Comparing the Effectiveness of Less Invasive Procedures With the Current Standard of Care for the Treatment of Older Adults With Early-Stage Melanoma

Phase 3RecruitingNCT07068074

ECOG-ACRIN Cancer Research Group428 enrolled

Overview

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.

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). II. To evaluate the correlation between practical geriatric assessment (PGA) findings at baseline by domain and study outcomes including RFS, OS, MSS. III. To evaluate the correlation between changes in PGA scores over the study period and study outcomes including RFS, OS, MSS. IV. To use the baseline and follow up geriatric assessment (GA) data to develop an assessment tool to allow for future risk assessment for older adults with early-stage melanoma to guide the decision regarding surgical approach. V. To validate the practical geriatric assessment instrument with data obtained from this study. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: 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 computed tomography (CT), positron emission tomography (PET)/CT or ultrasound throughout the study. ARM B: 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. After completion of study treatment, patients are followed up every 4 months for 2 years post-randomization and then every 6 months until 5 years post-randomization.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Interventions

Adjuvant TherapyPROCEDURE

Receive adjuvant therapy

Comprehensive Geriatric AssessmentOTHER

Ancillary studies

Computed TomographyPROCEDURE

Undergo CT

Positron Emission TomographyPROCEDURE

Undergo PET/CT

Questionnaire AdministrationOTHER

Ancillary studies

Sentinel Lymph Node BiopsyPROCEDURE

Undergo SLN biopsy

SurveillanceBEHAVIORAL

Undergo surveillance of nodal basin

Ultrasound ImagingPROCEDURE

Undergo ultrasound

Wide Local ExcisionPROCEDURE

Undergo WLE

Eligibility

Sex: ALLMin age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patient must be ≥ 75 years of age. * Patient must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * 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\^2. OR * 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.

Locations (181)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

RECRUITING

Gulf Health Hospitals Inc/Infirmary Cancer Care - Malbis

Daphne, Alabama, United States

RECRUITING

Thomas Hospital

Fairhope, Alabama, United States

RECRUITING

Mobile Infirmary Medical Center

Mobile, Alabama, United States

Outcomes

Primary Outcomes

Recurrence free survival (RFS) rate

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.

Time frame: From randomization to recurrence of disease or death from any cause, assessed at 2 years

Patient reported outcome (PRO)

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.

Time frame: Baseline to 2 years

Secondary Outcomes

RFS

Will evaluate RFS. Will be measured on the intention-to-treat patient cohort. Survival analyses will be performed using the Kaplan-Meier curve and compared between the two treatment arms by stratified log-rank test. Estimates at 2 years will be summarized along with median time for those events that reach a median survival at or before 2 years.

Time frame: From randomization to recurrence of disease or death from any cause, assessed up to 2 years

Overall Survival (OS)

Will evaluate OS. Will be measured on the intention-to-treat patient cohort. Survival analyses will be performed using the Kaplan-Meier curve and compared between the two treatment arms by stratified log-rank test. Estimates at 2 years will be summarized along with median time for those events that reach a median survival at or before 2 years.

Time frame: From randomization to death from any cause, assessed up to 2 years

Melanoma-specific survival (MSS)

Will evaluate MSS. Will be measured on the intention-to-treat patient cohort. Survival analyses will be performed using the Kaplan-Meier curve and compared between the two treatment arms by stratified log-rank test. Estimates at 2 years will be summarized along with median time for those events that reach a median survival at or before 2 years. Patients who have not died will be censored at the date last known to be alive.

Time frame: From randomization to death due to melanoma, assessed up to 2 years

Incidence of adverse events (AEs)

Will evaluate AEs. All subjects will be included in the safety analysis, with toxicities graded according to National Cancer Institute Common Terminology Criteria for Adverse Events. Incidence tables will be generated to summarize incidence of patients reporting at least one episode of each specific AE, incidence of AEs causing withdrawals and incidence of serious AEs. Listing of AEs by patients will include the time to onset, the duration of each event, the severity of each event, and the relationship of the event to study therapy, whether it was a serious event, and whether it caused withdrawal.

Time frame: Baseline to after surgery

PRO

Will evaluate PRO. Quality of life questionnaires will be scored and summarized at each timepoint within and after 2 years. Parametric assumptions will be assessed using Shapiro-Wilk statistics and qqplots and non-parametric alternatives will be considered when necessary. Scores will be analyzed using an appropriate longitudinal modeling approach (e.g., mixed-effects linear modeling assuming normality of scores) to compare patterns over time between treatment groups.

Time frame: Up to 5 years

Geriatric factors

Will analyze geriatric factors evaluated by the baseline practical geriatric assessment domains, to better understand factors affecting older adults diagnosed with localized melanoma. Will investigate the associations of survival outcomes and practical geriatric assessment scores by domains. Will use Cronbach's alpha test to test for an internal consistency for each domain. Will also use the intra-class correlation test to assess the level of agreement of each domain score at different timepoints. Will use Cohen's kappa test to test the agreement over different timepoints for specific items of interest.

Time frame: Baseline to 5 years

Comparing the Effectiveness of Less Invasive Procedures With the Current Standard of Care for the Treatment of Older Adults With Early-Stage Melanoma

Overview

Conditions

Interventions

Eligibility

Locations (181)

Outcomes

Primary Outcomes

Secondary Outcomes