Lenvatinib in Recurrent and/or Metastatic Adenoid Cystic Carcinomas of the Salivary Glands: ACC-LEN14
Status:
Completed
Trial end date:
2019-06-01
Target enrollment:
Participant gender:
Summary
ACC is rare and represent approximately 25% of salivary gland carcinomas. The standard
treatment is surgical excision followed by radiotherapy in selected cases. The disease is
characterized by a progressive course with local and distant recurrences. First-line
treatment is palliative chemotherapy that had modest results. Expression of the epidermal
growth factor receptor in ACC of salivary origin has been reported. Several papers report
that a high percentage of ACCs carries a chromosome translocation that results in the
overexpression of the oncogene MYB, which is involved in cell proliferation, apoptosis,
differentiation and in upregulation of several growth and angiogenetic factors contributing
to the autocrine activation of the FGFR and VEGFR-mediated angiogenesis. Recently two whole
genome sequencing of several ACC tumor/normal pairs have found mutations in genes involved in
the FGF/IGF/PI3K pathway corroborating the hypothesis that this subset might benefit from
inhibitors of this pathway. Based on these premises several antiangiogenic drugs and FGFR
inhibitors are currently under investigation and a response rate of 11% was observed in ACC.
Lenvatinib is an oral multiple RTK inhibitor targeting VEGFR-1-3, FGFR-1-4, RET, c-KIT, and
PDGFR. On February 13, 2015 the drug has been approved by FDA for the treatment of patients
with locally recurrent or metastatic, radioactive iodine-refractory differentiated thyroid
cancer. Based on preclinical and clinical data, the investigators believe that targeting
angiogenesis, FGFR pathway and tumor microenvironment might represent a rational basis to
test Lenvatinib in patients with relapsed and/or metastatic ACC.
Phase:
Phase 2
Details
Lead Sponsor:
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano