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A Pilot Study of the Effects of Cabozantinib (XL184) on Bone Turnover and the Microenvironment in Men With Non-Metastatic and Metastatic Castration-Resistant Prostate Cancer

18 Years
Not Enrolling
Adenocarcinoma of the Prostate, Castration-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage III Prostate Cancer, Stage IV Prostate Cancer

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Trial Information

A Pilot Study of the Effects of Cabozantinib (XL184) on Bone Turnover and the Microenvironment in Men With Non-Metastatic and Metastatic Castration-Resistant Prostate Cancer


I. To assess the impact of cabozantinib on markers of bone turnover and microenvironment in
men with non-metastatic castration-resistant prostate cancer and to compare the findings in
men with metastatic castration-resistant prostate cancer.


I. To describe the associated changes in dynamic histomorphometry at baseline and after 6
weeks of cabozantinib therapy in men with non-metastatic castration-resistant prostate

II. To characterize, describe, and compare the effects of cabozantinib in men with
non-metastatic and metastatic bone disease with respect to the following measurements at
baseline and on therapy: markers of bone metabolism in blood including bone specific
alkaline phosphatase, alkaline phosphatase, lactate dehydrogenase (LDH); changes in markers
of apoptosis, proliferation, and angiogenesis in biopsy specimens from both bone and soft
tissue during therapy with cabozantinib.


I. Radiographic disease responses and toxicities will be monitored for all patients.


Patients receive cabozantinib orally (PO) once daily (QD) in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Inclusion Criteria

Key Inclusion Criteria

- The subject has a proven histologic diagnosis of prostate adenocarcinoma, but may
have undergone prior surgery and/or radiation

- The subject must currently have castration resistant prostate cancer defined as 2
serial rising prostate-specific antigens (PSAs) with a castrate level of testosterone
(< 50 ng/dL)

- A subject with non-metastatic castration-resistant prostate cancer (CRPC) may not
have received prior chemotherapy unless in the neoadjuvant or adjuvant setting > 24
months ago and may not have received prior zoledronic acid or denosumab

- A subject with metastatic CRPC must have bone metastases accessible for biopsy by
computed tomography (CT) guidance

- The subject must be willing to undergo sequential biopsy of bone or bone metastases

- Adequate organ and bone marrow function.

- The subject is capable of understanding and complying with the protocol requirements
and has signed the informed consent document

Key Exclusion Criteria

- Prior treatment with cabozantinib and other met inhibitors

- Cytotoxic chemotherapy or biologic agents within 3 weeks of study treatment

- Recent radiation therapy (3 months for thoracic cavity, 14 days for bone or brain
metastasis, 28 days for other sites) or radionuclide treatment within 6 weeks of
starting study drug.

- The subject has received any other type of investigational agent within 28 days
before the first dose of study treatment

- The subject has not recovered from toxicities due to all prior therapies except
alopecia and other non-clinically significant adverse events (AEs)

- The subject has primary brain tumor or active brain metastases or epidural

- Coagulation tests need to be adequate for the study

- The subject requires concomitant treatment, in therapeutic doses, with anticoagulants
such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa
inhibitors, or antiplatelet agents (eg, clopidogrel); low dose aspirin (=< 81
mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight
heparin (LMWH) are permitted

- The subject requires chronic concomitant treatment of strong cytochrome P450, family
3, subfamily A, polypeptide 4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin,
carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort)

- History of clinically significant gastrointestinal bleeding

- The subject has uncontrolled, significant intercurrent or recent illness

- The subject is unable to swallow tablets

- The subject has a corrected QT interval (QTcF) > 500 ms within 28 days before day 1
of cycle 1

- The subject has a previously identified allergy or hypersensitivity to components of
the study treatment formulation or to tetracycline

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Change in urinary N-telopeptide (uNTX)

Outcome Description:

Will be analyzed after log-transformation.

Outcome Time Frame:

Baseline and 6 weeks

Safety Issue:


Principal Investigator

Celestia Higano

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

June 2013

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Castration-Resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Stage III Prostate Cancer
  • Stage IV Prostate Cancer
  • Prostate cancer
  • Bone metastases
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms



Seattle Cancer Care Alliance/University of WashingtonSeattle, Washington  98109