Evaluation of Groin Lymphadenectomy Extent For Metastatic Melanoma (EAGLE FM)
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|ClinicalTrials.gov Identifier: NCT02166788|
Recruitment Status : Recruiting
First Posted : June 18, 2014
Last Update Posted : September 11, 2019
BACKGROUND: Spread of metastatic melanoma to the groin lymph nodes (LN) is a common event affecting about 350 people a year in Australia. Globally it has been shown that patients with involved groin LN, without proven pelvic LN disease on imaging receive 1 of 3 management strategies in equal proportions - inguinal lymphadenectomy (IL); ilio-inguinal lymphadenectomy (I-IL); or variable use of either depending on circumstances. Different experts have strong and polarised opinions favouring either IL or more extensive I-IL with existing cases series reporting conflicting data on best cancer outcomes. No high level evidence proves which operation is best. HYPOTHESIS: There will be no significant difference in DFS between patients having IL or I-IL, conditional on PET/CT scan showing no evidence of pelvic disease at the time of diagnosis of groin LN metastatic melanoma. AIMS: To provide a rational evidence base for management for melanoma to the groin LNs by randomly assessing the effect of each operation on DFS, distant DFS, overall survival (OS), morbidity - including early complications and longer-term rates of lymphedema as well as comprehensively assessed QOL. Also to clarify the reliability of PET/CT scans for staging pelvic LNs and evaluate any health economic benefits of I-IL over IL. TARGET POPULATION: To recruit 634 patients in 5 years. DESIGN: An Australian led, international, multi-centre, non-inferiority, phase III, prospective, randomised clinical trial comparing IL or I-IL for patients with metastatic melanoma to groin LNs and no evidence of pelvic disease on PET/CT. ENDPOINTS: DFS, Distant DFS, OS and QOL at 5 years. Accuracy of PET/CT for pelvic LN metastases.
OUTCOMES: International standardization of care, improved cancer outcomes, improved QOL for patients with groin metastatic melanoma. Proof of principle about extent of surgery when PET/CT is clear in adjacent LN areas, leading to clinical trials investigating management of other lymph node fields.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Melanoma to the Groin Lymph Nodes||Procedure: Inguinal Lymphadenectomy Procedure: Ilio-inguinal Lymphadenectomy||Phase 3|
Background and Rationale
Spread of metastatic melanoma to the groin lymph nodes (LN) is a common event for patients with melanoma. In melanoma treatment centres around the world, patients without demonstrated pelvic LN disease receive 1 of 3 strategies of management in relatively equal proportions (Pasquali, Spillane et al. 2012):
i. Inguinal Lymphadenectomy (IL) ii. Ilio-inguinal Lymphadenectomy (I-IL) iii. Variable use of either IL or I-IL surgery.
Some larger melanoma centres have an institutional policy that all patients have either IL or I-IL for metastatic inguinal node involvement. Nearly all centres would agree that patients with pelvic LN involvement without distant metastatic disease should have I-IL.
Study Objectives This study aims to provide a more rational evidence base for appropriate management for metastatic melanoma in the groin LNs, through assessing the effect of the addition of ipsilateral pelvic lymphadenectomy on patient disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), morbidity, and quality of life. In addition, the study will clarify the reliability of PET (Positron Emission Tomography) / CT (Computed Tomography) scans for staging pelvic LNs, clarify morbidity differences between the operations in a balanced cohort, evaluate any health economic benefits of I-IL over IL and provide a tissue and serum resource to be used to identify biological markers of recurrence and progression after inguinal metastases.
Study Hypothesis There will be no significant difference in DFS between patients having IL or I-IL, conditional on PET/CT scan showing no evidence of pelvic disease at the time of diagnosis of groin LN metastatic melanoma.
Study Population The aim is to recruit 634 patients in 5 years who are 15 years or older with cytologically or histologically confirmed metastatic melanoma in inguinal LNs (H&E & IHC); specifically with no evidence of pelvic node involvement or distant spread of melanoma clinically or on PET/CT staging scans. To be eligible patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 at randomisation.
Study Treatments Eligible patients will be randomised 1:1 to undergo an IL or I-IL.
Study Design This is an international, multi-centre, phase III, non-inferiority, prospective, randomised clinical trial.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||634 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Inguinal or Ilio-inguinal Lymphadenectomy for Patients With Metastatic Melanoma to Groin Lymph Nodes and no Evidence of Pelvic Disease on PET/CT Scan - A Randomised Phase III Trial (EAGLE FM)|
|Study Start Date :||January 2015|
|Estimated Primary Completion Date :||August 2025|
|Estimated Study Completion Date :||August 2030|
Arm 1: Inguinal Lymphadenectomy
Inguinal Lymphadenectomy (IL) is removal of the easily accessible superficial groin lymph nodes (LNs) and has a median LN retrieval of 11 lymph nodes
Procedure: Inguinal Lymphadenectomy
Arm 2: Ilio-inguinal Lymphadenectomy
Ilio-inguinal Lymphadenectomy (I-IL) is the removal of the same superficial groin lymp nodes (LN) removed during an IL but also combined with the more surgically complex removal of the ipsilateral pelvic LN. About twice as many LN are removed with I-IL compared to IL.
Procedure: Ilio-inguinal Lymphadenectomy
- The primary endpoint of the study will be Disease Free Survival following lymphadenectomy, assessed after 60 months of follow-up. [ Time Frame: 60 Months ]The difference between IL and I-IL surgery in DFS 5 years after randomisation
- Overall Survival [ Time Frame: 0 - 120 months ]time from randomisation to death from any cause
- Distant Disease Free Survival [ Time Frame: 0 - 120 Months ]time to new distant melanoma recurrence
- Regional Recurrence Free Survival [ Time Frame: 0 - 120 Months ]time to new regional lymph node recurrence
- Morbidity differences [ Time Frame: Up to 120 days from lymphadenectomy, and from 0 - 120 months ]This includes lymphoedema, wound complications (wound infections, dehiscence/necrosis, and seroma) chronic pain, and restriction in mobility
- Quality Of Life [ Time Frame: 0 - 120 Months ]Quality Of Life questionnaires completed by patients
- Sensitivity / specificity and positive predictive value and negative predictive value of PET/CT for pelvic disease at diagnosis of groin LN involvement by melanoma. [ Time Frame: 0 - 120 Months ]The diagnostic accuracy of PET/CT and CT for detecting pelvic lymph nodes positive for metastatic melanoma as confirmed by histopathology will be assessed in the sub-group of patients screened and shown to have a positive pelvic LN on PET/CT and those patients who had negative pelvic LN on PET/CT and randomised for I-IL treatment.
- Resource use and utility based Quality Of Life [ Time Frame: 0 - 60 Months ]Resource use will be identified from the trial case report forms, and valued according the relevant Australian Refined Diagnosis Related Groups and Medicare Benefits Schedule item numbers.The cost-effectiveness and cost-utility analyses will calculate total costs and mean per patient costs per surgical group allocation, as well as total and mean benefits per group allocation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02166788
|Contact: Narelle Williams||+ 61 2 9911 email@example.com|
|Principal Investigator:||Andrew Spillane||The University of Sydney, Northern Clinical School|