View clinical trials related to Thyroid Carcinoma, Anaplastic.
Filter by:The aim of the study was to evaluate the effectiveness of combination therapy with dabrafenib and trametinib (anti-BRAF and anti-MEK inhibitors) in the neoadjuvant treatment of BRAF-positive anaplastic thyroid cancer. The prognosis in patients with ATC is poor due to the rapid and invasive tumor growth and the rapid development of metastases. Dabrafenib is an antineoplastic agent, a selective RAF kinase inhibitor that competes with ATP. Oncogenic substitutions of the amino acid valine at position 600 (V600) BRAF lead to constitutive activation of the RAS / RAF / MEK / ERK pathway and stimulation of tumor cell growth. Trametinib is a reversible, highly selective, allosteric inhibitor of the activation of mitogen-activated, extracellular signal-regulated kinases 1 (MEK1) and 2 (MEK2). Dabrafenib and trametinib inhibit two kinases in the signaling pathway, BRAF, and MEK. The combination of the two drugs provides effective inhibition of proliferative signal conduction. The investigators hypothesize that the combination treatment with these two drugs - dabrafenib and trametinib - can improve the response rate in the neoadjuvant mode in ATC without significant regimen-limiting toxicity and with better follow-up locoregional control.
The aim of the study is to evaluate the efficacy of the combination of lenvatinib with pembrolizumab, and to establish a safe and effective systemic treatment regimen for patients with metastatic anaplastic thyroid cancer (ATC) / poorly differentiated thyroid cancer (PDTC). Lenvatinib is an anti-angiogenic and antiproliferative drug used in differentiated thyroid cancer. It blocks proliferative genes such as RET and PDGFR and further inhibits major proliferation pathways such as VEGF receptor signaling and FGFR1-4. Pembrolizumab is an immune checkpoint inhibitor that targets PD-1 located on lymphocytes. The response to pembrolizumab treatment is associated, among other things, with increased expression of PD-L1, as well as with the frequency of somatic mutations in the respective tumors. Patients with ATC / PDTC show high expression of PD-L1.
This is an, open-label, protocol designed to evaluate the activity of targeted therapy in anaplastic/undifferentiated thyroid cancer. Arm A will evaluate ATC/UTC with mutations or rearrangements detected in the ALK gene. There is no effective treatment for anaplastic thyroid cancer in the locally recurrent or metastatic setting. Ceritinib will be administered to the patient until disease progression by RECIST 1.1, unacceptable toxicity, withdrawal of consent, or discontinuation of the trial for any other reason. The primary focus of this arm of the protocol is identifying ceritinib's activity in anaplastic or undifferentiated thyroid cancer patients. Those patients with mutations identified in their ALK gene by sequencing their tumor samples, or with the established ALK abnormalities will be treated with ALK-inhibitors. These include the Ventana assay and Vysis FISH probe, and patients with tumors positive by this assay will also be considered eligible for therapy on the trial. Therapeutic Portion: ARM A: ALK Abnormality IND Ceritinib 750 mg orally daily on Day 1 Continue q4 weeks x 2 cycles Primary Endpoint: The development of progression; new recurrence or distant metastasis, as well as enlargement of an existing metastasis on radiographic imaging. Secondary Endpoints: 1. Overall response rate for patients treated with ceritinib as part of the study. 2. Death of study participant due to any cause.