MelanomaPhase 2NCT04017897
The Combination of Anti-PD-1 With Radiotherapy in Previously Untreated Metastatic Melanoma
A Phase 2 study testing The combination of radiotherapy with anti-PD1 (pembrolizumab or nivolumab) in people with Melanoma, run by Yonsei University at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Melanoma
- What is being tested?
- The combination of radiotherapy with anti-PD1 (pembrolizumab or nivolumab)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteSouth Korea
- Study dates
- 3 Jul 2019to Jul 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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).
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- 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
Trial locations and contacts
1 site in 1 country.
South Korea1 site, 1 recruiting
- Recruiting
Department of Surgery, Yonsei University College of Medicine
Seoul, 120-752
Sang-Joon Shin, MD, Ph.D, 82-2-2228-8138, ssj338@yuhs.ac
About this study
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.
- Conditions
- Melanoma
- Being tested
- The combination of radiotherapy with anti-PD1 (pembrolizumab or nivolumab)
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The combination of radiotherapy with anti-PD1 (pembrolizumab or nivolumab)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Not described Receives: Drug: The combination of radiotherapy with anti-PD1 (pembrolizumab or nivolumab) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR)
assessment of efficacy of anti-PD1 with radiotherapy in terms of overall response rate (ORR)
Measured: 1 year
Secondary outcomes (4)
treatment-related adverse events (TRAE)
Measured: 3 years
rate of progression-free survival (PFS)
Measured: 1 year
overall survival (OS)
Measured: 1 year
disease control rate (DCR)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2019
- Study start3 Jul 2019
- Primary completionJul 2022 (estimated)
- Study completionJul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04017897
- Sponsor's protocol ID
- 4-2019-0461
- Status last verified
- Jul 2019
- First submitted
- 8 Jul 2019
- Last updated
- 12 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 32054150Kim 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.
PubMed 31552171
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Combination of Anti-PD-1 With Radiotherapy in Previously Untreated Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT04017897
- Acronym / sponsor ID
- 4-2019-0461
- Conditions
- Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 3 Jul 2019 (actual)
- Primary completion
- Jul 2022 (estimated)
- Study completion
- Jul 2022 (estimated)
- First posted
- 12 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: The combination of radiotherapy with anti-PD1 (pembrolizumab or nivolumab) |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| The combination of radiotherapy with anti-PD1 (pembrolizumab or nivolumab)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. | Drug | Experimental |
Primary outcome
Overall response rate (ORR)
Time frame: 1 year
assessment of efficacy of anti-PD1 with radiotherapy in terms of overall response rate (ORR)
4 secondary outcomes
treatment-related adverse events (TRAE)
Time frame: 3 years
rate of progression-free survival (PFS)
Time frame: 1 year
overall survival (OS)
Time frame: 1 year
disease control rate (DCR)
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2019.
- Derived from this study: PubMed 32054150Lee 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.
- Derived from this study: PubMed 31552171Kim 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing The combination of radiotherapy with anti-PD1 (pembrolizumab or nivolumab) in people with Melanoma, run by Yonsei University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sang Joon Shin, MD, Ph.D (82-2-2228-8138, ssj338@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04017897, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2019.