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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


N/A
18 Years
N/A
Not Enrolling
Male
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


PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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
cancer.

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.

TERTIARY OBJECTIVES:

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

OUTLINE:

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:

Interventional

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:

No

Principal Investigator

Celestia Higano

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

7819

NCT ID:

NCT01703065

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

Name

Location

Seattle Cancer Care Alliance/University of WashingtonSeattle, Washington  98109