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

Primary Purpose

Melanoma

Status

Unknown status

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

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

About this trial

This is an interventional treatment trial for Melanoma

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Department of Surgery, Yonsei University College of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental

Arm Description

Outcomes

Primary Outcome Measures

Overall response rate (ORR)

assessment of efficacy of anti-PD1 with radiotherapy in terms of overall response rate (ORR)

Secondary Outcome Measures

treatment-related adverse events (TRAE)

rate of progression-free survival (PFS)

overall survival (OS)

disease control rate (DCR)

Full Information

NCT ID

NCT04017897

First Posted

July 8, 2019

Last Updated

July 10, 2019

Sponsor

Yonsei University

1. Study Identification

Unique Protocol Identification Number

NCT04017897

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Unknown status

Study Start Date

July 3, 2019 (Actual)

Primary Completion Date

July 2022 (Anticipated)

Study Completion Date

July 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yonsei University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

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

Intervention Description

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.

Primary Outcome Measure Information:

Title

Overall response rate (ORR)

Description

assessment of efficacy of anti-PD1 with radiotherapy in terms of overall response rate (ORR)

Time Frame

1 year

Secondary Outcome Measure Information:

Title

treatment-related adverse events (TRAE)

Time Frame

3 years

Title

rate of progression-free survival (PFS)

Time Frame

1 year

Title

overall survival (OS)

Time Frame

1 year

Title

disease control rate (DCR)

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sang Joon Shin, MD, Ph.D

Phone

82-2-2228-8138

ssj338@yuhs.ac

Facility Information:

Facility Name

Department of Surgery, Yonsei University College of Medicine

City

Seoul

ZIP/Postal Code

120-752

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sang-Joon Shin, MD, Ph.D

Phone

82-2-2228-8138

ssj338@yuhs.ac

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

32054150

Citation

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.

Results Reference

derived

PubMed Identifier

31552171

Citation

Kim 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.

Results Reference

derived

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

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