Anaplastic Thyroid CancerPhase 2NEO-ATACTNCT06079333
NEO- and Adjuvant Targeted Therapy in Braf-mutated Anaplastic Cancer of the Thyroid (NEO-ATACT Study)
A Phase 2 study testing dabrafenib/trametinib in people with Anaplastic Thyroid Cancer, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anaplastic Thyroid Cancer
- What is being tested?
- dabrafenib/trametinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Jan 2023to 1 Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent.
- Age over 18 years old.
- World Health Organization (WHO) Performance Status 0 or I.
- Histologically confirmed ATC (centrally reviewed).
- Confirmed presence of BRAFV600E/K mutation in primary tumor tissue.
- No distant metastases (M0).
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- Free or secured airway.
- Able to swallow pills.
- Patients must have undergone complete disease staging including: PET-CT scan and CT-neck/thorax/abdomen.
- No prior anticancer systemic treatment (including chemotherapy, immunotherapy, oncolytic viral therapy, other systemic therapies).
- No prior radiotherapy to site of interest.
- Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥ 1.0x109/L, Platelets ≥ 100 x109/L, Hemoglobin ≥ 6.5 mmol/L, AST ≤ 2.5 x ULN, ALT ≤ 2.5 x ULN, Total bilirubin ≤ 1.5 X ULN, INR and PTT in normal range, LDH < 2xULN. Serum creatinine ≤ 1.5 × ULN; or calculated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula; or estimated glomerular filtration rate > 50 mL/min/1.73m2.
- Absence of additional severe and/or uncontrolled concurrent disease.
Who cannot join
- No informed consent.
- History of cancer within 2 years from diagnosis of ATC (exception: basal cell skin cancer, in situ carcinoma).
- Poorly differentiated transformation of previous differentiated thyroid cancer.
- Presence of distant metastases.
- Underlying medical conditions that, in the Investigator's opinion, will make the administration of study treatment hazardous or obscure the interpretation of toxicity determination or adverse events
- History of congestive heart failure, active cardiac conditions, including unstable coronary syndromes, significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia.
- Pregnancy or nursing.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Ellen Kapiteijn
Leiden, South Holland, 2300RC
Ellen Kapiteijn, MD, PhD, +31715263486, h.w.kapiteijn@lumc.nl
About this study
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.
Read the detailed description
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.
- Conditions
- Anaplastic Thyroid Cancer
- Being tested
- dabrafenib/trametinib
- Medical subject headings
- Thyroid Carcinoma, Anaplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dabrafenib/trametinibDrug
braf/mek-inhibition
| Study group | Role | What they receive |
|---|---|---|
| neo-adjuvant and adjuvant braf/mek-inhibition | Experimental | 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. Receives: Drug: dabrafenib/trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
primary endpoint of the study will be R0 resection rate (efficacy).
primary endpoint of the study will be R0 resection rate (efficacy).
Measured: after 6-12 weeks braf/mek-inhibition
Secondary outcomes (6)
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
Measured: during 1 year of treatment with braf/mek-inhibition
30-day postoperative surgical complications
30-day postoperative surgical complications (within 30 days after surgery)
Measured: 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)
Measured: 6-12 weeks neo-adjuvant braf/mek-inhibition
Locoregional-free survival
Locoregional-free survival
Measured: at 2 years
Distant metastasis-free survival
Distant metastasis-free survival
Measured: at 2 years
Overall survival
Overall survival
Measured: at 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2023
- Study start1 Jan 2023
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anaplastic Thyroid CancerStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- prospective, non-randomized, single center, open-label phase II study
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Principal investigator, HW Kapiteijn, Leiden University Medical Center
- Investigators
- Ellen Kapiteijn, MD, PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06079333
- Sponsor's protocol ID
- NEOAC
- Acronym
- NEO-ATACT
- Status last verified
- Oct 2023
- First submitted
- 29 Jun 2023
- Last updated
- 12 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NEO- and Adjuvant Targeted Therapy in Braf-mutated Anaplastic Cancer of the Thyroid (NEO-ATACT Study)
- ClinicalTrials.gov ID
- NCT06079333
- Acronym / sponsor ID
- NEO-ATACT / NEOAC
- Conditions
- Anaplastic Thyroid Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 12 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- prospective, non-randomized, single center, open-label phase II study
| Arm | Type | Receives |
|---|---|---|
| neo-adjuvant and adjuvant braf/mek-inhibition | Experimental | Drug: dabrafenib/trametinibParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Informed consent.
- Age over 18 years old.
- World Health Organization (WHO) Performance Status 0 or I.
- Histologically confirmed ATC (centrally reviewed).
- Confirmed presence of BRAFV600E/K mutation in primary tumor tissue.
Key exclusion criteria (7 listed)
- No informed consent.
- History of cancer within 2 years from diagnosis of ATC (exception: basal cell skin cancer, in situ carcinoma).
- Poorly differentiated transformation of previous differentiated thyroid cancer.
- Presence of distant metastases.
- Underlying medical conditions that, in the Investigator's opinion, will make the administration of study treatment hazardous or obscure the interpretation of toxicity determination or adverse events
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dabrafenib/trametinibbraf/mek-inhibition | Drug | neo-adjuvant and adjuvant braf/mek-inhibition |
Primary outcome
primary endpoint of the study will be R0 resection rate (efficacy).
Time frame: after 6-12 weeks braf/mek-inhibition
primary endpoint of the study will be R0 resection rate (efficacy).
6 secondary outcomes
Neo-adjuvant and adjuvant treatment related toxicity of dabrafenib/trametinib (according to CTCAE v. 5.0)
Time frame: during 1 year of treatment with braf/mek-inhibition
30-day postoperative surgical complications
Time frame: within 30 days after surgery
Histopathological response after neo-adjuvant treatment
Time frame: 6-12 weeks neo-adjuvant braf/mek-inhibition
Locoregional-free survival
Time frame: at 2 years
Distant metastasis-free survival
Time frame: at 2 years
Overall survival
Time frame: at 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ellen Kapiteijn, MD, PhD principal investigator
Leiden University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing dabrafenib/trametinib in people with Anaplastic Thyroid Cancer, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ellen Kapiteijn, MD, PhD (0031-71-5263486, h.w.kapiteijn@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
primary endpoint of the study will be R0 resection rate (efficacy). (time frame: after 6-12 weeks braf/mek-inhibition). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2023.