NCT03975231招募中1 期
A Phase I Trial of Concurrent Intensity Modulated Radiation Therapy (IMRT) and Dabrafenib/Trametinib in BRAF Mutated Anaplastic Thyroid Cancer
City of Hope Medical Center3 个研究点 分布在 1 个国家目标入组 6 人开始时间: 2020年9月14日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 6
- 试验地点
- 3
- 主要终点
- Maximum tolerated dose of combination therapy of dabrafenib and trametinib administered concurrently with intensity-modulated radiation therapy (IMRT)
研究概览
简要总结
This trial studies how well dabrafenib, trametinib, and intensity modulated radiation therapy (IMRT) work together in treating patients with BRAF mutated anaplastic thyroid cancer. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Giving dabrafenib, trametinib, and IMRT together may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability (maximum tolerated dose [MTD]) of concurrent intensity modulated radiation therapy (IMRT) and BRAF-MEK inhibitors dabrafenib and trametinib in patients with BRAF-mutated anaplastic thyroid cancer.
SECONDARY OBJECTIVES:
I. To assess overall objective response rate, time to progression of local recurrence, progression free survival and overall survival.
II. To assess pharmacokinetics during concurrent IMRT and dabrafenib plus trametinib therapy.
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
- •Pathologic (histologic or cytologic) diagnosis of anaplastic thyroid cancer (a diagnosis that is noted to be ?consistent with anaplastic thyroid cancer? with the presence of a thyroid mass is acceptable; pathology showing additional types of thyroid cancer is allowed)
- •Note: Tissue collection for central review is mandatory, but central review is not required for eligibility. Due to the aggressiveness of this disease, treatment will be started prior to central review.
- •Presence of BRAF mutation (V600E or V600K) in tumor tissue.
- •Eastern Cooperative Oncology Group (ECOG) performance status <
- •Absolute neutrophil count > 1,000/mcL.
- •Hemoglobin >= 9.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable).
- •Platelets > 75,000/mcL.
- •Total bilirubin < 1.5 x institutional upper limit of normal (unless due to Gilbert?s disease).
- •Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional upper limit of normal.
- •Serum creatinine < 1.5 x institutional upper limit of normal.
- •Female patients of childbearing potential are required to have a negative serum pregnancy test within 14 days prior to the first dose of study medication.
- •Females are required to use an effective method of contraception from the time of negative serum pregnancy test, throughout the study duration, and for 4 months after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to study enrollment, for the duration of study participation, and for 16 weeks after completion of the last dose of study drug.
- •Specific contraception requirements for females: Female subjects of childbearing potential must not become pregnant and are required to be sexually inactive by abstinence or use contraceptive methods with a failure rate of < 1%. Sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception. Contraceptive methods with a failure rate of < 1% include the following:
- •Intrauterine device (IUD) or intrauterine system (IUS) that meets the < 1% failure rate as stated in the product label,
- •Male partner sterilization (vasectomy with documentation of Azoospermia) prior to the female subject's entry into the study, and this male is patient?s sole sexual partner. For this definition, ?documented? refers to the outcome of the investigator's/qualified physician designee?s medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject?s medical records.
- •Double barrier method: condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam, gel, film, cream, suppository) These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring subjects understand how to properly use these methods of contraception.
- •Specific contraception requirements for males: To prevent pregnancy in a female partner or to prevent exposure of any partner to the investigational product from a male subject?s semen, male subjects must use one of the following contraceptive methods during the study and for a total of 16 weeks following the last dose of study drug (based upon the lifecycle of sperm):
- •Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject for 14 days prior to first dose of study drug, through the dosing period, and for at least 16 weeks after the last dose of study drug. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- •Condom (during non-vaginal intercourse with any partner - male or female) OR
- •Condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) (during sexual intercourse with a female).
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Patients with resectable stage IVA anaplastic thyroid cancer who are candidates for surgery and wish to proceed with surgery.
- •Patients who have had external beam radiotherapy to neck or chest for cancer that would result in overlap of radiation therapy fields.
- •Patients who have had cytotoxic chemotherapy, stereotactic brain radiation or external beam radiation within 2 weeks prior to study treatment initiation.
- •Patients who have had oral multikinase inhibitors within 1 week prior to study treatment initiation.
- •Patients that have not recovered from adverse events related to prior therapy for cancer to Common Terminology Criteria for Adverse Events (CTCAE) 4.03 grade 2 or less except for alopecia.
- •Patients previously treated with potent BRAF inhibitor or MEK inhibitor. Previous treatment with sorafenib is permitted.
- •Patients that are receiving any other investigational agent.
- •Patients that are currently taking any prohibitive medication.
- •Patients with a history of other active malignancy requiring cancer treatment.
- •Patients with uncontrolled brain metastases. Patients who are on a stable dose of corticosteroids for more than 1 week or off corticosteroids for 2 weeks prior to study enrollment can be enrolled. Enzyme-inducing anti-epileptic drugs are not permitted.
- •Patients with a known history of retinal vein occlusion (RVO), central serous retinopathy (CSR), uncontrolled glaucoma or ocular hypertension.
- •Patients with class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- •Corrected QT (QTc) interval greater than or equal to 480 msecs (>= 500 msec for subjects with Bundle Branch Block).
- •Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous (IV) antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant women and nursing women are excluded from this study because dabrafenib has the potential for teratogenic or abortifacient effects. In embroyfetal developmental studies in rats, developmental toxicities including reduced fetal body weight, embryo-lethality, cardiac ventricular septal defect malformations, delayed skeletal development and variation in thymic shape have been observed.
- •Known human immunodeficiency virus (HIV)-positive patients or those on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with study drugs.
研究组 & 干预措施
Treatment (dabrafenib, trametinib, IMRT)
Experimental
See Detailed Description
干预措施: Dabrafenib (Drug)
Treatment (dabrafenib, trametinib, IMRT)
Experimental
See Detailed Description
干预措施: Intensity-Modulated Radiation Therapy (Radiation)
Treatment (dabrafenib, trametinib, IMRT)
Experimental
See Detailed Description
干预措施: Trametinib (Drug)
结局指标
主要结局
Maximum tolerated dose of combination therapy of dabrafenib and trametinib administered concurrently with intensity-modulated radiation therapy (IMRT)
时间窗: 1 year
次要结局
- Objective response rate(1 year)
- Time to progression for local disease recurrence(1 year)
- Overall survival(From the start date of the treatment to the date of death, assessed up to 1 year)
- Progression free survival(Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year)
研究者
研究点 (3)
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