The Combination of Anti-PD-1 With Radiotherapy in Previously Untreated Metastatic Melanoma
1 other identifier
interventional
52
1 country
1
Brief Summary
Currently, the first line treatment options for surgically unresectable metastatic melanoma includes anti-PD1 agents such as nivolumab and pembrolizumab. In western countries, UV associated cutaneous melanoma has 30-40% response rates to immune checkpoint inhibitors (ICIs). However, response rates are lower in Asians. The reason for this discrepancy is attributed to the difference in subtypes since most of the Asian patients are mostly subgrouped as acral lentiginous or mucosal types that are unrelated to UV exposures. Thus, there is an unmet need to bolster the effect of ICIs in these patients. The combination of radiotherapy with ICIs have been demonstrated by several pre-clinical studies. High dose radiation has shown to promote STING pathway which activates dendritic cells needed in priming phase. In addition, low dose radiation may activate macrophage differentiation. These mechanisms in turn may enhance responses to immunotherapy. In this study, the investigators aim to evaluate the efficacy and tolerability of anti-PD-1 blockade in combination with radiotherapy in surgically unresectable, treatment naive metastatic melanoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jul 2019
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 3, 2019
CompletedFirst Submitted
Initial submission to the registry
July 8, 2019
CompletedFirst Posted
Study publicly available on registry
July 12, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2022
CompletedJuly 12, 2019
July 1, 2019
3 years
July 8, 2019
July 10, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Overall response rate (ORR)
assessment of efficacy of anti-PD1 with radiotherapy in terms of overall response rate (ORR)
1 year
Secondary Outcomes (4)
treatment-related adverse events (TRAE)
3 years
rate of progression-free survival (PFS)
1 year
overall survival (OS)
1 year
disease control rate (DCR)
1 year
Study Arms (1)
Experimental
EXPERIMENTALInterventions
Subjects with treatment naïve, surgically unresectable metastatic melanoma stages IIIB to IVM1c will be treated with combination of anti-PD1 (pembrolizumab or nivolumab) and radiotherapy.
Eligibility Criteria
You may qualify if:
- \. Subject has provided informed consent prior to initiation of any study-specific activities/procedures
- \. Male or female age \> 20 years at the time of informed consent
- \. Histologically confirmed diagnosis of unresectable stage III or IV melanoma as per AJCC staging system 8th edition
- \. Subject with no prior systemic treatment
- \. Eastern Cooperative Oncology Group (ECOG) Performance Status \< 1
- \. Screening labs performed within 7 days of randomization demonstrating adequate hematologic, coagulation, liver, and kidney functions
- \. Indications for radiotherapy
- \. BRAF status must be checked, but patient is eligible regardless of BRAF mutations (BRAF V600 wild type or BRAF V600 mutation positive are both eligible)
You may not qualify if:
- \. Ocular melanoma
- \. Active brain metastasis (stable after 1 month of radiotherapy, gamma knife surgery or surgery)
- \. Requires palliative radiotherapy
- \. Previous treatment with chemotherapy, a CTLA-4 or PD-1/PD-L1 antagonist agent, including treatment in adjuvant setting
- \. Concurrent medical disease which would significantly limit full compliance with the study such as, but not limited to the following: heart failure (III, IV as per NYHA classification), renal insufficiency, active infection (requires negative gest for clinically suspected HIV, hepatitis B virus, hepatitis C virus).
- If positive results are not indicative of true active or chronic infection, the subject may enter the study after discussion and agreement between the investigator and medical director.
- \. Has known malignancy that is progressing and requires active treatment
- \. Has known psychiatric or substance abuse disorders that would interfere with cooperation requirements of the trial
- \. Lack of availability for clinical follow-up assessments
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Department of Surgery, Yonsei University College of Medicine
Seoul, 120-752, South Korea
Related Publications (2)
Lee J, Chang JS, Roh MR, Jung M, Lee CK, Oh BH, Chung KY, Koom WS, Shin SJ. Clinical Outcomes of Immune Checkpoint Blocker Therapy for Malignant Melanoma in Korean Patients: Potential Clinical Implications for a Combination Strategy Involving Radiotherapy. Cancer Res Treat. 2020 Jul;52(3):730-738. doi: 10.4143/crt.2019.598. Epub 2020 Feb 13.
PMID: 32054150DERIVEDKim HJ, Chang JS, Roh MR, Oh BH, Chung KY, Shin SJ, Koom WS. Effect of Radiotherapy Combined With Pembrolizumab on Local Tumor Control in Mucosal Melanoma Patients. Front Oncol. 2019 Sep 4;9:835. doi: 10.3389/fonc.2019.00835. eCollection 2019.
PMID: 31552171DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 8, 2019
First Posted
July 12, 2019
Study Start
July 3, 2019
Primary Completion
July 1, 2022
Study Completion
July 1, 2022
Last Updated
July 12, 2019
Record last verified: 2019-07