Ignite Creation Date:
2025-12-24 @ 4:40 PM
Ignite Modification Date:
2025-12-31 @ 5:07 AM
Study NCT ID:
NCT04739566
Status:
WITHDRAWN
Last Update Posted:
2024-03-25
First Post:
2021-01-29
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Dabrafenib and Trametinib Combination as a Neoadjuvant Strategy in BRAF-positive Anaplastic Thyroid Cancer
Sponsor:
Saint Petersburg State University, Russia
Organization:
Study Overview
Official Title:
Dabrafenib and Trametinib Combination as a Neoadjuvant Strategy in BRAF-positive Anaplastic Thyroid Cancer (ANAPLAST-NEO)
Status:
WITHDRAWN
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Lack of funding
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ANAPLAST-NEO
Brief Summary:
The aim of the study was to evaluate the effectiveness of combination therapy with dabrafenib and trametinib (anti-BRAF and anti-MEK inhibitors) in the neoadjuvant treatment of BRAF-positive anaplastic thyroid cancer. The prognosis in patients with ATC is poor due to the rapid and invasive tumor growth and the rapid development of metastases.
Dabrafenib is an antineoplastic agent, a selective RAF kinase inhibitor that competes with ATP. Oncogenic substitutions of the amino acid valine at position 600 (V600) BRAF lead to constitutive activation of the RAS / RAF / MEK / ERK pathway and stimulation of tumor cell growth.
Trametinib is a reversible, highly selective, allosteric inhibitor of the activation of mitogen-activated, extracellular signal-regulated kinases 1 (MEK1) and 2 (MEK2).
Dabrafenib and trametinib inhibit two kinases in the signaling pathway, BRAF, and MEK. The combination of the two drugs provides effective inhibition of proliferative signal conduction.
The investigators hypothesize that the combination treatment with these two drugs - dabrafenib and trametinib - can improve the response rate in the neoadjuvant mode in ATC without significant regimen-limiting toxicity and with better follow-up locoregional control.
Dabrafenib is an antineoplastic agent, a selective RAF kinase inhibitor that competes with ATP. Oncogenic substitutions of the amino acid valine at position 600 (V600) BRAF lead to constitutive activation of the RAS / RAF / MEK / ERK pathway and stimulation of tumor cell growth.
Trametinib is a reversible, highly selective, allosteric inhibitor of the activation of mitogen-activated, extracellular signal-regulated kinases 1 (MEK1) and 2 (MEK2).
Dabrafenib and trametinib inhibit two kinases in the signaling pathway, BRAF, and MEK. The combination of the two drugs provides effective inhibition of proliferative signal conduction.
The investigators hypothesize that the combination treatment with these two drugs - dabrafenib and trametinib - can improve the response rate in the neoadjuvant mode in ATC without significant regimen-limiting toxicity and with better follow-up locoregional control.
Detailed Description:
Primary endpoint
1. Objective Response Ratio (ORR) Evaluate the effectiveness of the combination of dabrafenib and trametinib using an objective response rate (ORR) for BRAF-mutated anaplastic thyroid cancer in neoadjuvant mode 7, 14, 28 days, 12, and 24 weeks after the start of treatment. Includes patients with a confirmed partial (PR) and complete response (CR) as the best response according to RECIST v 1.1.
2. Number of R0 resections after 3 months of neoadjuvant combination therapy with anti-BRAF and MEK inhibitors.
Comparison of the proportion of complete surgical resection (surgical resection R0 or R1) with historical controls of 5%. The R0 / R1 ratio will be determined by the proportion of patients who successfully undergo thyroidectomy with clear (R0) or microscopically positive (R1) resection margins.
Secondary endpoints
1. Safety Profile (Number / Severity of Serious Adverse Events, SAEs) Number of serious adverse events classified by severity as assessed by CTCAE v 5.0
2. Percentage of patients who received a complete response 3 months after the first dose of treatment.
3. Health-related quality of life Changes in health-related quality of life will be measured using the European Quality of Life Assessment Questionnaire (EQ-5D). The EQ-5D consists of a description and a health assessment. The health description consists of five dimensions (mobility, self-care, normal activities, pain/discomfort, and anxiety/depression), with each dimension identifying five levels of severity \[best (1) - worst (5)\]. Health assessment is assessed using a visual analog scale (\[worse (0) - better (100)\].
4. Progression-Free Survival (PFS) Median progression-free survival (mPFS) is defined as the time from the date of inclusion to the date of the first documented progression of disease or death from any cause, whichever occurs first. PFS will be determined based on the tumor score (RECIST criteria version 1.1).
5. Overall Survival (OS) Median overall survival (mOS) at 12, 24, 36, 48, and 60 months are calculated as the time from the date of inclusion to the date of death for any reason at the specific time points.
OUTLINE:
Patients receive dabrafenib orally (PO) twice daily (BID) and trametinib PO once daily (QD) for 3 months in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.
After completion of study treatment, patients are followed up every 3 months during years 1-2, every 6 months during years 3-4, and then annually thereafter.
1. Objective Response Ratio (ORR) Evaluate the effectiveness of the combination of dabrafenib and trametinib using an objective response rate (ORR) for BRAF-mutated anaplastic thyroid cancer in neoadjuvant mode 7, 14, 28 days, 12, and 24 weeks after the start of treatment. Includes patients with a confirmed partial (PR) and complete response (CR) as the best response according to RECIST v 1.1.
2. Number of R0 resections after 3 months of neoadjuvant combination therapy with anti-BRAF and MEK inhibitors.
Comparison of the proportion of complete surgical resection (surgical resection R0 or R1) with historical controls of 5%. The R0 / R1 ratio will be determined by the proportion of patients who successfully undergo thyroidectomy with clear (R0) or microscopically positive (R1) resection margins.
Secondary endpoints
1. Safety Profile (Number / Severity of Serious Adverse Events, SAEs) Number of serious adverse events classified by severity as assessed by CTCAE v 5.0
2. Percentage of patients who received a complete response 3 months after the first dose of treatment.
3. Health-related quality of life Changes in health-related quality of life will be measured using the European Quality of Life Assessment Questionnaire (EQ-5D). The EQ-5D consists of a description and a health assessment. The health description consists of five dimensions (mobility, self-care, normal activities, pain/discomfort, and anxiety/depression), with each dimension identifying five levels of severity \[best (1) - worst (5)\]. Health assessment is assessed using a visual analog scale (\[worse (0) - better (100)\].
4. Progression-Free Survival (PFS) Median progression-free survival (mPFS) is defined as the time from the date of inclusion to the date of the first documented progression of disease or death from any cause, whichever occurs first. PFS will be determined based on the tumor score (RECIST criteria version 1.1).
5. Overall Survival (OS) Median overall survival (mOS) at 12, 24, 36, 48, and 60 months are calculated as the time from the date of inclusion to the date of death for any reason at the specific time points.
OUTLINE:
Patients receive dabrafenib orally (PO) twice daily (BID) and trametinib PO once daily (QD) for 3 months in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.
After completion of study treatment, patients are followed up every 3 months during years 1-2, every 6 months during years 3-4, and then annually thereafter.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: