Phase II Pazopanib Study in Advanced Dermatofibrosarcomas
Status:
Terminated
Trial end date:
2014-04-01
Target enrollment:
Participant gender:
Summary
In relation to the activation of PDGF-mediated signalization due to the fusion gene
COL1A1-PDGFb in DFSP, imatinib (800mg/day) has shown activity in advanced DFSP and has became
the reference treatment option for these patients. Yet the activity observed does not allow
for a downstaging compatible with successful resection in a number of patients and does not
prevent subsequent tumour progression in case of residual tumour.Pazopanib in relation to 1)
its multi tyrosine kinase inhibiting activity (VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α, PDGFR-β
and c-kit with IC50 values of 10, 30, 47, 71, 84, and 74 nM, respectively) involving in
particular PDGFR, and VEGFR which has been shown to be activated in DFSP, 2) its antitumour
activity in sarcomas patients, and 3) its acceptable safety profile, is a logical candidate
for therapeutic trials in DFSP both in patients not expected to derive a sufficient benefit
from imatinib and in patients failing imatinib mesylate. Moreover, using quantitative RT-PCR
and immunohistochemistry we have recently demonstrated high levels of VEGF and VEGFR2
expression in dermatofibrosarcoma.