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. (see Contacts and Locations)
Verified June 2014 by Exelixis
Information provided by (Responsible Party):
Exelixis Identifier:
First received: January 13, 2012
Last updated: June 13, 2014
Last verified: June 2014

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
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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01522443

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

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United States, Arizona
Active, not recruiting
Scottsdale, Arizona, United States, 85258
United States, California
La Jolla, California, United States, 92093
Contact: Arlene Araneta    858-822-5374   
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Los Angeles, California, United States, 90024
Los Angeles, California, United States, 90073
Contact: Sherry Jeffrey    (310) 268-3670   
Marina del Rey, California, United States, 90292
Contact: Jennifer Leung    310 827 7707 ext 32      
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Contact: Cathy Wood    858-939-5062   
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Aurora, Colorado, United States, 80012
Contact: Karen Morris    303-418-7639   
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Boca Raton, Florida, United States, 33486
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Athens, Georgia, United States, 30607
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Chicago, Illinois, United States, 60611
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Indianapolis, Indiana, United States, 46202
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Iowa City, Iowa, United States, 52242
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Westwood, Kansas, United States, 66025
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Louisville, Kentucky, United States, 40202
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New Orleans, Louisiana, United States, 70112
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Baltimore, Maryland, United States, 21231
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Contact: Avery Spitz    410-502-2043   
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Detroit, Michigan, United States, 48202
Contact: Constance Harkness, MD    313-916-1048   
Detroit, Michigan, United States, 48201
Contact: Nimrit Sohal    313 576-9386   
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Minneapolis, Minnesota, United States, 55455
Contact: Debra Herzan    (612) 626-4495   
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Tupelo, Mississippi, United States, 38801
Contact: Marthe Thomas    662.407.4090   
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Omaha, Nebraska, United States, 68198
Contact: Terry Burke    402-559-8649   
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Las Vegas, Nevada, United States, 89109
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New Brunswick, New Jersey, United States
Contact: Mark Stein    732-235-5773   
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Buffalo, New York, United States, 14263
Contact: Saby George, MD    1-877-275-7724   
New York, New York, United States, 10065
Contact: Brieyona Reaves    646-227-2173   
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Contact: Tahir Mirzoyed    (212) 523-7289   
New York, New York, United States, 10022
Contact: Dahlia Norry    646-227-2154   
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Chapel Hill, North Carolina, United States, 27516
Contact: Gayle Grigson    (919) 966-4432   
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Contact: Peggy Lyons    919-668-0413   
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Cleveland, Ohio, United States, 44195
Contact: Robert Dreicer    216-445-4623   
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Oklahoma City, Oklahoma, United States, 73104
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Pittsburgh, Pennsylvania, United States, 15232
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Watertown, South Dakota, United States, 57201
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Memphis, Tennessee, United States, 38120
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Seattle, Washington, United States, 98104
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Madison, Wisconsin, United States, 53705
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Concord, New South Wales, Australia, 2139
Contact: Kath Hall    +61 2 9767 7576      
Darlinghurst, New South Wales, Australia, 2010
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Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: Exelixis Identifier: NCT01522443     History of Changes
Other Study ID Numbers: XL184-306
Study First Received: January 13, 2012
Last Updated: June 13, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
Ireland: Irish Medicines Board

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

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal processed this record on August 19, 2014