Cabozantinib (XL184) in Men With Castrate-Resistant Prostate Cancer
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Dose-Finding Pilot Study of XL184 in Men With Castrate-Resistant Prostate Cancer and Bone Metastases|
- 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.
- 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.
|Study Start Date:||April 2011|
|Estimated Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
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.
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Matthew R Smith, M.D., Ph.D.||Massachusetts General Hospital|