Prostate CancerPhase 3COMET-2NCT01522443
Study of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men With Previously Treated Symptomatic Castration-resistant Prostate Cancer
A Phase 3 study testing cabozantinib, mitoxantrone and prednisone in people with Prostate Cancer and Castration Resistant Prostate Cancer, run by Exelixis at 82 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer, Castration Resistant Prostate Cancer, Pain
- What is being tested?
- cabozantinib, mitoxantrone and prednisone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 82 sitesin 5 countries
- Study dates
- Mar 2012to 13 Jan 2015
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
82 sites in 5 countries.
82 sites in 5 countries
United States49 sites
Study site
Athens, Georgia, 30607
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Aurora, Colorado, 80012
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Baltimore, Maryland, 21231
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Boca Raton, Florida, 33486
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Buffalo, New York, 14263
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Chapel Hill, North Carolina, 27516
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Chicago, Illinois, 60611
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Cleveland, Ohio, 44195
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Dallas, Texas, 75246
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Detroit, Michigan, 48201
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Detroit, Michigan, 48202
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Durham, North Carolina, 27710
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Indianapolis, Indiana, 46202
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Iowa City, Iowa, 52242
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La Jolla, California, 92093
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Las Vegas, Nevada, 89109
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Littleton, Colorado, 80122
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Los Angeles, California, 90024
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Los Angeles, California, 90073
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Louisville, Kentucky, 40202
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Madison, Wisconsin, 53705
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Marina del Rey, California, 90292
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Memphis, Tennessee, 38120
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Milwaukee, Wisconsin, 53226
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Minneapolis, Minnesota, 55455
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Nashville, Tennessee, 37203
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New Brunswick, New Jersey
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New Orleans, Louisiana, 70112
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New York, New York, 10019
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New York, New York, 10022
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New York, New York, 10065
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Norfolk, Virginia, 23502
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Oklahoma City, Oklahoma, 73104
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Omaha, Nebraska, 68198
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Pittsburgh, Pennsylvania, 15232
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Raleigh, North Carolina, 27607
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Round Rock, Texas, 78681
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Salt Lake City, Utah, 84112
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San Diego, California, 92123
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San Francisco, California, 94115
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Santa Barbara, California, 93105
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Scottsdale, Arizona, 85258
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Seattle, Washington, 98104
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St Louis, Missouri, 63110
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Stanford, California, 94305
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Tupelo, Mississippi, 38801
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Washington D.C., District of Columbia, 20037
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Watertown, South Dakota, 57201
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Westwood, Kansas, 66025
United Kingdom14 sites
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Aberdeen, Scotland, AB25 2ZN
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Bath, England, BA1 3NG
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Belfast
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Cambridge, England, CB2 0QQ
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Edinburgh, Scotland, EH4 2XU
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Glasgow, Scotland, G12 0YN
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Inverness, Scotland, RO17
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Leeds, England, LS9 7TF
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London, England, NW1 2PG
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London, England, SE1 9RT
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London, England, W12 0HS
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Manchester, England, M20 4BX
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Metropolitan Borough of Wirral, England, CH63 4JY
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Sutton, England, SM2 5PT
Australia12 sites
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Box Hill, Victoria, 3128
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Concord, New South Wales, 2139
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Darlinghurst, New South Wales, 2010
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Kogarah, New South Wales, 2217
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Milton, Queensland, 4064
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Port Macquarie, New South Wales, 2444
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Randwick, New South Wales, 2031
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South Brisbane, Queensland, 4101
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Subiaco, Western Australia
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Wahroonga, New South Wales, 2076
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Wodonga, Victoria, 3690
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Woolloongabba, Queensland, 4102
Canada5 sites
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Kelowna, British Columbia, V1Y 5L3
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London, Ontario, N6A 4L6
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Toronto, Ontario, M4N 3M5
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Toronto, Ontario, M5G 2M9
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Vancouver, British Columbia, V57 4E6
About this study
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
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.
- Being tested
- cabozantinib, mitoxantrone, prednisone
- Keywords
- prostate cancer, castration resistant prostate cancer, bone pain, CRPC
- Medical subject headings
- Prostatic Neoplasms, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cabozantinibDrug
Tablets taken orally once daily.
mitoxantroneDrug
Given by IV once every 3 weeks.
prednisoneDrug
Taken twice a day orally by mouth. Commercially-obtained prednisone tablets will be over-encapsulated in order to blind identity.
| Study group | Role | What they receive |
|---|---|---|
| Cabozantinib | Experimental | 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. Receives: Drug: cabozantinib |
| Mitoxantrone/prednisone | Active comparator | Subjects randomized to the mitoxantrone + prednisone arm will also receive placebo cabozantinib tablets.
There will be a maximum of 10 infusions for mitoxantrone. Receives: Drug: mitoxantrone; Drug: prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain Response at Week 6 Confirmed at Week 12, Week 12 Reported
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.
Measured: Pain response was measured at Week 6 and Week 12 by self-reports of subjects
Secondary outcomes (2)
Bone Scan Response (BSR)
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.
Measured: BSR was measured at the end of Week 12 as determined by the IRF
Overall Survival (OS)
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.
Measured: OS was measured at the time of randomization until 78 deaths
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2012 (estimated)
- Study startMar 2012
- Primary completionOct 2014
- Study completion13 Jan 2015
Why it stopped: Stopped after the outcome of cabozantinib Phase 3 CRPC study XL184-307.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by ExelixisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- Exelixis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01522443
- Sponsor's protocol ID
- XL184-306
- Acronym
- COMET-2
- Status last verified
- Apr 2018
- First submitted
- 13 Jan 2012
- Last updated
- 23 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Thanarajasingam G, Basch E, Mead-Harvey C, Bennett AV, Mazza GL, Schwab G, Roydhouse J, Rogak LJ, Dueck AC. An Exploratory Analysis of the "Was It Worth It?" Questionnaire as a Novel Metric to Capture Patient Perceptions of Cancer Treatment. Value Health. 2022 Jul;25(7):1081-1086. doi: 10.1016/j.jval.2021.11.1368. Epub 2022 Jan 3.
PubMed 35779938Mazza GL, Petersen MM, Ginos B, Langlais BT, Heon N, Gounder MM, Mahoney MR, Zoroufy AJ, Schwartz GK, Rogak LJ, Thanarajasingam G, Basch E, Dueck AC. Missing data strategies for the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Alliance A091105 and COMET-2. Qual Life Res. 2022 Apr;31(4):1069-1080. doi: 10.1007/s11136-021-02968-1. Epub 2021 Aug 21.
PubMed 34420143Basch E, Becker C, Rogak LJ, Schrag D, Reeve BB, Spears P, Smith ML, Gounder MM, Mahoney MR, Schwartz GK, Bennett AV, Mendoza TR, Cleeland CS, Sloan JA, Bruner DW, Schwab G, Atkinson TM, Thanarajasingam G, Bertagnolli MM, Dueck AC. Composite grading algorithm for the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Clin Trials. 2021 Feb;18(1):104-114. doi: 10.1177/1740774520975120. Epub 2020 Dec 1.
PubMed 33258687Dueck AC, Scher HI, Bennett AV, Mazza GL, Thanarajasingam G, Schwab G, Weitzman AL, Rogak LJ, Basch E. Assessment of Adverse Events From the Patient Perspective in a Phase 3 Metastatic Castration-Resistant Prostate Cancer Clinical Trial. JAMA Oncol. 2020 Feb 1;6(2):e193332. doi: 10.1001/jamaoncol.2019.3332. Epub 2020 Feb 13.
PubMed 31556911