Study of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men With Previously Treated Symptomatic Castration-resistant Prostate Cancer
Condition: Prostate Cancer; Castration Resistant Prostate Cancer; Pain; Prostatic Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: cabozantinib; mitoxantrone; prednisone
Intervention description: Tablets taken orally once daily.; Given by IV once every 3 weeks.; Taken twice a day orally by mouth. Commercially-obtained prednisone tablets will be over-encapsulated in order to blind identity.
Intervention MeSH terms: Prednisone; Mitoxantrone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 119.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: prostate cancer; castration resistant prostate cancer; bone pain; CRPC

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.