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

NCT06079333 | Recruiting Phase 2 DMC

• 1 other identifier: NEOAC
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Anaplastic Thyroid Cancer

Outcome Measures

Primary Outcomes (1)

• primary endpoint of the study will be R0 resection rate (efficacy).

  primary endpoint of the study will be R0 resection rate (efficacy).

  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)

  during 1 year of treatment with braf/mek-inhibition

• 30-day postoperative surgical complications

  within 30 days after surgery

• Histopathological response after neo-adjuvant treatment

  6-12 weeks neo-adjuvant braf/mek-inhibition

• Locoregional-free survival

  at 2 years

• Distant metastasis-free survival

  at 2 years

Study Arms (1)

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.

Drug: dabrafenib/trametinib

Interventions

dabrafenib/trametinib DRUG

braf/mek-inhibition

neo-adjuvant and adjuvant braf/mek-inhibition

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Novartis: collaborator

Study Sites (1)

Ellen Kapiteijn

Leiden, South Holland, 2300RC, Netherlands

RECRUITING

MeSH Terms

Conditions

Thyroid Carcinoma, Anaplastic

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Ellen Kapiteijn, MD, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ellen Kapiteijn, MD, PhD

CONTACT

0031-71-5263486; h.w.kapiteijn@lumc.nl

Saskia Luelmo, MD

CONTACT

0031-71-5263464; S.A.C.Luelmo@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: prospective, non-randomized, single center, open-label phase II study

Study Record Dates

• First Submitted: June 29, 2023
• First Posted: October 12, 2023
• Study Start: January 1, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: October 12, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)