Surgery of Melanoma Metastases After Systemic Therapy

Study Overview
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Brief Summary
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To evaluate if surgical removal of residual disease adds benefit in stage IV melanoma patients with partial response or stable disease after a minimum 9 months of first-line PD-1 inhibition. Primary endpoint: Disease-free survival (DFS) at 12 months.

Detailed Description
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A Phase II Randomized Controlled Open-Label Parallel Group Interventional Multicenter Trial. Patients with metastatic melanoma, stratified for stage M1a or M1b/M1c, that have received first-line treatment with PD-1 inhibitors for a minimum of 9 months resulting in either partial response or stable disease according to RECIST 1.1 will be eligible. Patients will be screened for operability based on CT-scans examined by a multidisciplinary team, with the criteria that complete (R0) resection of all metastases should be possible. If the multidisciplinary team find that this would be possible, patients will be included and randomized 1:1 to either surgery with continued PD1-inhibition or current standard of care with continued PD1-inhibition only. At progression, treatment will be according to the treating medical oncologist. Active follow-up will be performed for 12 months.

Official Title
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Surgery of Melanoma Metastases After Systemic Therapy - the SUMMIST Trial

Conditions
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Melanoma, Melanoma Stage IV, Metastatic Melanoma, Surgery

Intervention / Treatment
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* Procedure: Surgical metastasectomy
* Drug: Immunotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age above 18 years Signed and dated written informed consent before the start of specific protocol procedures Biopsy or cytology proven metastatic melanoma stage M1a, M1b or M1c Have received a minimum of 9 months of immunotherapy (PD1-inhibitor alone or in combination) resulting in stable disease or partial response according to RECIST 1.1 Metastases judged to be radically resectable by surgery at a multidisciplinary conference ECOG performance status 0-2 Exclusion Criteria: Brain metastasis (M1d) Previous treatment with BRAF/MEK inhibitors Inability to understand given information or undergo study procedures according to protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Phase II Randomized Controlled Open-Label Parallel Group Interventional Multicenter Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD1-inhibitor + surgery<br>Patients randomised to the interventional study arm, receiving both surgical metastasectomy and continued immunotherapy. Each patient case will be individually planned for surgery. Procedures will include, but will not be limited to, lung resections, liver resections, bowel resection, skin excisions and lymph node clearances. Patients in both study arms will continue with PD-1 inhibitor 12 months after randomization, and will then be treated according to their medical oncologist. | Procedure: Surgical metastasectomy<br>* Surgical removal of metastases aimed at R0 resection.<br>|
| Active Comparator: PD1-inhibitor<br>Patients randomized to control study arm, receiving continued immunotherapy only. Patients in both study arms will continue with PD-1 inhibitor 12 months after randomization, and will then be treated according to their medical oncologist. | Drug: Immunotherapy<br>* Continued PD1-inhibitor treatment according to current treatment standards.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DFS 12 months | Disease free survival | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAE 12 months | Serious adverse events | 12 months | 
| Complications | Surgical complications according to the Clavien-Dindo classification | 3 months post operatively | 
| R0 resection | Rate of R0 resections according to pathology report | 3 months post operatively | 
| PFS 12 months | Progression free survival | 12 months | 
| MSS 12 months | Melanoma specific survival | 12 months | 
| OS 12 months | Overall survival | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, Metastatic surgery, Surgical oncology