Study of the Rechallenge Concept in Patients With BRAF-positive Anaplastic Thyroid Cancer After Progression on Anti-BRAF Therapy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Progression-Free Survival
研究概览
简要总结
This pilot phase 2 study evaluates the effectiveness and safety of the Rechallenge concept in patients with BRAF-positive anaplastic thyroid cancer after progression on anti-BRAF therapy. Patients with BRAF-positive anaplastic thyroid cancer who were previously treated with dabrafenib and trametinib (with a clinical or objective response at the start of treatment) and later with tumor progression during anti-BRAF therapy and subsequent lines of chemotherapy are scheduled to undergo targeted therapy (repeated administration of dabrafenib and trametinib in standard doses) and evaluate the outcomes according to the primary and secondary endpoints.
详细描述
The aim of the study was to demonstrate the efficacy and safety of the rechallenge concept in patients with BRAF-positive anaplastic thyroid cancer after progression on anti-BRAF therapy.
Scientific hypothesis: rechallenge in patients with BRAF-positive anaplastic thyroid cancer after progression on anti-BRAF therapy is effective and safe.
Trial design, materials and methods: this study is a pilot phase 2 study. This study is prospective and open-label.
Patients with BRAF-positive anaplastic thyroid cancer who were previously treated with dabrafenib and trametinib (with a clinical or objective response at the start of treatment) and later with tumor progression during anti-BRAF treatment with the transition to at least one line of chemotherapy (treatment with taxane-containing regimens is mandatory) followed by progression on it. Patients who meet the criteria and with no initial resistance to anti-BRAF therapy are scheduled to undergo targeted therapy (repeated administration of dabrafenib and trametinib in standard doses) and evaluate outcomes according to primary and secondary endpoints.
The control will be carried out by monitoring the initial state in dynamics. Before starting investigational therapy, data will be recorded for each patient in an individual registration card.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •immunohistochemically verified anaplastic thyroid cancer;
- •presence of a mutation in the BRAF V600 gene;
- •documented progression during targeted therapy with dabrafenib + trametinib;
- •documented progression during at least one line of chemotherapy (use of taxane-containing chemotherapy is mandatory);
- •age ≥ 18 years;
- •ECOG performance status 0-2;
- •adequate function of internal organs and bone marrow;
- •ability to give written informed consent.
排除标准
- •primary resistance (absence of initial clinical and radiological response to therapy with dabrafenib and trametinib (response criteria - primary objective response according to RECIST 1.1 criteria and duration of response of at least 3 months);
- •absence of taxane-containing chemotherapy as second or third line;
- •contraindication to taking any of the study drugs (including severe toxicity that occurred during a previous dose, which led to discontinuation of treatment);
- •patients with unsatisfactory functional status (ECOG 3-4);
- •pregnancy and breastfeeding.
研究组 & 干预措施
Intervention group
Patients with BRAF-positive anaplastic thyroid cancer who were previously treated with dabrafenib and trametinib (with a clinical or objective response at the start of treatment) and later with tumor progression during anti-BRAF therapy with the transition to at least one line of chemotherapy (treatment with taxane-containing regimens is mandatory) followed by progression on it.
干预措施: Dabrafenib + Trametinib (Drug)
结局指标
主要结局
Progression-Free Survival
时间窗: 6-month, 1-year, 2-year
The time from the date of initiation of treatment to the radiological progression or death of the patient for any reason.
Objective response rate
时间窗: 10 days, then each month from date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
The proportion of participants with a partial or complete response to the therapy. It is determined according to the RECIST criteria.
Safety and Tolerability assessment (Incidence of Treatment-Emergent Adverse Events)
时间窗: Each visit (every 21 days) assessed up to 48 months
Safety assessment will be assessed on the basis of adverse events (according to CTCAE 5.0)
次要结局
- The assessment of conversion to resectability(Each month from date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first , assessed up to 48 months)
- Overall survival(6-month, 1-year, 2-year)
研究者
Ernest Dzhelialov
Oncologist
Saint Petersburg State University, Russia