Surgery of Melanoma Metastases After Systemic Therapy

Phase 2

Withdrawn

• Conditions: Melanoma; Metastatic Melanoma; Melanoma Stage IV; Surgery
• Interventions: Procedure: Surgical metastasectomy; Drug: Immunotherapy

• Registration Number: NCT04242329
• Lead Sponsor: Vastra Gotaland Region

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-01-23
• Study First Submitted QC: 2020-01-23
• Study First Posted: 2020-01-27
• Study Start: 2021-03-11
• Primary Completion: 2023-09-03
• Study Completion: 2023-09-13
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-25
• Last Update Posted: 2024-01-26

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PD1-inhibitor + surgery	Surgical metastasectomy	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.
PD1-inhibitor	Immunotherapy	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.

Primary Outcome Measures

Name	Time	Method
DFS 12 months	12 months	Disease free survival

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Sahlgrenska University Hospital; 🇸🇪 Gothenburg, Sweden