 68167, Germany
Unknown Facility
München, 81675, Germany
Unknown Facility
Münster, 48149, Germany
Unknown Facility
Nürtingen, 72622, Germany
Unknown Facility
Offenburg, 77654, Germany
Unknown Facility
Traunstein, 83278, Germany
Unknown Facility
Tübingen, 72076, Germany
Unknown Facility
Weiden, 92637, Germany
Unknown Facility
Wuppertal, 42103, Germany
Unknown Facility
Cork, Ireland
Unknown Facility
Dublin, 24, Ireland
Unknown Facility
Dublin, 7, Ireland
Unknown Facility
Galway, Ireland
Unknown Facility
Ancona, 60126, Italy
Unknown Facility
Arezzo, 52100, Italy
Unknown Facility
Aviano, 33081, Italy
Unknown Facility
Brindisi, 72100, Italy
Unknown Facility
Cremona, 26100, Italy
Unknown Facility
Genova, 16132, Italy
Unknown Facility
Livorno, 57123, Italy
Unknown Facility
Meldola, 47014, Italy
Unknown Facility
Milan, 20132, Italy
Unknown Facility
Milan, 20133, Italy
Unknown Facility
Milan, 20162, Italy
Unknown Facility
Modena, 41124, Italy
Unknown Facility
Napoli, 80131, Italy
Unknown Facility
Novara, 28100, Italy
Unknown Facility
Orbassano, 10043, Italy
Unknown Facility
Padua, 35128, Italy
Unknown Facility
Pavia, 27100, Italy
Unknown Facility
Pisa, 56126, Italy
Unknown Facility
Pordenone, 33170, Italy
Unknown Facility
Ravenna, 48121, Italy
Unknown Facility
Rimini, 47900, Italy
Unknown Facility
Roma, 00128, Italy
Unknown Facility
Roma, 00152, Italy
Unknown Facility
Rozzano, 20089, Italy
Unknown Facility
Terni, 05100, Italy
Unknown Facility
Torino, 10126, Italy
Unknown Facility
Verona, 37134, Italy
Unknown Facility
Amsterdam, 1066 CX, Netherlands
Unknown Facility
Groningen, 9713 GZ, Netherlands
Unknown Facility
Groningen, 9728 NT, Netherlands
Unknown Facility
Hoofddorp, 2134 TM, Netherlands
Unknown Facility
Nieuwegein, 3435 CM, Netherlands
Unknown Facility
Nijmegen, 6525 GA, Netherlands
Unknown Facility
Rotterdam, 3045 PM, Netherlands
Unknown Facility
Rotterdam, 3075 EA, Netherlands
Unknown Facility
Tilburg, 5042 AD, Netherlands
Unknown Facility
Zwolle, 8025 AB, Netherlands
Unknown Facility
Ponce, 00716, Puerto Rico
Unknown Facility
Málaga, Andalusia, 29010, Spain
Unknown Facility
Seville, Andalusia, 41013, Spain
Unknown Facility
Palma de Mallorca, Balearic Islands, 07010, Spain
Unknown Facility
San Cristóbal de La Laguna, Canary Islands, 38320, Spain
Unknown Facility
Badalona, Catalonia, 08916, Spain
Unknown Facility
Barcelona, Catalonia, 08003, Spain
Unknown Facility
Barcelona, Catalonia, 08023, Spain
Unknown Facility
Barcelona, Catalonia, 08025, Spain
Unknown Facility
Barcelona, Catalonia, 08035, Spain
Unknown Facility
Barcelona, Catalonia, 08036, Spain
Unknown Facility
L'Hospitalet de Llobregat, Catalonia, 08908, Spain
Unknown Facility
Manresa, Catalonia, 08243, Spain
Unknown Facility
A Coruña, Galicia, 15006, Spain
Unknown Facility
Santiago de Compostela, Galicia, 15706, Spain
Unknown Facility
Madrid, Madrid, Communidad de, 28007, Spain
Unknown Facility
Madrid, Madrid, Communidad de, 28040, Spain
Unknown Facility
Madrid, Madrid, Communidad de, 28041, Spain
Unknown Facility
Madrid, Madrid, Communidad de, 28050, Spain
Unknown Facility
Madrid, Madrid, Communidad de, 28922, Spain
Unknown Facility
Majadahonda, Madrid, Communidad de, 28222, Spain
Unknown Facility
Pamplona, Navarre, 31008, Spain
Unknown Facility
Oviedo, Principality of Asturias, 33006, Spain
Unknown Facility
Elche, Valencia, 03016, Spain
Unknown Facility
Valencia, Valencia, 46009, Spain
Unknown Facility
Gotenborg, SE 41345, Sweden
Unknown Facility
Malmo, SE-20502, Sweden
Unknown Facility
Örebro, SE-70185, Sweden
Unknown Facility
Stockholm, SE-17176, Sweden
Unknown Facility
Umeå, SE-90184, Sweden
Unknown Facility
Uppsala, SE 75185, Sweden
Unknown Facility
Vaxjo, SE-35185, Sweden
Unknown Facility
Aberdeen, AB25 2ZN, United Kingdom
Unknown Facility
Bath, BA1 3NG, United Kingdom
Unknown Facility
Birmingham, B15 2TH, United Kingdom
Unknown Facility
Brighton, BN2 5BE, United Kingdom
Unknown Facility
Bristol, BS2 8ED, United Kingdom
Unknown Facility
Cambridge, CB2 2QQ, United Kingdom
Unknown Facility
Cardiff, CF14 2TL, United Kingdom
Unknown Facility
Cottingham, HU16 5JQ, United Kingdom
Unknown Facility
Edinburgh, EH4 2XU, United Kingdom
Unknown Facility
Inverness, IV2 3UJ, United Kingdom
Unknown Facility
Lancaster, LA1 4RP, United Kingdom
Unknown Facility
Leeds, LS9 7TF, United Kingdom
Unknown Facility
London, SE1 9RT, United Kingdom
Unknown Facility
London, W12 0HS, United Kingdom
Unknown Facility
Maidstone, ME16 9QQ, United Kingdom
Unknown Facility
Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
Unknown Facility
Northwood, HA6 2RN, United Kingdom
Unknown Facility
Plymouth, PL6 8DH, United Kingdom
Unknown Facility
Sheffield, S10 2SJ, United Kingdom
Unknown Facility
Southampton, S16 6YD, United Kingdom
Unknown Facility
Sutton, SM2 5PT, United Kingdom
Related Publications (2)
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.
PMID: 29272162DERIVEDSmith 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.
PMID: 27400947DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Exelixis Medical Information
- Organization
- Exelixis, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 22, 2012
First Posted
May 24, 2012
Study Start
July 1, 2012
Primary Completion
September 1, 2014
Study Completion
March 1, 2015
Last Updated
March 14, 2018
Results First Posted
March 14, 2018
Record last verified: 2018-02