A Phase 2 interventional study of dabrafenib/trametinib in Anaplastic Thyroid Cancer, sponsored by Leiden University Medical Center. Recruiting at 1 site in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-10-12.
Sponsored by Leiden University Medical Center · Phase 2, Interventional, and Treatment
Anaplastic thyroid cancer (ATC) is an almost invariable lethal cancer in humans.
Most patients present with a rapid progressive mass in the neck with progressive complaints like dyspnoea, dysphagia or pain. The risk of suffocation is the main reason for rapid surgical intervention, but we know from literature that an oncological resection with clear margins is seldomly achieved. Some patients deteriorate that fast after surgery that radiation therapy and/or chemotherapy is not feasible anymore. Patients with BRAF-mutated ATC already have shown to benefit from targeted BRAF/MEK inhibition. This study aims to increase the number of patients that undergo a successful R0 tumor resection after neo-adjuvant BRAF/MEK inhibitor treatment.
Unmet need ATC is a very serious condition and is, apart from a few exclusive cases, always lethal. Many patients suffer uncontrollable loco-regional disease with even so uncontrollable complaints of airway obstruction, oesophagus obstruction, pain and neck movement impairment. One of the only shown beneficial treatment is complete surgical resection with clear surgical margins combined with radiotherapy and systemic treatment. However, in less than 10-15% of the patients the pathologist reports clear surgical margins. Thereby it is noticeable that surgery often results in serious morbidity, due to an esophagectomy, laryngectomy or trachea resection all accompanied by an extensive reconstruction. All of these come with serious morbidity and seldomly lead to clear margins and better outcome.
Proposed solution A single center, phase II study for the evaluation of safety and efficacy of neo-adjuvant and adjuvant dabrafenib/trametinib treatment in BRAF mutated ATC patients. By introducing neo-adjuvant treatment the hypothesis is that better selection is done for patients who are eligible for complete surgery and that surgery results more often in clear surgical margins after neo-adjuvant treatment. Second benefit of treating patients with combined loco-regional and systemic agents before surgery is that micro/macrometastases (being there in at least 30% of the patients at diagnosis) are already being treated directly after diagnosis. Lastly, adjuvant treatment with dabrafenib/trametinib will hopefully result in reduction of local and distant recurrences after surgery.
802 studies on the registry are indexed under Thyroid Neoplasms; 216 are open to participants now.
This study's planned enrollment of 20 is below the median of 51 across 507 interventional studies indexed under Thyroid Neoplasms.
Browse Thyroid Neoplasms studies →Leiden University Medical Center is the lead sponsor of 326 studies on the registry; 106 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants will undergo neo-adjuvant treatment with dabrafenib/trametinib. After 6 weeks of BRAF/MEK inhibitors, participants will undergo an evaluation of resectability. If the tumor is resectable, patients undergo tumor resection. If not resectable, neo-adjuvant treatment continues for another 6 weeks followed by a new evaluation. All resected patients receive adjuvant dabrafenib/trametinib up to a total treatment duration of 52 weeks. If resection is not possible, patients will continue on dabrafenib/trametinib.
Drug: dabrafenib/trametinib
braf/mek-inhibition
primary endpoint of the study will be R0 resection rate (efficacy).
primary endpoint of the study will be R0 resection rate (efficacy).
Time frame: after 6-12 weeks braf/mek-inhibition
Neo-adjuvant and adjuvant treatment related toxicity of dabrafenib/trametinib (according to CTCAE v. 5.0)
Neo-adjuvant and adjuvant treatment related toxicity of dabrafenib/trametinib (according to CTCAE v. 5.0) during 1 year of treatment with braf/mek-inhibition
Time frame: during 1 year of treatment with braf/mek-inhibition
30-day postoperative surgical complications
30-day postoperative surgical complications (within 30 days after surgery)
Time frame: within 30 days after surgery
Histopathological response after neo-adjuvant treatment
Histopathological response after neo-adjuvant treatment: complete response (\<10% tumor cells), partial response (between more than 10% and up to 50% tumor cells), or no response (still more than 50% tumor cells)
Time frame: 6-12 weeks neo-adjuvant braf/mek-inhibition
Locoregional-free survival
Locoregional-free survival
Time frame: at 2 years
Distant metastasis-free survival
Distant metastasis-free survival
Time frame: at 2 years
Overall survival
Overall survival
Time frame: at 2 years
Plan to share: No
No publications or documents are linked to this record.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Leiden University Medical Center