Circulating Tumour DNA Guided Adaptive BRAF and MEK Inhibitor Therapy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 40
- 主要终点
- To measure tumour response to re-introduction of encorafenib plus binimetinib following the first "drug off " period.
研究概览
简要总结
The goal of this clinical trial is to investigate adaptive therapy in late-stage cutaneous melanoma. The main question it aims to answer are:
If the patient having breaks in their treatment allows the less resistant cells to continue to grow, this would result in a tumour with a lower proportion of resistant cells, making the tumour less resistant to the treatment, an increasing the time it takes for the disease to progress?
Participants will
- Receive their allocated treatment regimen until their cancer progresses, they or their doctor withdraw them from the study, or until the study ends, whichever happens first.
- Attend fortnightly visits to hospital.
- Complete EORTC QLQ-C30 and PRO-CTCAE questionnaires, prior to treatment, every 12 weeks and at the point of cancer progression, to assess quality of life.
Researchers will compare the adaptive therapy participant arm with a standard of care arm to answer the research question described above.
详细描述
Encorafenib and binimetinib given in combination ("the treatment") is a standard of care treatment in the UK for late stage cutaneous melanoma, a skin cancer that starts in the cells that produce skin pigmentation. 'Late stage' means it can't be surgically removed, or has spread. The treatment is taken daily. Resistance to the treatment can develop after about 12-15 months. During this period, the treatment will kill the less resistant cells, meaning the tumour has a greater proportion of cells that are resistant to the treatment.
This study aims to investigate if the patient having breaks in their treatment allows the less resistant cells to continue to grow, this would result in a tumour with a lower proportion of resistant cells, making the tumour as a whole less resistant to the treatment, and increasing the time it takes for the disease to progress. A blood test that measures the amount of tumour DNA circulating in the patient's blood (known as ctDNA) will be conducted every two weeks to check if the cancer cells are still present, and if they are becoming active. The result of this test will allow doctors to monitor the activity of the tumour and judge when to pause and resume treatment. This intermittent treatment is called 'adaptive therapy'. The investigators intend to recruit 40 participants with late stage cutaneous melanoma from NHS hospitals in the UK. Ten will receive the standard, daily treatment, and thirty will receive adaptive therapy. Patients will receive their allocated treatment regimen until their cancer progresses, they or their doctor withdraw them from the study, or until the study ends, whichever happens first. As well as the fortnightly visits to hospital, patients will required to complete EORTC QLQ-C30 and PRO-CTCAE questionnaires in order for their quality of life to be assessed. These will be completed before their treatment starts; every 12 weeks from when they start treatment; and again if their cancer progresses.
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
- Single (Participant)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
ARM A: Standard of care
Continuous dosing of encorafenib 450mg once daily plus binimetinib 45mg twice daily.
干预措施: Standard of Care (Drug)
ARM B: Adaptive therapy
4 weeks of encorafenib 450mg once daily plus binimetinib 45mg twice daily, followed by adaptive cycles based on ctDNA TAB level
干预措施: Adaptive Therapy (Drug)
结局指标
主要结局
To measure tumour response to re-introduction of encorafenib plus binimetinib following the first "drug off " period.
时间窗: 3 years (Longitudinally throughout the study)
Specific measure: Maximal reduction in percentage ctDNA mutant BRAF copies/ml of plasma from baseline 2 TAB level upon restart of E+B following first drug off period.
次要结局
- To measure the thresholds of percentage reduction in TAB level in ctDNA as a measure of response to stop drugs and the percentage increase in TAB as a decision to restart drugs.(3 years (Longitudinally throughout the study))
- To measure progression free survival (PFS) in Arm A vs. Arm B(3 years (Continuously throughout the study))
- To measure melanoma specific overall survival in Arm A vs. Arm B(3 years (Continuously throughout the study))
- To measure toxicity (all grade adverse events) in Arm A vs. Arm B(3 years (Continuously throughout the study))
- To measure maximal response (complete response (CR)/partial response (PR)/stable disease (SD)/progressive disease (PD)) to therapy in Arm A vs. Arm B(Randomisation until RECIST progression/clinical deterioration (estimated 12 months))
- To measure number of adaptive therapy cycles completed by participants on Arm B(3 years (Longitudinally throughout the study))
- To measure median duration of adaptive therapy cycles completed by participants on Arm B(3 years (Longitudinally throughout the study))
- To measure quality of life in Arm A vs. Arm B(3 years (Longitudinally throughout the study))
- To measure time to clinical deterioration in Arm A vs. Arm B.(3 years (Continuously throughout the study))
- To measure overall survival in Arm A vs. Arm B(3 years (Continuously throughout the study))
- To measure whether ctDNA result can be provided within 5 working days from sample receipt into NBC(3 years (Longitudinally throughout the study))