CMTTdb

An integrated database for cancer molecular targeted thearpies

Entry Detail


General information
Database:DB00204
Objective:(18)Ffluoride PET quantitatively images bone metabolism and may serve as a pharmacodynamic assessment for systemic therapy such as dasatinib, a potent SRC kinase inhibitor, with activity in bone.
Authors:Yu EY, et al
Title:Castrationresistant prostate cancer bone metastasis response measured by 18Ffluoride PET after treatment with dasatinib and correlation with progression free survival: results from American College of Radiology Imaging Network 6687.
Journal:J Nucl Med.
Year:2015
PMID:25635138
Trial Design
Clinical Trial Id:NCT00918385
Agent:dasatinib
Target:Protooncogene tyrosineprotein kinase SRC
Abl
Protooncogene tyrosineprotein kinase LCK
Protooncogene tyrosineprotein kinase Fyn
Cancer Type:prostate cancer
Cancer Subtype:Castrationresistant prostate cancer bone metastasis
Therapy Type:mono
Therapeutic Combination Type:NA
Therapeutic Combination Content:NA
Study Type:a multicenter metastatic castrationresistant prostate cancer (CRPC) tissue biomarkerguided therapeutic trial
Key Patients Feature:Castrationresistant prostate cancer patients with bone metastasis
Biomarker:bone alkaline phosphatase and PSA
Biomark Analysis:Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity.
Control Group Info:single arm
Treatment Info:pts underwent (18)Ffluoride PET before and 12 weeks after initiation of dasatinib (100 mg daily). Dynamic imaging was performed over a 15cm field of view for trial assessments.
Primary End Point:changes in (18)Ffluoride incorporation in tumor and normal bone occurred in response to dasatinib.
Secondary End Point:Other endpoints included differential effect of dasatinib between (18)Ffluoride incorporation in tumor and normal bone, (18)Ffluoride transport in bone metastases, correlation with progression free survival (PFS), prostatespecific antigen, and markers of bone turnover.
Patients Number:18
Trial Results
DLT_MTD:NA
Objective Response Rate:Statistically significant changes in response to dasatinib were identified by the SUVmaxavg (average of maximum standardized uptake value [SUVmax] for up to 5 tumors within the dynamic field of view) in bone metastases (P = 0.0002), with a significant differential (18)Ffluoride PET response between tumor and normal bone (P < 0.0001).
Disease Control Rate:Changes by SUVmaxavg correlated with bone alkaline phosphatase (P = 0.0014) but not prostatespecific antigen (P = 0.47).
Median Time to Progression:NA
Median PFS A vs. C:Changes in (18)Ffluoride incorporation in bone metastases had borderline correlation with PFS by SUVmaxavg (hazard ratio, 0.91; 95% confidence interval, 0.821.00; P = 0.056).
Median OS A vs. C:NA
Adverse Event(agent arm):NA
Conclusions:This trial provides evidence of the ability (18)Ffluoride PET to delineate treatment response of dasatinib in CRPC bone metastases with borderline correlation with PFS.