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Cabozantinib in Treating Men With Castration-Resistant Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 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: September 15, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention
Adenocarcinoma of the Prostate
Castration-resistant Prostate Cancer
Recurrent Prostate Cancer
Stage III Prostate Cancer
Stage IV Prostate Cancer
Drug: cabozantinib-s-malate
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Change in urinary N-telopeptide (uNTX) [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
    Will be analyzed after log-transformation.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 34
Study Start Date: September 2013
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cabozantinib)
Patients receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.
Drug: cabozantinib-s-malate
Given PO
Other Names:
  • BMS-907351
  • Cometriq
  • XL184
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01703065

Locations
United States, Washington
Seattle Cancer Care Alliance/University of Washington Recruiting
Seattle, Washington, United States, 98109
Contact: Celestia S. Higano    206-288-1136      
Principal Investigator: Celestia S. Higano         
Sponsors and Collaborators
University of Washington
Prostate Cancer Foundation
Investigators
Principal Investigator: Celestia Higano Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT01703065     History of Changes
Other Study ID Numbers: 7819, NCI-2012-01898, P30CA015704
Study First Received: October 5, 2012
Last Updated: September 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Washington:
Prostate cancer
Bone metastases

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on November 24, 2014