Cabozantinib in Treating Men With Castration-Resistant Prostate Cancer

This study is currently recruiting participants.
Verified March 2014 by University of Washington
Sponsor:
Collaborators:
Prostate Cancer Foundation
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT01703065
First received: October 5, 2012
Last updated: March 17, 2014
Last verified: March 2014

October 5, 2012
March 17, 2014
September 2013
April 2016   (final data collection date for primary outcome measure)
Change in urinary N-telopeptide (uNTX) [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
Will be analyzed after log-transformation.
Same as current
Complete list of historical versions of study NCT01703065 on ClinicalTrials.gov Archive Site
  • Toxicity assessed using CTCAE version 4.0 [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: Yes ]
    Toxicity will be described by grade and frequency.
  • Progression-free survival [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Kaplan-Meier methods will be used to report progression-free survival.
  • Time to progression [ Time Frame: From date of registration to date of progressive disease, assessed up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Kaplan-Meier methods will be used to report time to progression.
  • Objective response [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Proportions and 95% binomial confidence intervals will be reported for objective response.
  • PSA response [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Proportions and 95% binomial confidence intervals will be reported for PSA response.
  • Duration of response [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Mean and the corresponding standard deviation will be used to describe the duration of response among responders.
  • Changes in dynamic histomorphometry of involved and uninvolved bone [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
    Logistic models will be used.
  • Changes in bone and serum markers of bone metabolism [ Time Frame: Baseline, 6 weeks and 12 weeks ] [ Designated as safety issue: No ]
    Will be explored using a linear mixed model to determine if there is a difference in these markers over time between patients with progressive disease and those without.
  • Toxicity assessed using CTCAE version 4.0 [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: Yes ]
    Toxicity will be described by grade and frequency.
  • Progression-free survival [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Kaplan-Meier methods will be used to report progression-free survival.
  • Time to progression [ Time Frame: From date of registration to date of progressive disease, assessed up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Kaplan-Meier methods will be used to report time to progression.
  • Objective response [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Proportions and 95% binomial confidence intervals will be reported for objective response.
  • PSA response [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Proportions and 95% binomial confidence intervals will be reported for PSA response.
  • Duration of response [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Mean and the corresponding standard deviation will be used to describe the duration of response among responders.
  • Changes in dynamic histomorphometry of involved and uninvolved bone [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    Logistic models will be used.
  • Changes in bone and serum markers of bone metabolism [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
    Will be explored using a linear mixed model to determine if there is a difference in these markers over time between patients with progressive disease and those without.
  • Changes in MET, AKT, FASN and VEGFR expression and phosphorylation status (activation) in osteoblasts or osteoclasts and prostate cancer cells from bone biopsy specimens [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
    Will be explored using a linear mixed model to determine if there is a difference in these markers over time between patients with progressive disease and those without.
Not Provided
Not Provided
 
Cabozantinib in Treating Men With Castration-Resistant Prostate Cancer
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

This pilot clinical trial studies cabozantinib in treating men with castration-resistant prostate cancer. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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.

Interventional
Not Provided
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adenocarcinoma of the Prostate
  • Castration-resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Stage III Prostate Cancer
  • Stage IV Prostate Cancer
  • Drug: cabozantinib-s-malate
    Given PO
    Other Names:
    • BMS-907351
    • Cometriq
    • XL184
  • Other: laboratory biomarker analysis
    Correlative studies
Experimental: Treatment (cabozantinib)
Patients receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: cabozantinib-s-malate
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
34
Not Provided
April 2016   (final data collection date for primary outcome measure)

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
Male
18 Years and older
No
Not Provided
United States
 
NCT01703065
7819, NCI-2012-01898, P30CA015704
Yes
University of Washington
University of Washington
  • Prostate Cancer Foundation
  • National Cancer Institute (NCI)
Principal Investigator: Celestia Higano Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
University of Washington
March 2014

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