Lenvatinib in Recurrent and/or Metastatic Adenoid Cystic Carcinomas of the Salivary Glands: ACC-LEN14 (ACC-LEN14)
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|ClinicalTrials.gov Identifier: NCT02860936|
Recruitment Status : Completed
First Posted : August 10, 2016
Last Update Posted : September 2, 2019
|Condition or disease||Intervention/treatment||Phase|
|Adenoid Cystic Carcinomas of the Salivary Glands||Drug: Lenvatinib||Phase 2|
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 and/or 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 tumor/normal pairs have found mutations in genes involved in the FGF/IGF/PI3K 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 VEGF/VEGFR 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 and/or metastatic ACC.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study on Lenvatinib in Recurrent and/or Metastatic Adenoid Cystic Carcinomas of the Salivary Glands of the Upper Aerodigestive Tract|
|Study Start Date :||June 2015|
|Actual Primary Completion Date :||June 2019|
|Actual Study Completion Date :||June 2019|
24 mg of lenvatinib will be administered daily to patients until progression of disease or intolerable toxicity or other criteria for discontinuation is met.
Lenvatinib will be self orally administered at 24 mg daily, on a continuous basis in 4 week cycles until tumour progression, unacceptable toxicity or other criteria for discontinuation is met. Study drug should be taken at approximately the same time each morning.
Other Name: Lenvima
- Objective response rate (CR+PR) [ Time Frame: 2 years and 5 months ]Objective response rate (CR+PR) will be evaluated according to RECIST response evaluation criteria 1.1 at any subsequent re-evaluation
- Progression free survival [ Time Frame: 2 years and 5 months ]PFS according to RECIST criteria 1.1
- Overall survival [ Time Frame: 2 years and 5 months ]After study drug treatment ends, patients will be contacted each 6 months to determine survival
- Safety and toxicity profile of lenvatinib (according to CTCAE v 4.0) [ Time Frame: 2 years and 5 months ]Incidence of adverse events (AEs), will be graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0, laboratory values, physical examinations, vital signs.
- Duration of response [ Time Frame: 2 years and 5 months ]The duration of response will be evaluated to assess the duration of activity of lenvatinib (CR+PR+SD)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02860936
|Fondazione IRCCS Istituto Nazionale dei Tumori|
|Milan, Italy, 20133|
|Principal Investigator:||Lisa Licitra||Fondazione IRCCS Istituto Nazionale dei Tumori, Milano|