Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Increased Radioiodine Uptake
研究概览
简要总结
Radioactive iodine therapy is often part of the standard treatment for Papillary Thyroid Carcinoma (PTC) patients. However, in many patients, tumors develop a resistance or no longer respond to radioactive iodine therapy (iodine-refractory). Several lines of evidence suggest that blocking the BRAF gene may help to re-sensitize the tumors to radioactive iodine. BRAF is a protein that plays a central role in the growth and survival of cancer cells in some types of PTC. The investigational drug GSK2118436 may work by blocking the BRAF protein in cancer cells lines and tumors that have a mutated BRAF gene.
In this research study, the investigators are looking to see if GSK2118436 can re-sensitize iodine-refractory PTC to radioactive iodine therapy. The investigators are also looking at the safety of adding GSK2118436 to radioactive iodine therapy.
详细描述
You will take GSK2118436 capsules by mouth for 28 straight days. If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine, you will take GSK2118436 for an additional 14 days (Days 29-42). You will be given a drug diary to record when you take GSK2118436. This diary will also contain instructions on how to take GSK2118436.
Prior to Day 1
- Optional fine needle aspirate (pre-treatment) Day 1
- Vital signs
- Routine blood tests (2 tablespoons)
- Research blood sample for Circulating Tumor Cells (CTCs). (4 teaspoons of blood)
- Optional research blood sample for CTCs 4-6 hours after the first dose of GSK2118436
Day 2:
- Optional research blood sample for CTCs 4-6 hours after the first dose of GSK2118436 Day 3-5: Research blood sample for CTCs Days 8 and 15
- Vital signs
- Routine blood tests (2 tablespoons)
- Research blood sample for CTCs. (4 teaspoons of blood)
- Optional fine needle aspirate (Day 15 only) Low Iodine Diet: You will begin a low iodine diet on Day 15, in preparation for Day 23 when you will receive radioactive iodine (131I). The study team will provide you with instructions on this diet. The low iodine diet will be continued until the whole body scan is complete. For those participants who will receive a therapeutic dose of radioactive iodine on Day 37, the low iodine diet will be continued until the Day 42 whole body scan is complete.
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
- •Histologically confirmed papillary thyroid carcinoma, including its variants, such as tall cell PTC or poorly differentiated thyroid carcinoma, that is metastatic or unresectable AND harbors a BRAF V600E mutation
- •Evaluable disease, as defined by at least one lesion that can be accurately measured in at least one dimension on CT scan or ultrasound, if present in the neck
- •Radioiodine-refractory disease
- •Life expectancy > 6 months
- •Able to swallow and retain oral medication
- •Normal organ and marrow function
排除标准
- •Pregnant or breastfeeding
- •Previous treatment with a specific BRAF or MEK inhibitor
- •Receiving any other study agents
- •Known brain metastases
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to GSK2118436, bovine TSH, mannitol or iodine
- •Active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs
- •History of known glucose-6-phosphate dehyrogenase (G6PD) deficiency
- •Corrected QT interval >/= 480 msecs; history of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks; Class II, III, or IV heart failure, abnormal cardiac valve morphology; or history of known cardiac arrhythmias
- •Taking herbal remedies
- •Subjects with significant symptoms from their thyroid cancer, or have a large burden of rapidly progressive iodine-refractory PTC who are in need of other systemic therapy, as judged by their treating physician
- •Uncontrolled current illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements
- •History of a different malignancy unless disease-free for at least 5 years and deemed to be at low risk for recurrence
- •HIV-positive on combination antiretroviral therapy
研究组 & 干预措施
GSK2118436
Intervention: GSK2118436 (dabrafenib) 150mg by mouth twice per day for 28 days, continued to day 42 if the Day 25 Iodine-131 scan shows new uptake. Patients with new Iodine-131 uptake on Day 25 who continue dabrafenib to day 42 receive a treatment dose (150 mCi) of Iodine-131 on Day 37.
干预措施: GSK2118436 (Drug)
结局指标
主要结局
Increased Radioiodine Uptake
时间窗: 25 days after start of Dabrafenib (GSK2118436)
Number of patients with radioiodine-refractory metastatic BRAF V600E-mutant PTC who have increased radioiodine uptake in their disease sites while on dabrafenib. Radioiodine uptake is assessed by whole body scan and areas of interest are identified by nuclear medicine physicians.
次要结局
- Safety Analysis as Number of Participants With Adverse Events(2 years)
- Clinical Benefit as Measured by Change in Tumor Size(2 years)
- Number of Participants Who Complete the Study With Minimal Delays and no Dose Reductions(2 years)
- Clinical Benefit as Measured by Change in Thyroglobulin Level(3 months after radioiodine therapy)
研究者
Lori J. Wirth, MD
Attending Physician
Massachusetts General Hospital