Pilot Study of Adaptive BRAF-MEK Inhibitor Therapy for Advanced BRAF Mutant Melanoma
试验速览
- 阶段
- 早期 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- 8 Week Completion Rate
研究概览
简要总结
This pilot early phase I trial studies how well encorafenib, binimetinib, and nivolumab work in treating patients with BRAF mutant stage IIIC-IV melanoma. Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with nivolumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving encorafenib, binimetinib, and nivolumab may kill more tumor cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Patients must be 18 years of age or above
- •Subjects must have cytologically or histologically-confirmed unresectable melanoma that harbors a BRAF V600E mutation determined by pyrosequencing assay or equivalent genotyping assay in a Clinical Laboratory Improvement Act (CLIA) certified laboratory, meeting one of the following American Joint Committee on Cancer (AJCC) (8th edition) staging criteria:
- •AJCC stage IV
- •AJCC stage IIIC or IIID with unresectable nodal/locoregional involvement
- •Subjects must have baseline plasma ctDNA >= 0.5 copy/ul at time of study enrollment
- •Hemoglobin >= 8.0 g/dL
- •Absolute neutrophil count >= 1,500/mcL
- •Platelets >= 75,000/mcL
- •Total bilirubin =< 2 institutional upper limit of normal (ULN), unless suspected Gilbert's syndrome
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional ULN (in participants with liver metastases =< 5 x ULN)
- •Creatinine =< 2.0 institutional ULN
- •Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- •Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for >= 1 year
- •Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. (NOTE: Patients must agree to not use hormonal contraceptives, as encorafenib can result in decreased concentration and loss of efficacy.)
- •Patients on non-biologic disease modifying agents (e.g. methotrexate) or patients on corticosteroids =< 10 mg prednisone daily or equivalent are permitted to enroll
- •Patients must not have had grade 3 or 4 immune-related adverse events on nivolumab that required more than 12 weeks of immune suppression with corticosteroids
- •No anti-PD-1/PD-L1 or BRAF/MEK inhibitor therapy in the metastatic setting is allowed; these treatments are allowed if given in neoaduvant or adjuvant setting > 24 weeks ago. Prior radiation therapy is permitted. All adverse events associated with prior systemic therapy or radiation therapy must have resolved to =< grade 1 prior to start of study
- •Subjects must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
排除标准
- •Female subjects who are pregnant, intend to become pregnant or are nursing
- •Patients previously treated with BRAF/MEK inhibitor or anti-PD-1/PD-L1 therapy in the metastatic setting
- •Uncontrolled intercurrent illness including, but not limited to, serious infection. Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
- •Patients with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 90 days prior to randomization
- •Patients with untreated or uncontrolled brain metastases. Patients with asymptomatic brain metastases which have been previously treated (with locoregional treatment such as radiation or surgery) and are clinically stable (i.e. not requiring corticosteroids) at the time of study start will be eligible
- •Previous malignancy is not an exclusion provided that the other malignancy is considered under control, patient is not on concomitant anti-cancer drug therapy, and target lesions from melanoma are clearly defined for response assessment
研究组 & 干预措施
Arm A: BRAF-MEK Inhibitor Therapy
Participants will receive 450 mg Encorafenib daily, along with 45 mg Binimetinib twice daily and 240 mg Nivolumab IV every 2 weeks.
干预措施: Encorafenib (Drug)
Arm A: BRAF-MEK Inhibitor Therapy
Participants will receive 450 mg Encorafenib daily, along with 45 mg Binimetinib twice daily and 240 mg Nivolumab IV every 2 weeks.
干预措施: Binimetinib (Drug)
Arm A: BRAF-MEK Inhibitor Therapy
Participants will receive 450 mg Encorafenib daily, along with 45 mg Binimetinib twice daily and 240 mg Nivolumab IV every 2 weeks.
干预措施: Nivolumab (Drug)
Arm B
Participants will receive 240 mg Nivolumab IV every 2 weeks
干预措施: Nivolumab (Drug)
结局指标
主要结局
8 Week Completion Rate
时间窗: At the end of the first 8 week treatment period
Number of participants who reach 8 weeks with the prescribed on/off schedule without progression of disease. Progression as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
次要结局
- Time to Treatment Failure(Up to 5 years)
- Objective Tumor Response Rate(Up to 5 years)