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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Exelixis
ClinicalTrials.gov Identifier:
NCT01522443
First received: January 13, 2012
Last updated: September 4, 2014
Last verified: September 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: October 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
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 ClinicalTrials.gov identifier: NCT01522443

  Hide Study Locations
Locations
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
United States, District of Columbia
Washington, District of Columbia, United States, 20037
United States, Florida
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
United States, Iowa
Iowa City, Iowa, United States, 52242
United States, Kansas
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, 48202
Detroit, Michigan, United States, 48201
United States, Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Mississippi
Tupelo, Mississippi, United States, 38801
United States, Missouri
St. Louis, Missouri, United States, 63110
United States, Nebraska
Omaha, Nebraska, United States, 68198
United States, Nevada
Las Vegas, Nevada, United States, 89109
United States, New Jersey
New Brunswick, New Jersey, United States
United States, New York
Buffalo, New York, United States, 14263
New York, New York, United States, 10065
New York, New York, United States, 10019
New York, New York, United States, 10022
United States, North Carolina
Chapel Hill, North Carolina, United States, 27516
Durham, North Carolina, United States, 27710
Raleigh, North Carolina, United States, 27607
United States, Ohio
Cleveland, Ohio, United States, 44195
United States, Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States, 15232
United States, South Dakota
Watertown, South Dakota, United States, 57201
United States, Tennessee
Memphis, Tennessee, United States, 38120
Nashville, Tennessee, United States, 37203
United States, Texas
Dallas, Texas, United States, 75246
Round Rock, Texas, United States, 78681
United States, Utah
Salt Lake City, Utah, United States, 84112
United States, Virginia
Norfolk, Virginia, United States, 23502
United States, Washington
Seattle, Washington, United States, 98104
United States, Wisconsin
Madison, Wisconsin, United States, 53705
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
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
Ireland
Dublin, Ireland, 7
Dublin, Ireland, 24
United Kingdom
Bath, England, United Kingdom, BA1 3NG
Cambridge, England, United Kingdom, CB2 0QQ
Leeds, England, United Kingdom, LS9 7TF
London, England, United Kingdom, SE1 9RT
London, England, United Kingdom, W12 0HS
London, England, United Kingdom, NW1 2PG
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
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: September 4, 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
CRPC

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

ClinicalTrials.gov processed this record on October 01, 2014