A Prospective Non Interventional Study on Targeted Therapy for Patients With Unresectable or Metastatic BRAFV600E Mutant Melanoma
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- Description of age
研究概览
简要总结
- Background The purpose of this study is to describe the profile of patients with BRAF-mutated melanoma treated with BRAF/MEK inhibitors combination and using the Tavie Skin application.
TavieSkin app, a digital solution developped by Pierre Fabre, is dedicated to all BRAF-mutant unresectable or metastatic melanoma patients who are treated with "any" targeted therapies. 2. Study objectives The primary objective of the survey is to describe the demographics and clinical characteristics of patients with unresectable or metastatic BRAF-mutated melanoma treated with targeted therapy (BRAFi/MEKi) and using the TavieSkin application
The secondary objectives include:
- To assess the use of TavieSkin app in patients with unresectable or metastatic BRAF-mutated melanoma treated with BRAFi/MEKi combination;
- To assess the treatment adherence of patients using TavieSkin app including treatment interruption or permanent discontinuation;
- To assess the health-related quality of life of patients using TavieSkin app (FACT-M);
- To assess work productivity and activity impairment over the treatment duration
- To assess the patient satisfaction toward the TavieSkin application;
- To assess the patient satisfaction toward the treatment.
- Research methods
3.1 Study design This prospective, longitudinal, survey will be conducted in Europe to characterize BRAF-mutant unresectable or metastatic melanoma patients using TavieSkin app designed for accompanying patients treated with targeted therapies.
To date, there are three combinations of BRAFi/MEKi available in routine practice for the treatment of BRAF-mutant unresectable or metastatic melanoma. The survey does not provide or recommend any treatment or procedure; all decisions regarding treatment are made at the sole discretion of the treating physicians in accordance with their usual practices. The patients initiating any BRAFi/MEKi combination will be invited to use the TavieSkin app by their healthcare provider (HCP) (i.e. oncologist, dermatologist, nurse…).
Once the patient has installed and started to use the application, an e-survey will be proposed to the patient via the app. A detailed information letter about the data collection, data privacy and analysis will be displayed to the patient via the app along with an e-consent for data collection. The patient will be able then to provide an e-signature, if he/she accepts to take part of this survey. The survey will collect anonymized data about health status, QoL data and satisfaction. These data will be collected by the patient only. The physician will not be involved in this e-survey (including e-consent), nor in data collection.
Only patients having given consent (e-consent) to data collection and analysis will be included. Data will be collected at baseline and at different subsequent timepoints during the BRAFi/MEKi treatment duration only. Only data reported by the patients in the application will be collected and analyzed.
The patient will discontinue the study in case of definitive withdrawal of BRAFi/MEKi treatment, or if he/she decides to withdraw the study and to stop data collection.
The target countries for patient enrollment will include Germany, Belgium, Portugal, France, Spain, Italy and Sweden with the additional possibility of including patients from other EU countries.
At least, 400 adult patients (≥18 years) will be enrolled.
3.2 Population (see section: Eligibility)
3.3 Study outcomes (see section: Outcome measures)
3.4 Statistical considerations Statistical analyses will be fully described in a written statistical analysis plan (SAP). The study endpoints will be analysed overall and by country. Analyses will be descriptive in nature, as no hypothesis will be tested.
The treatment patterns of patients, baseline demographics and clinical characteristics, and reasons for treatment discontinuation will be described using summary statistics. Categorical variables will be summarized by frequencies and percentages. Continuous variables will be summarized by descriptive statistics (mean, and standard deviation, median, 25th and 75th percentiles, minimum and maximum). The number of missing observations for each variable will also be reported.
Change in health-related quality-of-life scores (i.e. (FACT-M) will be summarised at baseline and at each timepoints. The change from baseline will be assessed using a mixed model for repeated measures (MMRM).
Time to event data (i.e. time to treatment discontinuation, time QoL deterioration) will be evaluated using Kaplan-Meier survival curves. Median survival estimates will be reported along with the 25th and 75th percentiles and corresponding 95% confidence intervals (CIs). Cox regression analysis may be performed to adjust for predefined (baseline) covariates.
If the sample size is adequate, subgroup analyses using variables at baseline might be conducted.
详细描述
- BACKGROUND AND RATIONALE
1.1 BACKGROUND
Melanoma: overview of disease and management options Melanoma is one of the most aggressive cancers and is responsible for the majority of skin cancer deaths (Miller, 2006; Potrony, 2015; Ryu, 2017), with the presence of metastases prognostic for poor survival. In Europe, BRAF V600-positive mutations are present in 40%-60% of cases of metastatic melanoma (Moreau, 2012; Rutkowsi, 2014; Arance Fernández, 2015; Picard, 2014; Colombino, 2013), with the V600E variant being the most common (in up to 90% of BRAF V600 mutation-positive melanomas). BRAF mutations are associated with a younger age at onset, higher number of melanocytic nevi, melanoma location in the trunk region and intermittently UV-exposed skin (Rutkowski, 2014; Colombino, 2013; Carlino, 2014; Ekedahl, 2013; Long, 2011).
Although mortality from melanoma has decreased over last decades, survival rate varies considerably based on the disease stage at diagnosis. The 5-year survival rate is above 90% for patients diagnosed localised tumours, 24 to 88% for stage III, and 10-25% for stage IV (Svedman, 2016; Schoffer, 2016; Jochems, 1990; Gershenwald, 2017). This together with a growing incidence of the disease and a substantial decline in patient health-related quality of life (HRQoL) (Hinz, 2014) as disease advances, make the management of metastatic melanoma a critical public health issue.
In Europe, the European Society for Medical Oncology (ESMO) guidelines are the most important international treatment guidelines that guide the clinical management of melanoma patients. They also form the basis for the development of local/ country-specific guidelines and treatment protocols. These guidelines have been updated recently (Michielin, 2019). New therapeutic strategies, such as immunotherapy (cytotoxic T-lymphocyte antigen 4 [CTLA-4] inhibitors and programmed cell death 1 [PD-1] inhibitors) and selective BRAF inhibitors are deemed the backbone of systemic therapy in melanoma. For BRAFV600 mutation-positive tumours, depending on patient characteristics, immunotherapies or combination of BRAF/MEK inhibitors are recommended. In second-line, selection depends on the strategy used for the first-line. BRAFis/MEKis is the main option if not used in the first-line setting. There are no specific recommendations on the use of one BRAF or MEK inhibitor over another.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Only patients starting to use the TavieSkin app will be eligible for enrollment in the survey.
- •The patient should meet all the following inclusion criteria to be eligible for participating:
- •Male or female aged ≥18 years at diagnosis of unresectable or metastatic melanoma;
- •Diagnosis of histologically or cytologically confirmed BRAF-mutant melanoma that is metastatic or unresectable, documented as per routine practice
- •Patient having an ongoing prescription of one of the three commercially available BRAFi/MEKi combination therapy, at any line of treatment
- •Patient using the TavieSkin app and having signed an informed consent (e-consent via the app) for data collection , according to local regulations
排除标准
- •Patients will be excluded from the survey if they fulfil any of the following criteria:
- •Patients with other BRAFi/MEKi combination than those available on the market
- •Patient receiving a BRAFi/MEKi combination in the adjuvant setting
- •Patients under guardianship because of mental illness or any other reason
- •Patients treated with a treatment that is not licensed for local use (including approved BRAFi/MEKi combination associated with another product)
结局指标
主要结局
Description of age
时间窗: Baseline
Age will be assessed in years (date of the initiation of targeted therapy - date of birth)
Description of Sex
时间窗: Baseline
Sex will be described in percentage of Male and Female among the participants
Description of BMI
时间窗: Baseline
Weight (in kg) and height (in m) will be combined to report BMI in kg/m2
Description of sociodemographic status: country
时间窗: Baseline
The country will be described in number of participants included in each country (France, Portugal, Spain, Belgium, Germany, Italy)
Description of sociodemographic status: education level
时间窗: Baseline
The education level will be described by the following distribution of participants: with no degree/Primary education, High school level or equivalent and with college degree (i.e. Bachelor, Master or Doctorate)
Description of sociodemographic status: employment status
时间窗: Baseline
The employment status will be described by the following distribution of participants: employed, unemployed, retired and student
Description of sociodemographic status: living place
时间窗: Baseline
The living place will be described by the following distribution of participants: living in urban/suburban and in rural
Description of sociodemographic status: family situation
时间窗: Baseline
The family situation will be described by the following distribution of participants: living alone, cohabiting or living with family members and other
Description of clinical characteristics of patients: time since initial diagnostic of melanoma
时间窗: Baseline
The time since initial diagnostic of melanoma will be assessed in number of years (date of the initiation of targeted therapy - date of initial diagnostic of melanoma)
Description of clinical characteristics of patients: time since metastatic diagnosis
时间窗: Baseline
The time since metastatic diagnosis will be assessed in number of years (date of the initiation of targeted therapy - date of metastatic diagnosis)
Description of clinical characteristics of patients: initial/primary site of tumor
时间窗: Baseline
The Initial/primary site of tumor will be described by the following distribution of participants: with localization in the upper extremities, head and neck, trunk, lower extremities, mucosal or uvea, unknown localization
Description of clinical characteristics of patients: comorbidities
时间窗: Baseline
The comorbidities will be described by the following distribution of participants: with diabetes, hypertension, renal failure, cardiovascular disease, other cancer, autoimmune disease, …
Description of clinical characteristics of patients: prior therapies for melanoma
时间窗: Baseline
The prior therapies for melanoma will be described by the following distribution of participants: treated with surgery, radiotherapy, chemotherapy, immunotherapy, targeted therapy, other
次要结局
- Assessment of the activity and the physical function(Baseline, then every month during targeted therapy until targeted therapy discontinuation or study completion, an average of 1 year, whichever comes first)
- Assessment of the use of TavieSkin application: duration of usage per day(Every day during targeted therapy until targeted therapy discontinuation or study completion, an average of 1 year, whichever comes first)
- Assessment of health-related quality of life.(Baseline, then every 6 weeks during targeted therapy until targeted therapy discontinuation or study completion, an average of 1 year, whichever comes first)
- Assessment of the patient satisfaction toward the TavieSkin application(Every 2 months during targeted therapy until targeted therapy discontinuation or study completion, an average of 1 year, whichever comes first)
- Assessment of the use of TavieSkin application: rate of completed data and completed questionnaires(Every day during targeted therapy until targeted therapy discontinuation or study completion, an average of 1 year, whichever comes first)
- Assessment of the adherence to treatment(Every day during targeted therapy until targeted therapy discontinuation or study completion, an average of 1 year, whichever comes first)
- Assessment of Work productivity and activity impairment(Baseline, then every 2 months during targeted therapy until targeted therapy discontinuation or study completion, an average of 1 year, whichever comes first)
- Assessment of the use of TavieSkin application:number of subscribers who frequently use the application(Every day during targeted therapy until targeted therapy discontinuation or study completion, an average of 1 year, whichever comes first)
- Assessment of the patient satisfaction toward the treatment(Every 2 months during targeted therapy until targeted therapy discontinuation or study completion, an average of 1 year, whichever comes first)