INTERIM: a Randomised Phase II Feasibility Study of INTERmittent Versus Continuous Dosing or Oral Targeted Combination Therapy in Patients With BRAFV600 Mutant Stage 3 Unresectable or Metastatic Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 79
- 试验地点
- 1
- 主要终点
- Recruitment Rate
研究概览
简要总结
This feasibility study aims to determine if intermittent dosing is deliverable, based on patient and professional willingness to take part in a randomised trial evaluating less rather than the standard durations of treatment. The trial will evaluate treatment compliance, Progression Free Survival and Quality of Life, to inform whether a subsequent definitive trial is justified and how it should be designed.
详细描述
Metastatic melanoma has a very poor prognosis: median overall survival is 8 months untreated and around 2 years even with optimal systemic therapies. A gene called BRAF is abnormal in about half of melanomas and biological agents targeting the BRAF pathway have been shown to extend life. They are now routinely available in NHS clinical practice.
Giving BRAF and MEK inhibitor drugs together offers the best anti-cancer treatment for these patients. However, treatment is limited by side-effects (often affecting the skin) and secondary resistance (which means the cancer regrows usually after about a year).
Laboratory experiments and case reports suggest intermittent dosing of these chronic orally administered drugs makes BRAF pathway inhibitors work for longer, extending life and reducing side effects. The INTERIM trial aims to test whether less treatment than usual is acceptable to patients and doctors and, potentially, more beneficial. The INTERIM trial also aims to develop better tools to monitor skin side-effects.
The target population will be male and female participants aged 18 and over with BRAFV600 mutant stage 3 unresectable or metastatic melanoma.Patients will be provided with information regarding the trial both through conversation with investigators and research nurses and in writing via a patient information sheet. Patients will be given time to ask questions and discuss with family/support structures before deciding to participate. If the patient agrees to take part, they will be asked to provide written consent.
Visit schedule for consenting patients:
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
- •Signed informed consent
- •Age ≥18 years old
- •Histologically or cytologically confirmed BRAFV600 mutant stage 3 unresectable or metastatic melanoma
- •Measurable disease by RECIST
- •ECOG performance status 0-2
- •Minimum life expectancy 12 weeks
- •Adequate bone marrow, renal and liver function
- •Received no prior BRAF or MEK inhibitor therapy for metastatic disease
- •Willing and able to comply with the scheduled visits, treatment plans, laboratory tests, completion of QoL questionnaires and other study procedures
- •Archival tumour tissue sample available
- •Women of child-bearing potential and all sexually active male patients must agree to use effective contraception methods throughout treatment
排除标准
- •Concomitant immunotherapy being administered to treat advanced melanoma
- •Other invasive malignancies diagnosed within the last year which are not in complete remission, or for which additional therapy is required
- •Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk or interfere with the trial
- •Women who are pregnant, plan to become pregnant or are lactating during the trial period
- •Other investigational anti-cancer drugs
- •Use of strong inducers and inhibitors of CYP3A or CYP2C8
研究组 & 干预措施
Continuous (Standard)
Dabrafenib 150mg twice daily 12 hours apart, on days 1-28 of a 28 day cycle plus Trametinib 2mg once daily, on days 1-28 of a 28 day cycle
干预措施: Dabrafenib (Drug)
Continuous (Standard)
Dabrafenib 150mg twice daily 12 hours apart, on days 1-28 of a 28 day cycle plus Trametinib 2mg once daily, on days 1-28 of a 28 day cycle
干预措施: Trametinib (Drug)
Intermittent (experimental)
Dabrafenib 150mg twice daily 12 hours apart, on days 1-21 of a 28 day cycle plus Trametinib 2mg once daily, on days 1-14 of a 28 day cycle
干预措施: Dabrafenib (Drug)
Intermittent (experimental)
Dabrafenib 150mg twice daily 12 hours apart, on days 1-21 of a 28 day cycle plus Trametinib 2mg once daily, on days 1-14 of a 28 day cycle
干预措施: Trametinib (Drug)
结局指标
主要结局
Recruitment Rate
时间窗: To be assessed once the trial has been recruiting for 15 months, or when 15 sites have been open for 6 months whichever is sooner
Average number of patients recruited per site per two months.
Treatment compliance
时间窗: 6 months from randomisation
percentage of patients completing the allocated treatment
Overall Quality of Life
时间窗: 6 months from randomisation
global health status score derived from (EORTC) QLQ-C30 questionnaire
Progression Free survival
时间窗: calculated as the duration from the date of randomisation to the date of first progression or death from any cause, whichever occurs first, assessed up to 5 years
Assessed according to standard Response Criteria in Solid Tumours (RECIST v1.1)
次要结局
- Patient Reported Outcomes focusing on skin toxicity evaluation(Through study completion, an average of 1 year)
- Objective response rate(Through study completion, an average of 1 year)
- Health Economic Evaluation(Through study completion, an average of 1 year)
- Incidence of treatment emergent adverse events (safety and tolerability)(Through study completion, an average of 1 year)
- Overall survival(Assessed up to 5 years)
- Patient Experience(Surveys at screening and after 9 months. Interviews by invitation at a later date)
- Time to treatment failure(Through study completion, an average of 1 year)
- Impact on Quality of Life(At 6 months from baseline)
研究者
CCTU- Cancer Theme
Consultant and Associate Lecturer in Medical Oncology
Cambridge University Hospitals NHS Foundation Trust