COMBI-APlus: Open-label, Phase IIIb Study of Dabrafenib in COMBInation With Trametinib in the Adjuvant Treatment of Stage III BRAF V600 Mutation-positive Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes of an Adapted Pyrexia AE-management Algorithm (Plus)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 552
- 试验地点
- 1
- 主要终点
- Composite Rate of Pyrexia Related Events
研究概览
简要总结
The main purpose of this study was to evaluate the impact on pyrexia-related outcomes of an adapted pyrexia adverse event (AE)-management algorithm, as well as safety, efficacy and health-related outcomes.
详细描述
This was an open-label Phase IIIb study of dabrafenib in combination with trametinib in the adjuvant treatment of melanoma after complete resection. Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk cutaneous melanoma were screened for eligibility.
This study consisted of two periods:
- Treatment Period - patients received up to 12 months of dabrafenib (150 mg twice daily) and trametinib (2 mg once daily). In the adapted pyrexia management algorithm, dabrafenib and trametinib were interrupted promptly at the onset of pyrexia (≥38°C) and were restarted upon the improvement of symptoms at the same dose if patients remained symptom free (temperature <38°C) for at least 24 hours. In addition, dabrafenib and trametinib could be interrupted in the presence of pyrexia syndrome (i.e. chills, rigours, night sweats, or influenza-like symptoms) without documented temperature ≥38°C for cases of suspected recurrent pyrexia, at the investigators' discretion.
- Follow-up Period - patients were followed for disease relapse through 24 months from first dose date. Moreover, patients were followed for overall survival through withdrawal, lost to follow-up, death, or the end of study, whichever occurs first. The follow-up period started once treatment was completed or treatment was prematurely discontinued.
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
- •Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)] no more than 12 weeks, from last surgery, before Day 1
- •Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma were eligible.
- •Subjects who had previously had Stage III melanoma at any time were not eligible.
- •Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).
- •V600E/K mutation positive using a validated local test
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
排除标准
- •Uveal or mucosal melanoma
- •Evidence of metastatic disease including unresectable in-transit metastasis
- •Received any prior adjuvant or neoadjuvant treatment, including but not limited to chemotherapy, checkpoint inhibitors, targeted therapy [e.g., BRAF and/or MEK inhibitors], biologic therapy, vaccine therapy, investigational treatment, or radiotherapy for melanoma
- •Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and had not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ
- •History or current evidence of cardiovascular risk
- •A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy
研究组 & 干预措施
Dabrafenib and trametinib combination therapy
Subjects received dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) orally for up to 12 months.
干预措施: Dabrafenib (Drug)
Dabrafenib and trametinib combination therapy
Subjects received dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) orally for up to 12 months.
干预措施: Trametinib (Drug)
结局指标
主要结局
Composite Rate of Pyrexia Related Events
时间窗: Baseline up to 12 months
The composite rate of pyrexia related events was calculated as the total number of participants experiencing at least one of the three components of the composite endpoint (i.e., grade 3/4 pyrexia, hospitalization due to pyrexia, or permanent treatment discontinuation due to pyrexia), divided by the total number of participants treated in the study and multiplied by 100. Pyrexia is defined as fever ≥ 38 °C. Pyrexia events were graded by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Life-threatening) and Grade 5 (Death)
次要结局
- Overall Survival (OS) Rate(At 12 and 24 months)
- Relapse Free Survival (RFS) Rate(At 12 and 24 months)
- Change From Baseline in Subject-reported Quality of Life (QoL) Assessed by Functional Assessment Cancer Therapy - Melanoma Subscale Score (FACT-M MS)(Baseline up to 24 months)
- Percentage of Participants Who Permanently Discontinued Treatment Due to Any Adverse Event (AE)(Baseline up to 12 months)
- Percentage of Participants Who Required Management of Pyrexia(Baseline up to 12 months)