A Randomized Phase III Study of Management of Treatment Naive Primary Melanoma in Elderly Patients
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 428
- 试验地点
- 182
- 主要终点
- Recurrence free survival (RFS) rate
研究概览
简要总结
This phase III trial compares the effect of wide local excision (WLE) alone to usual care with WLE plus sentinel lymph node (SLN) biopsy for the treatment of older adults with early-stage melanoma. A WLE is a surgical procedure performed to cut out an abnormal lesion and some surrounding normal tissue. This is sometimes followed by a SLN biopsy, in which lymph nodes that tumor cells could spread to are removed as well. Using WLE alone may be just as effective as usual care in treating older adults with early-stage melanoma.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate and compare 2-year recurrence-free survival (RFS) rates in both study arms.
II. To evaluate patient-reported outcomes (PRO) at 2 years (as measured by the change in Functional Assessment of Cancer Therapy-Melanoma [FACT-M] total score) in both study arms.
SECONDARY OBJECTIVES:
I. To evaluate and compare RFS, overall survival (OS), melanoma-specific survival (MSS), safety and PRO (at various endpoints).
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 (Participant)
入排标准
- 年龄范围
- 75 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must be ≥ 75 years of age.
- •Patient must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.
- •Patient must have newly diagnosed primary cutaneous melanoma with wide local excision (WLE) and sentinel lymph node (SLN) biopsy indicated per the treating physician, pending definitive surgical management.
- •NOTE: For WLE and SLN to be indicated, the patient must have either:
- •Pathologic features that include ≧ Breslow 0.8 mm OR Breslow < 0.8 mm determined at initial biopsy, with a positive margin, ulceration, lymphovascular invasion, perineural invasion or > 1 mitosis/mm^
- •Risk of SLN metastasis of at least 5%, as calculated using the Melanoma Institute of Australia (MIA) Sentinel Node Metastasis Prediction Tool.
- •Patient must be eligible for WLE and SLN biopsy. Patients for whom SLN biopsy would be contraindicated, difficult to perform (i.e., after prior surgery in the draining basin) or impossible (i.e., after prior lymphadenectomy for another cause) are not eligible.
- •Patient must be eligible for surgery and not have uncontrolled medical condition that in the opinion of the medical or surgical oncologist precludes surgical management.
- •Patient must not have an active infection that precludes enrollment to this study in opinion of treating investigator.
- •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial.
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- •Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better.
- •Patient must be English speaking to be eligible for this study in order to complete the patient-reported outcomes (PROs).
- •NOTE: Sites cannot translate the associated quality of life (QOL) forms.
排除标准
- •Patient must not have an active infection that precludes enrollment to this study in opinion of treating investigator.
- •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial.
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- •Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
研究组 & 干预措施
Arm A (WLE, SLN biopsy)
Patients undergo WLE plus SLN biopsy and may undergo surveillance of nodal basin as usual care on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Adjuvant Therapy (Procedure)
Arm A (WLE, SLN biopsy)
Patients undergo WLE plus SLN biopsy and may undergo surveillance of nodal basin as usual care on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Comprehensive Geriatric Assessment (Other)
Arm A (WLE, SLN biopsy)
Patients undergo WLE plus SLN biopsy and may undergo surveillance of nodal basin as usual care on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Computed Tomography (Procedure)
Arm A (WLE, SLN biopsy)
Patients undergo WLE plus SLN biopsy and may undergo surveillance of nodal basin as usual care on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Positron Emission Tomography (Procedure)
Arm A (WLE, SLN biopsy)
Patients undergo WLE plus SLN biopsy and may undergo surveillance of nodal basin as usual care on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Questionnaire Administration (Other)
Arm A (WLE, SLN biopsy)
Patients undergo WLE plus SLN biopsy and may undergo surveillance of nodal basin as usual care on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Sentinel Lymph Node Biopsy (Procedure)
Arm A (WLE, SLN biopsy)
Patients undergo WLE plus SLN biopsy and may undergo surveillance of nodal basin as usual care on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Surveillance (Behavioral)
Arm A (WLE, SLN biopsy)
Patients undergo WLE plus SLN biopsy and may undergo surveillance of nodal basin as usual care on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Ultrasound Imaging (Procedure)
Arm A (WLE, SLN biopsy)
Patients undergo WLE plus SLN biopsy and may undergo surveillance of nodal basin as usual care on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Wide Local Excision (Procedure)
Arm B (WLE)
Patients undergo WLE and surveillance of nodal basin on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Adjuvant Therapy (Procedure)
Arm B (WLE)
Patients undergo WLE and surveillance of nodal basin on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Comprehensive Geriatric Assessment (Other)
Arm B (WLE)
Patients undergo WLE and surveillance of nodal basin on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Computed Tomography (Procedure)
Arm B (WLE)
Patients undergo WLE and surveillance of nodal basin on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Positron Emission Tomography (Procedure)
Arm B (WLE)
Patients undergo WLE and surveillance of nodal basin on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Questionnaire Administration (Other)
Arm B (WLE)
Patients undergo WLE and surveillance of nodal basin on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Surveillance (Behavioral)
Arm B (WLE)
Patients undergo WLE and surveillance of nodal basin on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Ultrasound Imaging (Procedure)
Arm B (WLE)
Patients undergo WLE and surveillance of nodal basin on study. Patients may receive adjuvant therapy as clinically indicated. Additionally, patients may undergo CT, PET/CT or ultrasound throughout the study.
干预措施: Wide Local Excision (Procedure)
结局指标
主要结局
Recurrence free survival (RFS) rate
时间窗: From randomization to recurrence of disease or death from any cause, assessed at 2 years
Will evaluate RFS rate. Will compare the co-primary endpoints in a hierarchical manner starting with RFS rate. The 2-year RFS rate will be estimated from the Kaplan-Meier curve and compared between treatment arms via two sample binomial test, and the 95% confidence interval (CI) will be provided. Will be measured on the intention-to-treat patient cohort. Patients that have not had an event reported at analysis will be censored at their date of last follow-up. Patients who drop out or are lost to follow up before 2 years will be censored.
Patient reported outcome (PRO)
时间窗: Baseline to 2 years
Will compare the co-primary endpoints in a hierarchical manner starting with RFS rate. If RFS rate in non-inferior (wide local incision \[WLE\] is non-inferior to WLE plus sentinel lymph node biopsy) will proceed to evaluate PRO as a co-primary endpoint. Will measure patients quality of life by Functional Assessment of Cancer Therapy-Melanoma (FACT-M) score. The FACT-M score change will be calculated by FACT-M score at 2 years minus the FACT-M score at baseline. Descriptive analyses will be conducted for baseline scores, 2-year scores and the change. The change scores will be compared between the two study arms with two sample t test. 95% CI will be provided. If RFS rate is inferior will proceed to evaluate PRO as an exploratory endpoint.
Patient-Reported Outcome (PRO) Component
时间窗: (FACT-M) baseline 4 months 8 months 12 months 16 months 20 months 24 months
The patient reported outcomes (PRO) in this study include a Geriatric Assessment (GA) and the FACT-M Quality of Life (QOL). The National Comprehensive Cancer Network (NCCN) guidelines advocate geriatric assessment (GA) for older patients with cancer to identify health status issues that increase the risk of adverse outcomes. A GA evaluates comorbidity, functional status, physical performance, cognitive ability, psychological status, medications and social support with standardized tools that predict morbidity and mortality in community-dwelling vulnerable older adults. Benefits of GA in community-dwelling vulnerable older adults include prevention of geriatric syndromes, recognition of cognitive deficits, addressing geriatric abnormalities detected by the assessment to prevent hospitalizations and nursing home admissions, and overall improvement of quality of life.
次要结局
- RFS(From randomization to recurrence of disease or death from any cause, assessed up to 2 years)
- Overall Survival (OS)(From randomization to death from any cause, assessed up to 2 years)
- Melanoma-specific survival (MSS)(From randomization to death due to melanoma, assessed up to 2 years)
- Incidence of adverse events (AEs)(Baseline to after surgery)
- PRO(Up to 5 years)
- Geriatric factors(Baseline to 5 years)
- Geriatric Assessment (GA)(Geriatric Assessment (at years 1 and 2 during the surveillance stage and at the time of disease recurrence).)