Study of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men With Previously Treated Symptomatic Castration-resistant Prostate Cancer (COMET-2)

This study is currently recruiting participants.
Verified January 2014 by Exelixis
Sponsor:
Information provided by (Responsible Party):
Exelixis
ClinicalTrials.gov Identifier:
NCT01522443
First received: January 13, 2012
Last updated: March 5, 2014
Last verified: January 2014
  Purpose

Bone metastases and associated pain are a major cause of morbidity and mortality in castration-resistant prostate cancer (CRPC). Most approved therapies have shown some ability to reduce soft tissue lesions but none meaningfully impacts bone metastases (as demonstrated by lack of resolution of lesions on bone scan with these agents) or the pain associated with these metastases.

This study will evaluate the effect of cabozantinib versus mitoxantrone plus prednisone on pain response and bone scan response in men with CRPC.


Condition Intervention Phase
Prostate Cancer
Castration Resistant Prostate Cancer
Pain
Prostatic Neoplasms
Drug: cabozantinib
Drug: mitoxantrone
Drug: prednisone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Controlled Trial of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men With Previously Treated Symptomatic Castration-resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Exelixis:

Primary Outcome Measures:
  • Confirmed pain response at Week 12 durable since Week 6 [ Time Frame: Week 6 and 12 ] [ Designated as safety issue: No ]
    Subjects will self-report information on pain and health-related quality of life via an interactive voice recognition system


Secondary Outcome Measures:
  • Bone scan response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Bone scans will be evaluated by an independent radiology facility for response

  • Overall survival [ Time Frame: through 28 months after study start ] [ Designated as safety issue: No ]

Estimated Enrollment: 246
Study Start Date: March 2012
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cabozantinib

Subjects randomized to the cabozantinib arm will also receive placebo mitoxantrone injections (color-matched with methylene blue) and placebo prednisone capsules.

There will be a maximum of 10 infusions for mitoxantrone placebo.

Drug: cabozantinib
Tablets taken orally once daily.
Active Comparator: Mitoxantrone/prednisone

Subjects randomized to the mitoxantrone + prednisone arm will also receive placebo cabozantinib tablets.

There will be a maximum of 10 infusions for mitoxantrone.

Drug: mitoxantrone
Given by IV once every 3 weeks.
Drug: prednisone
Taken twice a day orally by mouth. Commercially-obtained prednisone tablets will be over-encapsulated in order to blind identity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  • Documented pain from bone metastases that requires opioid narcotic intervention.
  • Adopted a narcotic regimen that consists of one sustained release opioid agent taken daily for chronic pain and one immediate release opioid agent for breakthrough pain.
  • Received prior docetaxel and either abiraterone or MDV3100 treatment and has evidence of investigator assessed 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.
  • A left-ventricular ejection fraction (LVEF) of >/= 50% assessed by echocardiogram or MUGA (multigated acquisition scan).
  • Capable of understanding and complying with the protocol requirements (including having the ability to access an interactive voice recognition system and self-report pain and narcotic use) 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 3 months after the last dose of study treatment.

Exclusion Criteria:

  • Prior treatment with cabozantinib or mitoxantrone.
  • 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 therapy in the last 4 weeks (includes radiation targeting bone metastases), radionuclide treatment in the last 6 weeks, or radiation therapy to the thoracic cavity (unless radiation targets bone metastases) in the past 3 months.
  • Treatment with serotonergic psychiatric medication(s) in the last 2 weeks (5 weeks for fluoxetine).
  • Known brain metastases or uncontrolled epidural disease.
  • Requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or FXa (coagulation factor X) inhibitors, or antiplatelet agents (eg, clopidogrel). Low dose aspirin (above low dose levels for cardioprotection per local applicable guidelines), low-dose warfarin (≤ 1 mg/day), and prophylactic low molecular weight heparin are permitted.
  • 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 of > 0.5 teaspoon of red blood, 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.
  • Corrected QT interval (QTc) > 500 ms in the last 4 weeks.
  • Unable to swallow capsules or tablets or tolerate infusions.
  • Previously-identified allergy or hypersensitivity to components of the study treatment formulations investigator or designee.
  • History of another malignancy (except non-melanoma skin cancer, adequately treated stage I colon cancer, superficial transitional carcinoma of the bladder) in the past 2 years.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01522443

Contacts
Contact: Exelixis Clinical Trials 1-888-393-5494
Contact: Backup or International +1-650-837-7400

  Hide Study Locations
Locations
United States, Arizona
Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Sherril Bierman    (480) 860-5000    sbierman@azpoh.com   
United States, California
Recruiting
La Jolla, California, United States, 92093
Contact: Arlene Araneta    858-822-5374    aaraneta@ucsd.edu   
Withdrawn
Los Angeles, California, United States, 90024
Recruiting
Los Angeles, California, United States, 90073
Contact: Sherry Jeffrey    (310) 268-3670    sheryl.jeffery@va.gov   
Recruiting
Marina del Rey, California, United States, 90292
Contact: Jennifer Leung    310 827 7707 ext 32      
Recruiting
San Diego, California, United States, 92123
Contact: Cathy Wood    858-939-5062    cathy.wood@sharp.com   
Recruiting
San Francisco, California, United States, 94115
Contact: Joni Beemsterber    415-600-3967    beemstj@cpmcri.org   
Recruiting
Santa Barbara, California, United States, 93105
Contact: Erika Wheeler    (805) 898-2192    ewheeler@ccsb.org   
Recruiting
Stanford, California, United States, 94305
Contact: Denise Haas    670.736.1251    dhaas@stanford.edu   
United States, Colorado
Recruiting
Aurora, Colorado, United States, 80012
Contact: Karen Morris    303-418-7639    Karen.Morris@usoncology.com   
Recruiting
Littleton, Colorado, United States, 80122
Contact: Pamela Eichler    303-765-3537    pamelaeichler@centura.org   
United States, District of Columbia
Recruiting
Washington, District of Columbia, United States, 20037
Contact: Hiwot Guebre-Xabiher    202-741-2981    hguebrexabiher@mfa.gwu.edu   
United States, Florida
Active, not recruiting
Boca Raton, Florida, United States, 33486
United States, Georgia
Recruiting
Athens, Georgia, United States, 30607
Contact: Jamie Hodgson       jhodgson@universitycancer.com   
United States, Illinois
Recruiting
Chicago, Illinois, United States, 60611
Contact: Timothy Kuzel    312.695.1384    t-kuzel@northwestern.edu   
United States, Indiana
Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Kristen Catron    (317) 278-4840    klshirar@indiana.edu   
United States, Iowa
Recruiting
Iowa City, Iowa, United States, 52242
Contact: Daniel Vaena    319- 38-0581    daniel.vaena@uiowa.edu   
United States, Kansas
Recruiting
Westwood, Kansas, United States, 66025
Contact: Jodi Carlson    913-945-7552    jcarlson@kumc.edu   
United States, Kentucky
Recruiting
Louisville, Kentucky, United States, 40202
Contact: Pamela Adkisson    502-629-5315    pamela.adkisson@nortonhealthcare.org   
United States, Louisiana
Active, not recruiting
New Orleans, Louisiana, United States, 70112
United States, Maryland
Recruiting
Baltimore, Maryland, United States, 21231
Contact: Emmanuel Antonarakis, MD    443-297-0553    eantona1@jhmi.edu   
Contact: Avery Spitz    410-502-2043    aspitz2@jhmi.edu   
United States, Michigan
Recruiting
Detroit, Michigan, United States, 48202
Contact: Constance Harkness, MD    313-916-1048    charkne1@hfhs.org   
Recruiting
Detroit, Michigan, United States, 48201
Contact: Nimrit Sohal    313 576-9386    sohaln@karmanos.org   
United States, Minnesota
Not yet recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Debra Herzan    (612) 626-4495    herza001@umn.edu   
United States, Mississippi
Recruiting
Tupelo, Mississippi, United States, 38801
Contact: Marthe Thomas    662.407.4090    mthomas_nmho@dixie-net.com   
United States, Missouri
Recruiting
St. Louis, Missouri, United States, 63110
Contact: Chris Grant    314-747-3575    cgrant@dom.wustl.edu   
United States, Nebraska
Recruiting
Omaha, Nebraska, United States, 68198
Contact: Terry Burke    402-559-8649    tburke@unmc.edu   
United States, Nevada
Recruiting
Las Vegas, Nevada, United States, 89109
Contact: David Anderson    702-952-3400    David.Anderson@usoncology.com   
United States, New Jersey
Recruiting
New Brunswick, New Jersey, United States
Contact: Mark Stein    732-235-5773    steinmn@umdnj.edu   
United States, New York
Recruiting
Buffalo, New York, United States, 14263
Contact: Saby George, MD    1-877-275-7724    AskRPCI@roswellpark.org   
Recruiting
New York, New York, United States, 10065
Contact: Brieyona Reaves    646-227-2173    reavesb@mskcc.org   
Recruiting
New York, New York, United States, 10019
Contact: Tahir Mirzoyed    (212) 523-7289    TMirzoye@chpnet.org   
Recruiting
New York, New York, United States, 10022
Contact: Dahlia Norry    646-227-2154    norryd@mskcc.org   
United States, North Carolina
Recruiting
Chapel Hill, North Carolina, United States, 27516
Contact: Gayle Grigson    (919) 966-4432    gayle_grigson@med.unc.edu   
Recruiting
Durham, North Carolina, United States, 27710
Contact: Peggy Lyons    919-668-0413    peggy.lyons@duke.edu   
Active, not recruiting
Raleigh, North Carolina, United States, 27607
United States, Ohio
Recruiting
Cleveland, Ohio, United States, 44195
Contact: Robert Dreicer    216-445-4623    dreicer@ccf.org   
United States, Oklahoma
Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Alicia Hancock    405-271-8001 ext 53482    alisha-hancock@ouhsc.edu   
United States, Pennsylvania
Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Diana Long    412-647-8475    longdl@upmc.edu   
United States, South Dakota
Recruiting
Watertown, South Dakota, United States, 57201
Contact: Lisa Campbell    605-882-6800    lisa.campbell@prairielakes.com   
United States, Tennessee
Recruiting
Memphis, Tennessee, United States, 38120
Contact: Bradley Somer    901-683-0055    bsomer@westclinic.com   
Active, not recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Recruiting
Dallas, Texas, United States, 75246
Contact: Rita Lopez    214-370-1846    rita.lopez2@usoncology.com   
Active, not recruiting
Round Rock, Texas, United States, 78681
United States, Utah
Not yet recruiting
Salt Lake City, Utah, United States, 84112
Contact: Sally Fairgbairn    (801) 587-4765    sally.fairbairn@hci.utah.edu   
United States, Virginia
Recruiting
Norfolk, Virginia, United States, 23502
Contact: Wendi Gobhardt       wendi.gobhardt@usoncology.com   
United States, Washington
Recruiting
Seattle, Washington, United States, 98104
Contact: Barry Boatman    206-215-3086    CancerResearch@swedish.org   
United States, Wisconsin
Recruiting
Madison, Wisconsin, United States, 53705
Contact: Cancer Connect    800-622-8922    cancerconnect@uwcarbone.wisc.edu   
Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Rebecca Selle    414-805-8748    rselle@mcw.edu   
Australia, New South Wales
Recruiting
Concord, New South Wales, Australia, 2139
Contact: Kath Hall    +61 2 9767 7576      
Recruiting
Darlinghurst, New South Wales, Australia, 2010
Contact: Sandra Montez    +612 9355 5614    smontez@stvincents.com.au   
Recruiting
Kogarah, New South Wales, Australia, 2217
Contact: Julie Ward    +61 2 9598 5310    WardJu@ramsayhealth.com.au   
Recruiting
Port Macquarie, New South Wales, Australia, 2444
Contact: Pip Williams    +61 2 6580 1818    pip.williams@ncahs.health.nsw.gov.au   
Recruiting
Randwick, New South Wales, Australia, 2031
Contact: Heather Kilsby    +61 2 9382 2959    heather.kilsby@sesiahs.health.nsw.gov.au   
Not yet recruiting
Wahroonga, New South Wales, Australia, 2076
Contact: Nitin Bansal    61294804352    nitin.bansal@sah.org.au   
Australia, Queensland
Recruiting
Milton, Queensland, Australia, 4064
Recruiting
South Brisbane, Queensland, Australia, 4101
Contact: Trang Le    617 3737 4759    tle@hoca.com.au   
Recruiting
Woolloongabba, Queensland, Australia, 4102
Contact: Jen Suffolk    +61 7 3176 7825    jennifer_m_suffolk@health.qld.gov.au   
Australia, Victoria
Recruiting
Box Hill, Victoria, Australia, 3128
Contact: Amanda Pereira    +61 3 9095 2466    amanda.pereira@easternhealth.org.au   
Not yet recruiting
Wodonga, Victoria, Australia, 3690
Australia, Western Australia
Recruiting
Subiaco, Western Australia, Australia
Canada, British Columbia
Recruiting
Kelowna, British Columbia, Canada, V1Y 5L3
Contact: Jeaneen Rudolph    (250) 712-3966 ext 686811    jrudolph@bccancer.bc.ca   
Recruiting
Vancouver, British Columbia, Canada, V57 4E6
Contact: Kim Chi    604-817-6000 ext 2746    kchi@bccancer.bc.ca   
Canada, Ontario
Recruiting
London, Ontario, Canada, N6A 4L6
Contact: Eric Winquist    (519) 685-8600    eric.winquist@lhsc.on.ca   
Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Urban Emmeneggar, MD    416-480-4928    urban.emmenegger@sunnybrook.ca   
Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Ian Tannock, MD, PhD, DSc    416 946 2245    Ian.Tannock@uhn.ca   
Ireland
Not yet recruiting
Dublin, Ireland, 7
Not yet recruiting
Dublin, Ireland, 24
United Kingdom
Not yet recruiting
Bath, England, United Kingdom, BA1 3NG
Contact: Mark Beresford    01225 824797      
Not yet recruiting
Cambridge, England, United Kingdom, CB2 0QQ
Contact: Cambridge Cancer Trials Center    +44(0)1223 216083    cctc@addenbrookes.nhs.uk   
Not yet recruiting
Leeds, England, United Kingdom, LS9 7TF
Contact: Satinder Jagdev    +44(0)1132067935      
Not yet recruiting
London, England, United Kingdom, W12 0HS
Contact: Maria Martinez    +44 (0)208 383 3089    maria.martinez@imperial.nhs.uk   
Recruiting
London, England, United Kingdom, SE1 9RT
Contact: Hazel Harrop    2071882007    Urologyresearchteam@gstt.nhs.uk   
Not yet recruiting
London, England, United Kingdom, NW1 2PG
Contact: Anneliese Gillesen    +44 (0)203 447 4698      
Recruiting
Manchester, England, United Kingdom, M20 4BX
Contact: Joanne Oliver    +44 (0)161 4468043    joanne.oliver@christie.nhs.uk   
Not yet recruiting
Rickmansworth, England, United Kingdom, HA6 2RN
Contact: Peter Hoskin       peter.hoskin@nhs.net   
Not yet recruiting
Slough, England, United Kingdom, SL2 4HL
Recruiting
Sutton, England, United Kingdom, SM2 5PT
Contact: Diletta Bianchini    +44 (0) 208 6426011 ext 1393    Diletta.Bianchini@icr.ac.uk   
Recruiting
Wirral, England, United Kingdom, CH63 4JY
Contact: Alison Hassal    +44 (0)151 334 1155 ext 4097    alison.hassall@clatterbridgecc.nhs.uk   
Recruiting
Aberdeen, Scotland, United Kingdom, AB25 2ZN
Contact: Sue Rodwell    +44 1224 553830    s.rodwell@nhs.net   
Recruiting
Edinburgh, Scotland, United Kingdom, EH4 2XU
Contact: Lisa Egan    +44 0131 537 3269      
Recruiting
Glasgow, Scotland, United Kingdom, G12 0YN
Contact: Hilary Glen    0141 301 7121    hilary.glen@ggc.scot.nhs.uk   
Not yet recruiting
Inverness, Scotland, United Kingdom, RO17
Contact: Cancer Clinical Trials Office    +44 (0)1463 706264      
Recruiting
Belfast, United Kingdom
Contact: Joe O'Sullivan    +44(0) 28 95048549    joe.osullivan@qub.ac.uk   
Sponsors and Collaborators
Exelixis
  More Information

No publications provided

Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT01522443     History of Changes
Other Study ID Numbers: XL184-306
Study First Received: January 13, 2012
Last Updated: March 5, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Exelixis:
prostate cancer
castration resistant prostate cancer
bone pain
CRPC

Additional relevant MeSH terms:
Neoplasms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Mitoxantrone
Prednisone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 17, 2014