Clinical trial NCT03683550: Comparing SLNE With or Without Preoperative Hybrid SPECT/CT in Melanoma
Official title: Randomized Trial Comparing Sentinel Lymph Node Excision (SLNE) With or Without Preoperative Hybrid Single-photon Emission Computed Tomography/Computed Tomography (SPECT/CT) in Melanoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Melanoma
Keywords: SLNE
SPECT/CT
Lead sponsor: University Hospital, Essen
Sponsor class: OTHER
First posted: 2018-09-25
Enrollment: 836
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Melanoma has become a growing interdisciplinary problem in public health worldwide. It characteristically disseminates in an orderly progression through lymphatic channels to the regional lymph node and then to more distant sites.

Sentinel lymph node excision (SLNE) is probably the most important diagnostic and potentially therapeutic procedure for melanoma patients.

This is a randomized, open-label, multi-center, superiority, 2-parallel arms trial comparing sentinel lymph node excision with or without preoperative hybrid single photon emission computed tomography/computed tomography in patients with malignant melanoma.

Detailed description: The presence of regional lymph node involvement is the single most important prognostic factor, lowering the 5-year survival rate to approximately 50%.

Recommendations for the use of SLNE for primary melanoma are included in the current American Joint Committee on Cancer guidelines. Critics argue that the routinely performed SLNE is a cost intensive surgical intervention with potential morbidity that does not offer patients any advantage in overall survival. The current gold standard for detection and targeted extirpation of the sentinel lymph node (SLN) is preoperative lymphoscintigraphy as an imaging technique to identify the lymph drainage basin, determine the number of sentinel nodes, differentiate sentinel nodes from subsequent nodes, locate the sentinel node in an unexpected location, and mark the sentinel node over the skin for biopsy. Single-photon emission computed tomography/computed tomography (SPECT/CT) provides complementary functional and anatomical information and has been shown to be superior to planar imaging in a number of indications. It can provide valuable information before sentinel lymph node biopsy and advocate its use in a range of tumors such as truncal and head and neck melanomas.

The objective of the planned multi-center randomized prospective trial is to compare distant metastasis-free survival (DMFS) in patients with cutaneous melanoma between sentinel lymph node excision with versus without preoperative SPECT/CT imaging and metastatic node detection.

Eligibility criteria: Inclusion Criteria:

* Patients with malignant melanoma in AJCC stages Ib / II
* Tumor depth of ≥1.0 mm
* Age ≥18 years to ≤75 years
* Have a primary melanoma that is cutaneous (including head, neck, trunk, extremity, scalp, palm, sole, subungual skin tissues
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Life expectancy of at least 5 years from the time of diagnosis, not considering the melanoma in question, as determined by the principal investigator (PI)
* Willing to return to the trial center for follow-up examinations and procedures as outlined in the protocol
* Randomization must be completed no more than 120 days following the diagnostic biopsy of the primary melanoma
* Negative pregnancy test for female and effective contraception for both male and female subjects if the risk of conception exists
* Signed written informed consent prior to the performance of any trial specific procedure

Exclusion Criteria:

* History of previous or concurrent (i.e., second primary) invasive melanoma
* Primary melanoma of the eye, mucous membranes or internal viscera
* Any additional solid tumor or hematologic malignancy during the past 5 years except skin lesions of squamous cell carcinoma, basal cell carcinoma, or uterine cervical cancer
* Skin grafts, tissue transfers or flaps that have the potential to alter the lymphatic drainage pattern from the primary melanoma to a lymph node basin
* Hypersensitivity to the active substance(s), to any of the excipients or to any of the components of the labelled radiopharmaceutical
* Extensive previous surgery in the region of the primary tumor site or complete lymph node dissection (CLNDs) or sentinel lymphadenectomy (SLs) (before evaluation of the current melanoma) that may have altered the lymphatic drainage pattern from the primary cutaneous melanoma to a potential lymph node basin
* Organic brain syndrome or significant impairment of basal cognitive function or any psychiatric disorder that might preclude participation in the full protocol, or be exacerbated by therapy (e.g., severe depression)
* Pregnancy (absence to be confirmed by ß-human chorionic gonadotropin test) or lactation period
* Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent
* Known alcohol or drug abuse
* Participation in another clinical study within the 30 days before registration
* Significant disease which, in the investigator's opinion, would exclude the patient from the study
* Legal incapacity or limited legal capacity

Primary outcomes:
measure: Distant free metastasis survival (DFMS)
timeFrame: 6 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 6 years
measure: Disease-free survival (DFS)
timeFrame: 6 years
measure: False negative rate of SLN
timeFrame: 3 years
measure: Sensitivity
timeFrame: 3 years
measure: Complication rate
timeFrame: 6 years
measure: Quality of Life (QoL)
timeFrame: 6 years
measure: Quality adjusted life years (QALY)
timeFrame: 6 years
measure: Number of inpatient days
timeFrame: 6 years
measure: Overall costs during hospital stays
timeFrame: 6 years
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 6 years
Other outcomes:
Locations:
city: Essen
country: Germany
facility: Department of Dermatology, University Hospital Essen
state: NRW
city: Augsburg
country: Germany
facility: Hospital Augsburg, Department of Dermatology
city: Berlin
country: Germany
facility: Vivantes Hospital Berlin Neukölln
city: Bonn
country: Germany
facility: University Hospital Bonn
city: Dresden
country: Germany
facility: Hospital Dresden Friedrichstadt, Department of Dermatology and Allergology
city: Dresden
country: Germany
facility: Universitätsklinik Dresden
city: Düsseldorf
country: Germany
facility: Universitätskliniken Düsseldorf
city: Giessen
country: Germany
facility: Universitätsklinikum Giessen
city: Göttingen
country: Germany
facility: University Hospital Göttingen, Department of Dermatology
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg, Department of Dermatology
city: Lübeck
country: Germany
facility: University Hospital Lübeck, Department of Dermatology
city: Tübingen
country: Germany
facility: University Hospital Tübingen
Study officials:
affiliation: Department of Dermatology, University Hospital Essen
name: Ingo Stoffels, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Dermatology, University Hospital Essen
name: Joachim Klode, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stoffels I, Herrmann K, Rekowski J, Jansen P, Schadendorf D, Stang A, Klode J. Sentinel lymph node excision with or without preoperative hybrid single-photon emission computed tomography/computed tomography (SPECT/CT) in melanoma: study protocol for a multicentric randomized controlled trial. Trials. 2019 Feb 4;20(1):99. doi: 10.1186/s13063-019-3197-7.