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

• Status: Recruiting
• Trial end date: 2028-01-01
• Target enrollment: 0
• Participant gender: All

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. 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Leiden University Medical Center
• Collaborator: Novartis
• Treatments: Dabrafenib; Trametinib

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.