A phase II double-blind placebo-controlled randomized trial. Patients with a clinical suspicion of a thick primary melanoma without clinical suspicion or evidence of lymph-node engagement will undergo a 3 mm punch biopsy to verify the diagnosis and ascertain eligibility. Patients will receive 1 cycle of pembrolizumab 400 mg or placebo and 4 weeks later undergo a wide local excision and sentinel lymph node biopsy according to the national guideline recommendations . The primary objective is to evaluate the pathological response of one cycle of neoadjuvant pembrolizumab in patients with biopsy-proven stage IIb/c melanoma. Secondary objectives include efficacy and safety analysis, as well as biomarker discovery.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
30
Immunotherapy
Placebo
Sahlgrenska University Hospital
Gothenburg, Sweden
RECRUITINGPathological response rate
Pathological response rate in the primary tumor according to adapted guidelines of the International Neoadjuvant Consortium (14) The pathological response will be described: * Complete pathological response (pCR) - 0% viable tumor cells in the surgical specimen * Near complete pathological response (near pCR) - ≤10% viable tumor * Partial pathological response (pPR) - \>10%-≤50% viable tumor * No pathological response (pNR) - \>50% viable tumor The proportion of patients with a pCR, near pCR or pPR will determine the pathological response rate.
Time frame: 48 month
Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)
The proportion of patients with adverse events (AE) as described in CTCAE version 5.0, from the initiation of study treatment until 100 days after the end of treatment: 1. Proportion of patients with an AE by CTCAE term and grade. 2. Proportion of patients with grade 3/4 AEs by AE term. 3. The duration of events reported in (a) 4. Proportion of patients with requirement to delay surgery due to an AE. 5. Proportion of patients with a requirement to permanently discontinue study treatment due to an AE. 6. The proportion of patients with a requirement for oral or parenteral steroid treatment for immunology-related adverse events. 7. The proportion of patients with post-operative complications (e.g. seroma formation, wound infection or lymphoedema) and duration of events.
Time frame: 48 month
Feasibility of neoadjuvant therapy in stage II melanoma
1. Proportion of eligible patients who consent to the study. 2. Proportion of included patients who complete all treatment according to protocol.
Time frame: 48 month
Sentinel lymph node positivity rate
1. The proportion of patients undergoing a sentinel node biopsy who have a positive result in the lymph node. 2. The number of sentinel nodes identified and the number harvested. 3. The proportion of patients with a positive sentinel node biopsy who undergo completion lymph node dissection.
Time frame: 48 month
Local recurrence rate
The proportion of patients after surgery with histologically confirmed diagnosis of local disease recurrence, as detected by the patient, on physical examination or during imaging surveillance.
Time frame: 48 month
Regional recurrence rate
The proportion of patients after surgery with histologically confirmed diagnosis of regional disease recurrence, as detected by the patient, on physical examination or during imaging surveillance
Time frame: 48 month
Event free survival (EFS)
The proportion of patients that did not undergo surgery or histologically confirmed diagnosis of disease recurrence (local, regional, and distant), as detected by the patient, on physical examination or during imaging surveillance, or death from any cause.
Time frame: 48 month
To assess recurrence free survival (RFS).
The proportion of patients after surgery with histologically confirmed diagnosis of disease recurrence (local, regional, and distant), as detected by the patient, on physical examination or during imaging surveillance, or death from any cause.
Time frame: 48 month
Distant metastasis-free survival (DMFS)
The proportion of patients after surgery with histologically confirmed diagnosis of disease distant recurrence, as detected by the patient, on physical examination or during imaging surveillance, or death from any cause.
Time frame: 48 month
Melanoma specific survival (MSS)
The proportion of patients who die, from the initiation of study treatment to the date of death from melanoma.
Time frame: 48 month
Overall survival (OS)
The proportion of patients who die, from the initiation of study treatment to the date of death from any cause.
Time frame: 48 month
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.