Targeted therapy for BRAF-mutated anaplastic thyroid cancer

NEO- and Adjuvant Targeted Therapy in Braf-mutated Anaplastic Cancer of the Thyroid (NEO-ATACT Study)

This study is testing a new treatment using two targeted drugs to see if it helps patients with a specific type of thyroid cancer have better surgery outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Leiden University Medical Center (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, trametinib
• Locations: 1 site (Leiden, South Holland)
• Trial ID: NCT06079333 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of neo-adjuvant and adjuvant treatment using dabrafenib and trametinib in patients with BRAF-mutated anaplastic thyroid cancer (ATC). The approach aims to improve surgical outcomes by increasing the likelihood of achieving clear surgical margins after treatment. Patients will receive targeted therapy before surgery to address micro/macrometastases and potentially enhance their eligibility for complete tumor resection. The study is conducted at a single center and focuses on a specific genetic mutation associated with ATC.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with histologically confirmed BRAF-mutated anaplastic thyroid cancer and no distant metastases.

Not a fit: Patients with distant metastases or those who have received prior systemic treatment for cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve surgical outcomes and survival rates for patients with BRAF-mutated anaplastic thyroid cancer.

How similar studies have performed: Previous studies have shown that targeted BRAF/MEK inhibition can benefit patients with BRAF-mutated cancers, suggesting potential success for this approach in ATC.

Eligibility criteria

Inclusion Criteria:

1. Informed consent.
2. Age over 18 years old.
3. World Health Organization (WHO) Performance Status 0 or I.
4. Histologically confirmed ATC (centrally reviewed).
5. Confirmed presence of BRAFV600E/K mutation in primary tumor tissue.
6. No distant metastases (M0).
7. Free or secured airway.
8. Able to swallow pills.
9. Patients must have undergone complete disease staging including: PET-CT scan and CT-neck/thorax/abdomen.
10. No prior anticancer systemic treatment (including chemotherapy, immunotherapy, oncolytic viral therapy, other systemic therapies).
11. No prior radiotherapy to site of interest.
12. 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.
13. Absence of additional severe and/or uncontrolled concurrent disease.

Exclusion Criteria:

1. No informed consent.
2. History of cancer within 2 years from diagnosis of ATC (exception: basal cell skin cancer, in situ carcinoma).
3. Poorly differentiated transformation of previous differentiated thyroid cancer.
4. Presence of distant metastases.
5. 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
6. 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.
7. Pregnancy or nursing.

Where this trial is running

Leiden, South Holland

• Ellen Kapiteijn — Leiden, South Holland, Netherlands (Recruiting)

Study contacts

• Principal investigator: Ellen Kapiteijn, MD, PhD — Leiden University Medical Center
• Study coordinator: Ellen Kapiteijn, MD, PhD

Conditions Anaplastic Thyroid Cancer