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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Exelixis
ClinicalTrials.gov Identifier:
NCT01522443
First received: January 13, 2012
Last updated: September 4, 2014
Last verified: September 2014

January 13, 2012
September 4, 2014
March 2012
October 2014   (final data collection date for primary outcome measure)
Confirmed pain response at Week 12 durable since Week 6 [ Time Frame: Week 6 and 12 ] [ Designated as safety issue: No ]
Subjects will self-report information on pain and health-related quality of life via an interactive voice recognition system
Same as current
Complete list of historical versions of study NCT01522443 on ClinicalTrials.gov Archive Site
  • Bone scan response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Bone scans will be evaluated by an independent radiology facility for response
  • Overall survival [ Time Frame: through 28 months after study start ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Study of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men With Previously Treated Symptomatic Castration-resistant Prostate Cancer
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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Prostate Cancer
  • Castration Resistant Prostate Cancer
  • Pain
  • Prostatic Neoplasms
  • Drug: cabozantinib
    Tablets taken orally once daily.
  • 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.
  • 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.

    Intervention: Drug: cabozantinib
  • 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.

    Interventions:
    • Drug: mitoxantrone
    • Drug: prednisone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
246
Not Provided
October 2014   (final data collection date for primary outcome measure)

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.
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Australia,   United States,   United Kingdom,   Canada,   Ireland
 
NCT01522443
XL184-306
Yes
Exelixis
Exelixis
Not Provided
Not Provided
Exelixis
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP