A Phase I/II Trial of Dabrafenib, Trametinib and Metformin Administered to Unresectable Stage IIIC and Stage IV BRAF V600E + Melanoma Patients
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Clinical Response Rate
研究概览
简要总结
The main purpose is to evaluate the clinical response, safety and survival of the FDA approved drugs Dabrafenib, Trametinib in combination with Metformin. Investigators hypothesize that the combination of an FDA approved non toxic dose of oral Metformin with the B-Raf inhibitor, Dabrafenib and the MEK inhibitor, Trametinib will yield little toxicity and improve clinical outcomes in terms of objective response rates and survival in metastatic melanoma patients.
详细描述
The study will be a single-arm, single center, uncontrolled phase I/II trial to estimate the safety of the combined treatments and then estimate the efficacy in terms of objective response rate in patients with stage IIIC and Stage IV melanoma treated with dabrafenib/trametinib and metformin.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients > 18 years of age
- •Patients with histologically confirmed BRAFV600E melanoma (Stage IIIC or
- •Stage IV, American Joint Commission on Cancer)
- •Eastern Cooperative Oncology Group Performance Status of 0 to 2
- •Life expectancy > 3 months
- •At least 1 site of radiographically measurable disease by RECIST 1.1
- •Adequate hematologic, renal, and liver function as defined by laboratory values performed within 42 days prior to initiation of dosing:
- •Absolute neutrophil count > 1.0 x 10⁹/L
- •Platelet count > 50 x 10⁹/L
- •Hemoglobin > 8 g/dL
- •Serum creatinine < 2 x upper limit of normal
- •Total serum bilirubin < 3 x ULN
- •Serum aspartate transaminase or serum alanine transaminase < 3 x ULN, and < 4 x ULN if liver metastases are present
- •Fertile males should use an effective method of contraception during treatment and for at least 3 months after completion of treatment, as directed by their physician
- •Pre-menopausal females and females < 2 years after the onset of menopause should have a negative pregnancy test at Screening. Pre-menopausal females must agree to use an acceptable method of birth control from the time of the negative pregnancy test up to 90 days after the last dose of the study drug
- •Females of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for > 1 year
- •Before study entry, written informed consent must be obtained from the patient prior to performing any study related procedures
排除标准
- •Prior treatment with Vemurafenib or Dabrafenib
- •Known hypersensitivity to Metformin or any of its components
- •Received radiotherapy for non CNS disease within the 2 weeks prior to commencing study treatment or have not recovered from side effects of all radiation related toxicities to Grade < 1, except for alopecia
- •Pregnant, breast feeding, or refusing double barrier contraception, oral contraceptives, or avoidance of pregnancy measures
- •Have any other uncontrolled infection or medical condition that could interfere with the conduct of the study
研究组 & 干预措施
Dabrafenib, Trametinib and Metformin
Dabrafenib 150 mg PO BID until progression or unacceptable toxicity. Trametinib 2 mg PO QD until progression or unacceptable toxicity. Metformin 500 mg PO BID x 2 weeks, then 850 mg PO BID until progression or unacceptable toxicity.
干预措施: Metformin (Drug)
Dabrafenib, Trametinib and Metformin
Dabrafenib 150 mg PO BID until progression or unacceptable toxicity. Trametinib 2 mg PO QD until progression or unacceptable toxicity. Metformin 500 mg PO BID x 2 weeks, then 850 mg PO BID until progression or unacceptable toxicity.
干预措施: Dabrafenib (Drug)
Dabrafenib, Trametinib and Metformin
Dabrafenib 150 mg PO BID until progression or unacceptable toxicity. Trametinib 2 mg PO QD until progression or unacceptable toxicity. Metformin 500 mg PO BID x 2 weeks, then 850 mg PO BID until progression or unacceptable toxicity.
干预措施: Trametinib (Drug)
结局指标
主要结局
Clinical Response Rate
时间窗: 6 years
Phase II will study the efficacy of the drugs enrolling 20 patients during stage I with an upper limit of 39 for the 2nd stage.
Observation of two CTCAE drug related grade 4 toxicities in six patients.
时间窗: Duration of phase I portion, approxiately 6 months
During phase I, six patients will be enrolled and monitored for toxicities. If drug related deaths occur or more than two drug related CTCAE grade 4 toxicities occur the trial will be suspended. Phase II will estimate the efficacy of the drugs, enrolling 20 patients during stage 1 with an upper limit of 39 for the 2nd stage.
次要结局
- To explore the effect of other covariates on overall survival(3 years)
- To estimate the overall survival rates.(Approximately 3 years)
研究者
Jason Chesney
Director, James Graham Brown Cancer Center
University of Louisville