Clinical Trials /

The Combination of Anti-PD-1 With Radiotherapy in Previously Untreated Metastatic Melanoma

NCT04017897

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: The Combination of Anti-PD-1 With Radiotherapy in Previously Untreated Metastatic Melanoma
  • Official Title: The Combination of Anti-PD-1 With Radiotherapy in Previously Untreated Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 4-2019-0461
  • NCT ID: NCT04017897

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
The combination of radiotherapy with anti-PD1 (pembrolizumab or nivolumab)Experimental

Purpose

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 Arms

NameTypeDescriptionInterventions
ExperimentalExperimental
  • The combination of radiotherapy with anti-PD1 (pembrolizumab or nivolumab)

Eligibility Criteria

        Inclusion Criteria:

          -  1. Subject has provided informed consent prior to initiation of any study-specific
             activities/procedures

          -  2. Male or female age > 20 years at the time of informed consent

          -  3. Histologically confirmed diagnosis of unresectable stage III or IV melanoma as per
             AJCC staging system 8th edition

          -  4. Subject with no prior systemic treatment

          -  5. Eastern Cooperative Oncology Group (ECOG) Performance Status < 1

          -  6. Screening labs performed within 7 days of randomization demonstrating adequate
             hematologic, coagulation, liver, and kidney functions

          -  7. Indications for radiotherapy

          -  8. 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)

        Exclusion Criteria:

          -  1. Ocular melanoma

          -  2. Active brain metastasis (stable after 1 month of radiotherapy, gamma knife surgery
             or surgery)

          -  3. Requires palliative radiotherapy

          -  4. Previous treatment with chemotherapy, a CTLA-4 or PD-1/PD-L1 antagonist agent,
             including treatment in adjuvant setting

          -  5. Autoimmune disease requiring chronic treatment with systemic corticosteroids or any
             other immunosuppressive agents 7 days prior to inclusion. (physiologic dose of
             prednisolone 10mg or equivalent are accepted)

          -  6. 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.

          -  7. Has known malignancy that is progressing and requires active treatment

          -  8. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation requirements of the trial

          -  9. Lack of availability for clinical follow-up assessments
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:1 year
Safety Issue:
Description:assessment of efficacy of anti-PD1 with radiotherapy in terms of overall response rate (ORR)

Secondary Outcome Measures

Measure:treatment-related adverse events (TRAE)
Time Frame:3 years
Safety Issue:
Description:
Measure:rate of progression-free survival (PFS)
Time Frame:1 year
Safety Issue:
Description:
Measure:overall survival (OS)
Time Frame:1 year
Safety Issue:
Description:
Measure:disease control rate (DCR)
Time Frame:1 year
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Yonsei University

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