Ignite Creation Date:
2024-05-06 @ 8:56 AM
Last Modification Date:
2024-10-26 @ 12:07 PM
Study NCT ID:
NCT02860936
Status:
COMPLETED
Last Update Posted:
2019-09-03
First Post:
2016-08-02
Brief Title:
Lenvatinib in Recurrent andor Metastatic Adenoid Cystic Carcinomas of the Salivary Glands ACC-LEN14
Sponsor:
Fondazione IRCCS Istituto Nazionale dei Tumori Milano
Organization:
Fondazione IRCCS Istituto Nazionale dei Tumori Milano
Study Overview
Official Title:
Phase II Study on Lenvatinib in Recurrent andor Metastatic Adenoid Cystic Carcinomas of the Salivary Glands of the Upper Aerodigestive Tract
Status:
COMPLETED
Status Verified Date:
2019-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ACC-LEN14
Brief 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 tumornormal pairs have found mutations in genes involved in the FGFIGFPI3K 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 andor metastatic ACC
Detailed Description:
Carcinomas of the salivary glands SGCs are rare less than 1 of all cancers of the head and neck and include more than 20 malignant histotypes They can occur both in major and minor salivary glands are locally aggressive demonstrating invasiveness that leads to involvement of the facial nerve skin bone and surrounding soft tissue The standard treatment is surgical excision followed by radiotherapy in selected cases such as high-grade histotypes advanced disease and neck nodes diffusion Loco-regional recurrence occurs in 16 to 85 it can be managed in very selected cases with further surgery andor radiotherapy although the prognosis of these patients remains poor Adenoid cystic cancer ACC is the most common SGC histotype observed in metastatic subjects 60 and distant metastases are the principal cause of failure being diagnosed in 25-55 of the patients First-line treatment is palliative chemotherapy that is typically not associated with any benefit neither in response rate nor in outcome In preclinical models VEGF seems to contribute to tumor aggressiveness as well as to distant metastasization in particular in ACC Moreover about 80 of ACC are characterized by MYB-NFIB fusion gene Deregulation of MYB involves several genes including those associated with apoptosis cell cycle control and angiogenesis Clinical evidences support the use of antiangiogenic compounds in ACC Sorafenib a multi-tyrosine kinase inhibitor TKI VEGFR1-3 PDGFR RET cKIT FLT3 and axitinib a potent TKI anti VEGFR1-3 have been tested in advanced ACC obtaining a 1 of response rate suggesting some activity agents of this class of drug
Recently two whole genome sequencing of ACC tumornormal pairs have found mutations in genes involved in the FGFIGFPI3K pathway up to 30 of the cases corroborating the hypothesis that this subset might benefit from agents targeting this pathway Dovitinib a small molecule that inhibits FGFR is currently under investigation Preliminary results indicate that the drug produces objective partial responses and prolonged tumor stabilization in patients with progressive ACCs Lenvatinib has a stronger antiangiogenic effect compared to sorafenib and axitinib and has also a higher potency with regard to inhibition of FGFR-1 offering a potential opportunity to block one of the well known mechanisms of resistance to VEGFVEGFR inhibitors Lenvatinib also has a direct oncogenic effect of controlling tumor cell proliferation by inhibiting RET c-KIT and PDGFR beta as well as an effect on the tumor microenvironment by blocking FGFR and PDGFR beta
Lenvatinib has been investigated in thyroid cancer and hepatocellular carcinoma phase III trials and in other malignancies showing high rates of activity
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 andor metastatic ACC
Recently two whole genome sequencing of ACC tumornormal pairs have found mutations in genes involved in the FGFIGFPI3K pathway up to 30 of the cases corroborating the hypothesis that this subset might benefit from agents targeting this pathway Dovitinib a small molecule that inhibits FGFR is currently under investigation Preliminary results indicate that the drug produces objective partial responses and prolonged tumor stabilization in patients with progressive ACCs Lenvatinib has a stronger antiangiogenic effect compared to sorafenib and axitinib and has also a higher potency with regard to inhibition of FGFR-1 offering a potential opportunity to block one of the well known mechanisms of resistance to VEGFVEGFR inhibitors Lenvatinib also has a direct oncogenic effect of controlling tumor cell proliferation by inhibiting RET c-KIT and PDGFR beta as well as an effect on the tumor microenvironment by blocking FGFR and PDGFR beta
Lenvatinib has been investigated in thyroid cancer and hepatocellular carcinoma phase III trials and in other malignancies showing high rates of activity
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 andor metastatic ACC
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None