Trial record 1 of 1 for:    NCT01522443
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Study of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men With Previously Treated Symptomatic Castration-resistant Prostate Cancer (COMET-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01522443
Recruitment Status : Terminated (Stopped after the outcome of cabozantinib Phase 3 CRPC study XL184-307.)
First Posted : January 31, 2012
Results First Posted : May 23, 2018
Last Update Posted : May 23, 2018
Information provided by (Responsible Party):

Brief Summary:

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 or disease Intervention/treatment Phase
Prostate Cancer Castration Resistant Prostate Cancer Pain Prostatic Neoplasms Drug: cabozantinib Drug: mitoxantrone Drug: prednisone Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 119 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : March 2012
Actual Primary Completion Date : October 2014
Actual Study Completion Date : January 13, 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Pain Response at Week 6 Confirmed at Week 12, Week 12 Reported [ Time Frame: Pain response was measured at Week 6 and Week 12 by self-reports of subjects ]
    The pre-specified primary analysis of Pain Response at Week 6 confirmed at Week 12 was defined as ≥ 30% from baseline in the average daily worst pain intensity score during a 7-day reporting period, with neither a concomitant increase in average daily use of any opioid narcotic type, nor addition of any new opioid narcotic type, relative to baseline. Pain Progression at a given time point is defined as ≥ 30% increase compared with baseline in the average daily worst pain intensity score during a 7-day reporting period or either an increase in the average daily use of any type of opioid narcotic or addition of a new opioid narcotic type compared with baseline.

Secondary Outcome Measures :
  1. Bone Scan Response (BSR) [ Time Frame: BSR was measured at the end of Week 12 as determined by the IRF ]
    BSR is defined as >=30% in the bone scan lesion area (BSLA) compared with baseline. Bones scans were evaluated by an independent radiology facility (IRF) for response.

  2. Overall Survival (OS) [ Time Frame: OS was measured at the time of randomization until 78 deaths ]
    OS was defined as the time from randomization to the date of death (due to any cause). Participants that had not died were censored at last known date alive. The analyses for OS occurred after 78/196 deaths (40% of the total required for the pre-specified primary analysis of OS). The data cut-off date was 06 October 2014. Median OS was calculated using Kaplan-Meier estimates.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01522443

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United States, Arizona
Scottsdale, Arizona, United States, 85258
United States, California
La Jolla, California, United States, 92093
Los Angeles, California, United States, 90024
Los Angeles, California, United States, 90073
Marina Del Rey, California, United States, 90292
San Diego, California, United States, 92123
San Francisco, California, United States, 94115
Santa Barbara, California, United States, 93105
Stanford, California, United States, 94305
United States, Colorado
Aurora, Colorado, United States, 80012
Littleton, Colorado, United States, 80122
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Washington, District of Columbia, United States, 20037
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Boca Raton, Florida, United States, 33486
United States, Georgia
Athens, Georgia, United States, 30607
United States, Illinois
Chicago, Illinois, United States, 60611
United States, Indiana
Indianapolis, Indiana, United States, 46202
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Iowa City, Iowa, United States, 52242
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Westwood, Kansas, United States, 66025
United States, Kentucky
Louisville, Kentucky, United States, 40202
United States, Louisiana
New Orleans, Louisiana, United States, 70112
United States, Maryland
Baltimore, Maryland, United States, 21231
United States, Michigan
Detroit, Michigan, United States, 48201
Detroit, Michigan, United States, 48202
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Minneapolis, Minnesota, United States, 55455
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Tupelo, Mississippi, United States, 38801
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Saint Louis, Missouri, United States, 63110
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Omaha, Nebraska, United States, 68198
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Las Vegas, Nevada, United States, 89109
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New Brunswick, New Jersey, United States
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Buffalo, New York, United States, 14263
New York, New York, United States, 10019
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Chapel Hill, North Carolina, United States, 27516
Durham, North Carolina, United States, 27710
Raleigh, North Carolina, United States, 27607
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Cleveland, Ohio, United States, 44195
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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
Nashville, Tennessee, United States, 37203
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Dallas, Texas, United States, 75246
Round Rock, Texas, United States, 78681
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Salt Lake City, Utah, United States, 84112
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Norfolk, Virginia, United States, 23502
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Seattle, Washington, United States, 98104
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Madison, Wisconsin, United States, 53705
Milwaukee, Wisconsin, United States, 53226
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Concord, New South Wales, Australia, 2139
Darlinghurst, New South Wales, Australia, 2010
Kogarah, New South Wales, Australia, 2217
Port Macquarie, New South Wales, Australia, 2444
Randwick, New South Wales, Australia, 2031
Wahroonga, New South Wales, Australia, 2076
Australia, Queensland
Milton, Queensland, Australia, 4064
South Brisbane, Queensland, Australia, 4101
Woolloongabba, Queensland, Australia, 4102
Australia, Victoria
Box Hill, Victoria, Australia, 3128
Wodonga, Victoria, Australia, 3690
Australia, Western Australia
Subiaco, Western Australia, Australia
Canada, British Columbia
Kelowna, British Columbia, Canada, V1Y 5L3
Vancouver, British Columbia, Canada, V57 4E6
Canada, Ontario
London, Ontario, Canada, N6A 4L6
Toronto, Ontario, Canada, M4N 3M5
Toronto, Ontario, Canada, M5G 2M9
Dublin, Ireland, 24
Dublin, Ireland, 7
United Kingdom
Bath, England, United Kingdom, BA1 3NG
Cambridge, England, United Kingdom, CB2 0QQ
Leeds, England, United Kingdom, LS9 7TF
London, England, United Kingdom, NW1 2PG
London, England, United Kingdom, SE1 9RT
London, England, United Kingdom, W12 0HS
Manchester, England, United Kingdom, M20 4BX
Sutton, England, United Kingdom, SM2 5PT
Wirral, England, United Kingdom, CH63 4JY
Aberdeen, Scotland, United Kingdom, AB25 2ZN
Edinburgh, Scotland, United Kingdom, EH4 2XU
Glasgow, Scotland, United Kingdom, G12 0YN
Inverness, Scotland, United Kingdom, RO17
Belfast, United Kingdom
Sponsors and Collaborators

Responsible Party: Exelixis Identifier: NCT01522443     History of Changes
Other Study ID Numbers: XL184-306
First Posted: January 31, 2012    Key Record Dates
Results First Posted: May 23, 2018
Last Update Posted: May 23, 2018
Last Verified: April 2018

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
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Sensory System Agents
Peripheral Nervous System Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action