Clinical trial NCT01522443: Study of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men With Previously Treated Symptomatic Castration-resistant Prostate Cancer
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Prostate Cancer
Castration Resistant Prostate Cancer
Pain
Prostatic Neoplasms
Keywords: prostate cancer
castration resistant prostate cancer
bone pain
CRPC
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2012-01-31
Enrollment: 119
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Pain Response at Week 6 Confirmed at Week 12, Week 12 Reported
timeFrame: Pain response was measured at Week 6 and Week 12 by self-reports of subjects
Secondary outcomes:
measure: Bone Scan Response (BSR)
timeFrame: BSR was measured at the end of Week 12 as determined by the IRF
measure: Overall Survival (OS)
timeFrame: OS was measured at the time of randomization until 78 deaths
Other outcomes:
Locations:
city: Scottsdale
country: United States
state: Arizona
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Marina Del Rey
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Santa Barbara
country: United States
state: California
city: Stanford
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Littleton
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Boca Raton
country: United States
state: Florida
city: Athens
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Iowa City
country: United States
state: Iowa
city: Westwood
country: United States
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Baltimore
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state: Maryland
city: Detroit
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state: Michigan
city: Detroit
country: United States
state: Michigan
city: Minneapolis
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state: Minnesota
city: Tupelo
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Las Vegas
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state: Nevada
city: New Brunswick
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state: New Jersey
city: Buffalo
country: United States
state: New York
city: New York
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state: New York
city: New York
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state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Pittsburgh
country: United States
state: Pennsylvania
city: Watertown
country: United States
state: South Dakota
city: Memphis
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state: Tennessee
city: Nashville
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state: Tennessee
city: Dallas
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state: Texas
city: Round Rock
country: United States
state: Texas
city: Salt Lake City
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state: Utah
city: Norfolk
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state: Virginia
city: Seattle
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state: Washington
city: Madison
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state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Concord
country: Australia
state: New South Wales
city: Darlinghurst
country: Australia
state: New South Wales
city: Kogarah
country: Australia
state: New South Wales
city: Port Macquarie
country: Australia
state: New South Wales
city: Randwick
country: Australia
state: New South Wales
city: Wahroonga
country: Australia
state: New South Wales
city: Milton
country: Australia
state: Queensland
city: South Brisbane
country: Australia
state: Queensland
city: Woolloongabba
country: Australia
state: Queensland
city: Box Hill
country: Australia
state: Victoria
city: Wodonga
country: Australia
state: Victoria
city: Subiaco
country: Australia
state: Western Australia
city: Kelowna
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Dublin
country: Ireland
city: Dublin
country: Ireland
city: Bath
country: United Kingdom
state: England
city: Cambridge
country: United Kingdom
state: England
city: Leeds
country: United Kingdom
state: England
city: London
country: United Kingdom
state: England
city: London
country: United Kingdom
state: England
city: London
country: United Kingdom
state: England
city: Manchester
country: United Kingdom
state: England
city: Sutton
country: United Kingdom
state: England
city: Wirral
country: United Kingdom
state: England
city: Aberdeen
country: United Kingdom
state: Scotland
city: Edinburgh
country: United Kingdom
state: Scotland
city: Glasgow
country: United Kingdom
state: Scotland
city: Inverness
country: United Kingdom
state: Scotland
city: Belfast
country: United Kingdom
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.