Neoadjuvant and Postoperative Treatment With Dabrafenib and Trametinib in BRAF Mutated Papillary Craniopharyngioma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Tumor response
研究概览
简要总结
Subjects with papillary craniopharyngioma harboring a BRAF mutation will be treated with a BRAF + MEK inhibitor (dabrafenib + trametinib) after informed consent. Study participants will be administered oral dabrafenib and trametinib until maximal tumor volume reduction assessed by MRI. Progression free survival, cognition, ophthalmologic status, hypothalamic status and quality of life will be assessed 1 year after initiation of study treatment
详细描述
Background. Papillary craniopharyngioma harbours a BRAF mutation in 90% of cases. Treatment with BRAF + MEK (mitogen activated protein kinase ) inhibitors (dabrafenib + trametinib) may prevent patients from undergoing surgery with a high risk of serious side effects, or provide an additional treatment option when further surgery is not advised.
Study intervention Subjects with newly diagnosed craniopharyngioma where radical surgery is not considered adequate or patients with recurrence of craniopharyngioma where further surgery is not considered possible without serious sequelae will be asked for informed consent Study participants are treated continuously with dabrafenib and trametinib orally, until maximal tumor shrinkage. Evaluation is done by MRI to measure tumor volume, as well as assessment of performance status, quality of life, cognition, ophthalmologic status, performance status and hypothalamic status.
Study type The study is a Phase II, single armed, open label and multicenter study Study drugs are Dabrafenib (Tafinlar) and trametinib (Mekinist) Primary outcome To evaluate tumor response in the form of reduced tumor volume on MRI in patients with papillary craniopharyngioma during treatment with dabrafenib and trametinib.
Secondary outcomes
To evaluate dabrafenib and trametinib treatment for the following aspects:
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 verified papillary craniopharyngioma.
- •BRAF mutated V600E (valine 600 glutamine), verified immunohistochemically and by molecular genetic analysis
- •Newly diagnosed tumor, or recurrence after previous surgery, where surgery is not considered to be able to be performed radically without the risk of serious or permanent sequelae.
- •Age over 18 years
- •Functional status according to ECOG (Eastern Cooperative Oncology Group performance status) 0-2
- •Adequate organ function:
- •neutrophils> 1.5 x 109 platelets> 100 x 109 creatinine <1.5 x ULN (upper limit of normal) or creatinine clearance <45 ml / min bilirubin <1.5 x ULN ASAT (aspartate aminotransferase) / ALAT (alanine aminotransferase) <2.5 x ULN
- •Ability to understand and give informed consent.
- •Previous cancer, which does not require current treatment is allowed.
- •The patient agrees to use an adequate method to avoid pregnancy.
排除标准
- •Ongoing treatment in another drug study or other experimental treatment.
- •Previous treatment with BRAF or MEK inhibitors.
- •Hypersensitivity to study drugs.
- •Ongoing treatment with non-authorized drugs, (strong inducers of CYP2C8 or CYP3A4). If the patient is on unauthorized drugs, they must be discontinued at least 14 days before inclusion.
- •Known cardiovascular disease where treatment with MEK inhibitors is considered inappropriate, eg severe heart failure, prolongation of QT time, uncontrolled arrhythmia, recent (<6 months) cardiac infarction, uncontrolled hypertension.
- •Active bleeding; intracranial hemorrhage last 4 weeks before inclusion.
- •Thromboembolic disease last 6 months and unstable anticoagulant treatment less than 4 weeks before inclusion.
- •Women who are pregnant or breastfeeding.
- •Previous central serous retinopathy or retinal vein occlusion.
- •Previous uveitis or iritis last 4 weeks before inclusion.
- •Surgery within the last 3 weeks.
- •For postoperative patients; radiation therapy within the last 3 months.
研究组 & 干预措施
Dabrafenib and trametinib
Dabrafenib 75 mg twice daily and trametinib 2 mg once daily
干预措施: Oral dabrafenib and trametinib (Drug)
结局指标
主要结局
Tumor response
时间窗: 1 month to 5 years (sliding timepoints)
To evaluate tumor response measured as maximally reduced tumor volume on MRI during treatment with dabrafenib and trametinib. Maximally reduced volume is defined as the time point where no further reduction of tumor volume can be observed
次要结局
- Response ratio(1 year after initiation of study treatment)
- Response duration(From time of study drug discontinuation to time of observed increased tumor volume assessed up to 1 year)
- Operability after neoadjuvant trial treatment(1 year after initiation of study treatment)
- Cognitive status after treatment(1 year)
- Progression-free survival 1 year(1 year)
- Progression-free survival 2 years(2 years)
- QOL after treatment(1 year)
- Hypothalamic status after treatment(1 year)
- Opthalmologic status after treatment(1 year)
研究者
Eva Marie Erfurth, MD, PhD
Professor
Skane University Hospital