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

NCT01522443 | Terminated Phase 3 Results DMC

• 1 other identifier: XL184-306
• Study Type: interventional
• Target: 119
• Locations: 5 countries
• Sites: 82

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.

Conditions

Prostate Cancer; Castration Resistant Prostate Cancer; Pain; Prostatic Neoplasms

Keywords

prostate cancer; castration resistant prostate cancer; bone pain; CRPC

Outcome Measures

Primary Outcomes (1)

• 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.

  Pain response was measured at Week 6 and Week 12 by self-reports of subjects

Secondary Outcomes (2)

• Bone Scan Response (BSR)

  BSR was measured at the end of Week 12 as determined by the IRF

• Overall Survival (OS)

  OS was measured at the time of randomization until 78 deaths

Study Arms (2)

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.

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.

Drug: mitoxantrone; Drug: prednisone

Interventions

cabozantinib DRUG

Tablets taken orally once daily.

Cabozantinib

mitoxantrone DRUG

Given by IV once every 3 weeks.

Mitoxantrone/prednisone

prednisone DRUG

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

Mitoxantrone/prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (82)

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Scottsdale, Arizona, 85258, United States

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La Jolla, California, 92093, United States

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Los Angeles, California, 90024, United States

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Los Angeles, California, 90073, United States

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Marina del Rey, California, 90292, United States

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San Diego, California, 92123, United States

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San Francisco, California, 94115, United States

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Santa Barbara, California, 93105, United States

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Stanford, California, 94305, United States

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Aurora, Colorado, 80012, United States

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Littleton, Colorado, 80122, United States

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Washington D.C., District of Columbia, 20037, United States

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Boca Raton, Florida, 33486, United States

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Athens, Georgia, 30607, United States

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Chicago, Illinois, 60611, United States

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Indianapolis, Indiana, 46202, United States

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Iowa City, Iowa, 52242, United States

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Westwood, Kansas, 66025, United States

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Louisville, Kentucky, 40202, United States

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New Orleans, Louisiana, 70112, United States

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Baltimore, Maryland, 21231, United States

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Detroit, Michigan, 48201, United States

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Detroit, Michigan, 48202, United States

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Minneapolis, Minnesota, 55455, United States

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Tupelo, Mississippi, 38801, United States

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St Louis, Missouri, 63110, United States

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Omaha, Nebraska, 68198, United States

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Las Vegas, Nevada, 89109, United States

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New Brunswick, New Jersey, United States

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Buffalo, New York, 14263, United States

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New York, New York, 10019, United States

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New York, New York, 10022, United States

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New York, New York, 10065, United States

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Chapel Hill, North Carolina, 27516, United States

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Durham, North Carolina, 27710, United States

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Raleigh, North Carolina, 27607, United States

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Cleveland, Ohio, 44195, United States

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Oklahoma City, Oklahoma, 73104, United States

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Pittsburgh, Pennsylvania, 15232, United States

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Watertown, South Dakota, 57201, United States

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Memphis, Tennessee, 38120, United States

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Nashville, Tennessee, 37203, United States

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Dallas, Texas, 75246, United States

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Round Rock, Texas, 78681, United States

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Salt Lake City, Utah, 84112, United States

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Norfolk, Virginia, 23502, United States

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Seattle, Washington, 98104, United States

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Madison, Wisconsin, 53705, United States

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Milwaukee, Wisconsin, 53226, United States

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Concord, New South Wales, 2139, Australia

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Darlinghurst, New South Wales, 2010, Australia

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Kogarah, New South Wales, 2217, Australia

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Port Macquarie, New South Wales, 2444, Australia

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Randwick, New South Wales, 2031, Australia

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Wahroonga, New South Wales, 2076, Australia

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Milton, Queensland, 4064, Australia

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South Brisbane, Queensland, 4101, Australia

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Woolloongabba, Queensland, 4102, Australia

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Box Hill, Victoria, 3128, Australia

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Wodonga, Victoria, 3690, Australia

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Subiaco, Western Australia, Australia

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Kelowna, British Columbia, V1Y 5L3, Canada

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Vancouver, British Columbia, V57 4E6, Canada

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London, Ontario, N6A 4L6, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Dublin, 24, Ireland

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Dublin, 7, Ireland

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Bath, England, BA1 3NG, United Kingdom

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Cambridge, England, CB2 0QQ, United Kingdom

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Leeds, England, LS9 7TF, United Kingdom

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London, England, NW1 2PG, United Kingdom

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London, England, SE1 9RT, United Kingdom

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London, England, W12 0HS, United Kingdom

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Manchester, England, M20 4BX, United Kingdom

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Metropolitan Borough of Wirral, England, CH63 4JY, United Kingdom

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Sutton, England, SM2 5PT, United Kingdom

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Aberdeen, Scotland, AB25 2ZN, United Kingdom

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Edinburgh, Scotland, EH4 2XU, United Kingdom

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Glasgow, Scotland, G12 0YN, United Kingdom

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Inverness, Scotland, RO17, United Kingdom

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Belfast, United Kingdom

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Related Publications (4)

• 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.

  PMID: 35779938 DERIVED

• 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.

  PMID: 34420143 DERIVED

• 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.

  PMID: 33258687 DERIVED

• 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.

  PMID: 31556911 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms; Pain

Interventions

cabozantinib; Mitoxantrone; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Limitations and Caveats

Enrollment was stopped before planned study population size of 246 was reached (only 119 enrolled).

Results Point of Contact

• Title: Exelixis Medical Information
• Organization: Exelixis, Inc.

druginfo@exelixis.com

855-292-3935

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2012
• First Posted: January 31, 2012
• Study Start: March 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: January 13, 2015
• Last Updated: May 23, 2018
• Results First Posted: May 23, 2018

Record last verified: 2018-04

Locations

IE (2); GB (14); AU (12); CA (5); US (49)