Cabozantinib (XL184) in Men With Castrate-Resistant Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Matthew R. Smith, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01347788
First received: April 11, 2011
Last updated: July 9, 2013
Last verified: July 2013

April 11, 2011
July 9, 2013
April 2011
May 2013   (final data collection date for primary outcome measure)
Post-Treatment change in bone scan from baseline to week 6 [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
Bone scans will be centrally reviewed and categorized as complete resolution, significant improvement, stable disease, or unequivocal progression based on comparison of week 6 and baseline imaging. An adaptive response design to determine the lowest effective XL184 dose among three dose levels (dose level +1, dose level 0 and dose level +1) will be employed.
Post-Treatment change in bone scan from baseline to week 6 [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
Bone scans will be centrally reviewed and categorized as complete resolution, significant improvement, stable disease, or unequivocal progression based on comparison of week 6 and baseline imgaing. An adaptive response design to determine the lowest effective XL184 dose among three dose levels (dose level +1, dose level 0 and dose level +1) will be employed.
Complete list of historical versions of study NCT01347788 on ClinicalTrials.gov Archive Site
  • Markers of bone turnover (including BAP and NTx levels) [ Time Frame: Baseline, every 21 days (through Cycle 5) and when participant is removed from the study ] [ Designated as safety issue: No ]
    BAP and NTx levels will be summarized as median (range) and mean (the standard deviation) at baseline and each time point. Percent change from baseline will be summarized overtime.
  • Effect on circulating tumor cells categorized as normal versus abnormal [ Time Frame: Baseline, every 21 days (through Cycle 5) and when participant is removed from the study ] [ Designated as safety issue: No ]
    CRC counts assessed by Veridex assay will be categorized as normal versus abnormal. The proportion of patients with abnormal CTC counts will be summarized at baseline and each time point. Change on CTC status from baseline will be tabulated as a two by two contingency table over time.
  • Markers of bone turnover (including BAP and NTx levels) [ Time Frame: Baseline, every 21 days (through Cycle 5) and when participant is removed from the study ] [ Designated as safety issue: No ]
    BAP and NTx levels will be summarized as median (range) and mean (the standard deviation) at baseline and each time point. Percent change from baseline will be summarized overtime.
  • Effect on circulating tumor cells categorized as normal versus abnormal [ Time Frame: Baseline, every 21 days (through Cycle 5) and when participant is removed from the study ] [ Designated as safety issue: No ]
    CRC counts assessed by Veridex assay will be catergorized as normal versus abnormal. The porportion of patients with abnormal CTC counts will be summarized at baseline and each time point. Change on CTC status from baseline will be tabulated as a two by two contigency table over time.
Not Provided
Not Provided
 
Cabozantinib (XL184) in Men With Castrate-Resistant Prostate Cancer
Dose-Finding Pilot Study of XL184 in Men With Castrate-Resistant Prostate Cancer and Bone Metastases

XL184 is a new drug that is being developed to treat cancer. XL184 works by blocking the "angiogenesis," or the growth of new blood vessels, to the tumor. This is similar to how several other cancer drugs work but in addition XL184 also blocks other pathways that may be responsible for allowing cancer cells to become resistant to these other "anti-angiogenic" treatments. So far XL184 has been investigated in treating brain cancer and a rare form of thyroid cancer. This study will explore lower doses of XL184 with the goal to find the most effective, safe, and tolerable dose without undesirable side effects.

XL184 will be taken by mouth daily. The first five treatment cycles will be 21 days. All cycles after that will be 42 days long. Patients will keep a diary to record study drug dosing.

During the screening phase patients will receive a physical exam, blood and urine tests, a bone scan, a CT of the abdomen and pelvis, and an MRI scan of total body. On Day 1 of each cycle patients will receive a physical exam and blood and urine tests. Bone scan, CT and MRI scans will be performed at the start of cycles 3 and 5, and then repeated once every 12 weeks.

Patients will continue to receive study treatment as long as they are receiving benefit from the treatment, do not experience any severe or unmanageable side effects, and disease does not get any worse.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Adenocarcinoma
Drug: XL184
Starting dose of 50 mg PO QD
Not Provided
Lee RJ, Saylor PJ, Michaelson MD, Rothenberg SM, Smas ME, Miyamoto DT, Gurski CA, Xie W, Maheswaran S, Haber DA, Goldin JG, Smith MR. A Dose-Ranging Study of Cabozantinib in Men with Castration-Resistant Prostate Cancer and Bone Metastases. Clin Cancer Res. 2013 May 15. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
May 2013
May 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed prostate adenocarcinoma
  • Bone metastases confirmed by bone scan
  • Current androgen deprivation therapy
  • Castration-resistant disease based on progression in bone and/or PSA progression
  • Recovered from toxicities related to prior treatment, except alopecia, lymphopenia, other non-clinically significant adverse events
  • Life expectancy of greater than 3 months
  • Normal organ and marrow function
  • Capable of understanding and complying with the protocol requirements
  • Agree to use medically accepted methods of contraception
  • Able to swallow capsules

Exclusion Criteria:

  • More than two prior chemotherapy regimens for metastatic prostate cancer
  • Known untreated, symptomatic or uncontrolled brain metastases
  • Serious or unhealed wound
  • Treatment with anticoagulants
  • Previously identified allergy or hypersensitivity to components of the study treatment formulation
  • History of a different malignancy unless disease-free for at least 5 years, or basal or squamous cell carcinoma of the skin
  • Current antiretroviral therapy
  • Uncontrolled hypertension
  • Uncontrolled intercurrent illness
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01347788
11-005
Yes
Matthew R. Smith, MD, PhD, Massachusetts General Hospital
Massachusetts General Hospital
Not Provided
Principal Investigator: Matthew R Smith, M.D., Ph.D. Massachusetts General Hospital
Massachusetts General Hospital
July 2013

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