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

April 23, 2018 updated by: Exelixis

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

119

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • 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
    • Queensland
      • Milton, Queensland, Australia, 4064
      • South Brisbane, Queensland, Australia, 4101
      • Woolloongabba, Queensland, Australia, 4102
    • Victoria
      • Box Hill, Victoria, Australia, 3128
      • Wodonga, Victoria, Australia, 3690
    • Western Australia
      • Subiaco, Western Australia, Australia
  • Canada
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 5L3
      • Vancouver, British Columbia, Canada, V57 4E6
    • Ontario
      • London, Ontario, Canada, N6A 4L6
      • Toronto, Ontario, Canada, M5G 2M9
      • Toronto, Ontario, Canada, M4N 3M5
  • Ireland
      • Dublin, Ireland, 24
      • Dublin, Ireland, 7
  • United Kingdom
      • Belfast, United Kingdom
    • England
      • 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
    • Scotland
      • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Glasgow, Scotland, United Kingdom, G12 0YN
      • Inverness, Scotland, United Kingdom, RO17
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
    • California
      • La Jolla, California, United States, 92093
      • Los Angeles, California, United States, 90073
      • Los Angeles, California, United States, 90024
      • 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
    • Colorado
      • Aurora, Colorado, United States, 80012
      • Littleton, Colorado, United States, 80122
    • District of Columbia
      • Washington, District of Columbia, United States, 20037
    • Florida
      • Boca Raton, Florida, United States, 33486
    • Georgia
      • Athens, Georgia, United States, 30607
    • Illinois
      • Chicago, Illinois, United States, 60611
    • Indiana
      • Indianapolis, Indiana, United States, 46202
    • Iowa
      • Iowa City, Iowa, United States, 52242
    • Kansas
      • Westwood, Kansas, United States, 66025
    • Kentucky
      • Louisville, Kentucky, United States, 40202
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
    • Maryland
      • Baltimore, Maryland, United States, 21231
    • Michigan
      • Detroit, Michigan, United States, 48201
      • Detroit, Michigan, United States, 48202
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
    • Mississippi
      • Tupelo, Mississippi, United States, 38801
    • Missouri
      • Saint Louis, Missouri, United States, 63110
    • Nebraska
      • Omaha, Nebraska, United States, 68198
    • Nevada
      • Las Vegas, Nevada, United States, 89109
    • New Jersey
      • New Brunswick, New Jersey, United States
    • New York
      • Buffalo, New York, United States, 14263
      • New York, New York, United States, 10065
      • New York, New York, United States, 10022
      • New York, New York, United States, 10019
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27516
      • Durham, North Carolina, United States, 27710
      • Raleigh, North Carolina, United States, 27607
    • Ohio
      • Cleveland, Ohio, United States, 44195
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
    • South Dakota
      • Watertown, South Dakota, United States, 57201
    • Tennessee
      • Memphis, Tennessee, United States, 38120
      • Nashville, Tennessee, United States, 37203
    • Texas
      • Dallas, Texas, United States, 75246
      • Round Rock, Texas, United States, 78681
    • Utah
      • Salt Lake City, Utah, United States, 84112
    • Virginia
      • Norfolk, Virginia, United States, 23502
    • Washington
      • Seattle, Washington, United States, 98104
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
      • Milwaukee, Wisconsin, United States, 53226

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Pain response was measured at Week 6 and Week 12 by self-reports of subjects

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
BSR was measured at the end of Week 12 as determined by the IRF
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.
OS was measured at the time of randomization until 78 deaths

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Exelixis

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2012

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

January 13, 2015

Study Registration Dates

First Submitted

January 13, 2012

First Submitted That Met QC Criteria

January 27, 2012

First Posted (Estimate)

January 31, 2012

Study Record Updates

Last Update Posted (Actual)

May 23, 2018

Last Update Submitted That Met QC Criteria

April 23, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XL184-306

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pain

Clinical Trials on cabozantinib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ecuador

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe