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

NCT ID: NCT01522443

Last Updated: 2018-05-23

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

119 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-03-31

Study Completion Date

2015-01-13

Brief Summary

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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.

Detailed Description

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Conditions

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Prostate Cancer Castration Resistant Prostate Cancer Pain Prostatic Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

cabozantinib

Intervention Type DRUG

Tablets taken orally once daily.

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.

Group Type ACTIVE_COMPARATOR

mitoxantrone

Intervention Type DRUG

Given by IV once every 3 weeks.

prednisone

Intervention Type DRUG

Taken twice a day orally by mouth. Commercially-obtained prednisone tablets will be over-encapsulated in order to blind identity.

Interventions

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cabozantinib

Tablets taken orally once daily.

Intervention Type DRUG

mitoxantrone

Given by IV once every 3 weeks.

Intervention Type DRUG

prednisone

Taken twice a day orally by mouth. Commercially-obtained prednisone tablets will be over-encapsulated in order to blind identity.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Exelixis

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Scottsdale, Arizona, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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Marina del Rey, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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Santa Barbara, California, United States

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Stanford, California, United States

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Aurora, Colorado, United States

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Littleton, Colorado, United States

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Washington D.C., District of Columbia, United States

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Boca Raton, Florida, United States

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Athens, Georgia, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Westwood, Kansas, United States

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Louisville, Kentucky, United States

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New Orleans, Louisiana, United States

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Baltimore, Maryland, United States

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Detroit, Michigan, United States

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Detroit, Michigan, United States

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Minneapolis, Minnesota, United States

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Tupelo, Mississippi, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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New Brunswick, New Jersey, United States

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Buffalo, New York, United States

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New York, New York, United States

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New York, New York, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Durham, North Carolina, United States

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Raleigh, North Carolina, United States

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Cleveland, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Pittsburgh, Pennsylvania, United States

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Watertown, South Dakota, United States

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Memphis, Tennessee, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Round Rock, Texas, United States

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Salt Lake City, Utah, United States

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Norfolk, Virginia, United States

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Seattle, Washington, United States

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Madison, Wisconsin, United States

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Milwaukee, Wisconsin, United States

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Concord, New South Wales, Australia

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Darlinghurst, New South Wales, Australia

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Kogarah, New South Wales, Australia

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Port Macquarie, New South Wales, Australia

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Randwick, New South Wales, Australia

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Wahroonga, New South Wales, Australia

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Milton, Queensland, Australia

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South Brisbane, Queensland, Australia

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Woolloongabba, Queensland, Australia

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Box Hill, Victoria, Australia

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Wodonga, Victoria, Australia

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Subiaco, Western Australia, Australia

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Kelowna, British Columbia, Canada

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Vancouver, British Columbia, Canada

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London, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Dublin, , Ireland

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Dublin, , Ireland

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Bath, England, United Kingdom

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Cambridge, England, United Kingdom

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Leeds, England, United Kingdom

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London, England, United Kingdom

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London, England, United Kingdom

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London, England, United Kingdom

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Manchester, England, United Kingdom

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Metropolitan Borough of Wirral, England, United Kingdom

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Sutton, England, United Kingdom

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Aberdeen, Scotland, United Kingdom

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Edinburgh, Scotland, United Kingdom

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Glasgow, Scotland, United Kingdom

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Inverness, Scotland, United Kingdom

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Belfast, , United Kingdom

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Countries

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United States Australia Canada Ireland United Kingdom

References

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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.

Reference Type DERIVED
PMID: 35779938 (View on PubMed)

Mazza 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.

Reference Type DERIVED
PMID: 34420143 (View on PubMed)

Basch 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.

Reference Type DERIVED
PMID: 33258687 (View on PubMed)

Dueck 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.

Reference Type DERIVED
PMID: 31556911 (View on PubMed)

Other Identifiers

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XL184-306

Identifier Type: -

Identifier Source: org_study_id

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