MelanomaPhase 2PERMNCT02562625
Trial of Pembrolizumab and Radiotherapy in Melanoma
A Phase 2 study testing Pembrolizumab and Radiotherapy in people with Melanoma, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Around 13,000 participants are diagnosed with melanoma in the UK each year and that number is growing quicker than any other cancer. About 20% of participants will see their cancer return following their initial treatment and at present would survive a median time of 912 months. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Pembrolizumab and Radiotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 11 Aug 2016to Oct 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent for the trial
- Have a diagnosis of stage III (unresectable) or stage IV cutaneous melanoma or melanoma of unknown primary, as per AJCC staging system
- Informed metastatic disease by diagnostic biopsy
- Be more than 18 years of age on day of signing informed consent
- Have at least one lesion and a maximum of 3 which are appropriate targets for high dose radiotherapy. This lesion must be 1cm-5cm in size and measurable by RECIST v1.1
- Have in addition at least one other lesion which will not be irradiated but must be measurable by RECIST v1.1 to assess the abscopal effect of the treatment
Show all 11Show fewer
- Have a performance status of 0 or 1 on the ECOG performance scale
- Demonstrate adequate organ function as defined in table 1 below. All screening labs should be performed within 7 days of randomisation
- Female patient of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to randomisation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
- Male patients should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
Who cannot join
- Has lesions that if irradiated would result in unacceptable radiation induced toxicity to normal tissue, in particular to the CNS and bowel
- Requires palliative radiotherapy for symptom control
- Is currently participating in or has participated in a study of an investigational agent or device within 4 weeks of the first dose of trial treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has had a monoclonal antibody within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e. ≤Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
- Has had chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤Grade 1 or at baseline) from adverse events due to a previously administered agent
Show all 21Show fewer
- Note: patients with an AE ≤Grade 2 neuropathy are an exception to this criterion and may qualify for the study
- Note: if patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Has history of severe colitis related to previous immunotherapy treatment
- Has a known additional malignancy that is progressing or requires active treatment Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Has known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA [qualitative] is detected)
- Has received a live vaccine within 30 days prior to the first dose of trial treatment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomised Phase II Trial of Pembrolizumab and Radiotherapy in Melanoma
Around 13,000 participants are diagnosed with melanoma in the UK each year and that number is growing quicker than any other cancer. About 20% of participants will see their cancer return following their initial treatment and at present would survive a median time of 912 months. In recent years, the development of new effective drugs has revolutionised the treatment of advanced melanoma, However, response rates are still low and new therapeutic approaches are needed.
This is a phase II study to look at the effectiveness and safety of the combination of a new drug called pembrolizumab plus radiotherapy compared to pembrolizumab alone. The purpose of this study is to see if the addition of radiotherapy to pembrolizumab is better than pembrolizumab alone by measuring how long these treatments can control the growth of the cancer. Also it will assess if by adding radiotherapy the investigators can see its effects not only in the tumour that has had radiotherapy but also in other tumours in the rest of the body.
Read the detailed description
- Risk and burden for participants Participants in this study have cancer but may still be eligible for standard therapy and may not show any benefit from the trial drug. If this is the case will be withdrawn from the trial and will receive standard care. The study itself carries a number of potential burdens:
- Study drug and Radiotherapy. Although the dose and safety effects of the drug have been previously assessed in phase I trials and the radiotherapy used is considered standard of care, it is possible for participants to experience some side effects. To ensure any side effects are treated appropriately all participants will be reviewed regularly by experienced clinicians while having the study treatment. Comprehensive assessments for safety will be carried out.
- Burden of frequent hospital visits and tests. Participants in this study must attend hospital every 3 weeks to check for any side effects of the drug, have routine blood and clinical biochemistry tests, clinical examinations and administer the next dose of pembrolizumab. Additionally, for research purposes some participants may consent to have additional tumour biopsies and blood tests. These will not be mandatory for all participants.
- Recruitment Participants will be offered information about this study by their clinical teams if they are considered to meet the entry criteria and express interest in taking part in the study. It will be made clear that there will not necessarily be a therapeutic benefit from taking part in the study. It will also be made clear that, should participants decide not to take part their future care will not be affected. Participants will be given sufficient time and information to make an informed decision about entering the trial, all participants entering the trial will give written informed consent.
- Confidentiality Participants will be linked to a unique identifier the code for which will be held on a password protected database held only by the study team. This study will run across twenty two hospital sites. Tumour data will be analysed at Manchester University and research blood will be analysed at Leeds University. Sample processing will take place using the trial ID only. No other patient identifiable information will be available on study samples. Investigators will have access to patient identifiable information on password protected NHS hospital notes and databases only.
- Conflict of Interest Participants may be recruited to the study by those involved in their prior clinical care. Investigators do not expect conflict of interest between research and healthcare duties for a number of reasons: participants must give their full informed consent before entering the study, specifically regarding the unknown efficacy of the study drug. Those participants who do not continue in the study will maintain a relationship with the clinical team if required for symptom control. At the end of the study, participants will be able to access the results if they wish, through the Royal Marsden Website. They will also be sent a written summary of the results if they indicate this.
- Use of tissue samples in future research If participants give their consent, any leftover blood or tissue samples which are not required for this study will be stored for future unspecified research in line with the human tissue act regulations. Access and use of samples for research purposes will require appropriate ethical approval. Future researchers will not be able to identify individual participants from their biobank data, demographic and clinical information will be available.
- Conditions
- Melanoma
- Being tested
- Pembrolizumab, Radiotherapy
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Powder solution for infusion
RadiotherapyRadiation
24Gy
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab Alone | Experimental | If the patient is randomised to the Pembrolizumab Arm Only then they will receive 200mg of pembrolizumab every 3 weeks. Receives: Drug: Pembrolizumab |
| Pembrolizumab plus Radiotherapy | Experimental | If The patient is randomised to this arm they will receive 200mg of pembrolizumab every 3 weeks in combination with a radiotherapy dosage of 24Gy in 3 fractions to be given over 3 consecutive days (only). Receives: Drug: Pembrolizumab; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective: To Evaluate if Radiotherapy Will Enhance the Efficacy of Pembrolizumab in the Treatment of Patients With Metastatic Melanoma by Induction of an Abscopal Effect.
Percentage of patients with improved tumour response rate (CR/PR) according to the RECIST v1.1 criteria at 12 weeks post treatment start date with the combination therapy of pembrolizumab plus radiotherapy.
Measured: From date of randomisation until week 12 from start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2015 (estimated)
- Study start11 Aug 2016
- Primary completionMar 2020
- Study completionOct 2021
Why it stopped: Slow Recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Royal Marsden NHS Foundation TrustThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Manchester, University of Leeds
- Responsible party
- Sponsor
- Investigators
- James Larkin, MD, Study director, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02562625
- Sponsor's protocol ID
- CCR 4251
- Acronym
- PERM
- Status last verified
- Apr 2026
- First submitted
- 7 Sep 2015
- Last updated
- 23 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Phase II Trial of Pembrolizumab and Radiotherapy in Melanoma
- ClinicalTrials.gov ID
- NCT02562625
- Acronym / sponsor ID
- PERM / CCR 4251
- Conditions
- Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow Recruitment
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Manchester, University of Leeds
- Study start
- 11 Aug 2016 (actual)
- Primary completion
- Mar 2020 (actual)
- Study completion
- Oct 2021 (actual)
- First posted
- 29 Sep 2015 (estimated)
- Results
- Posted 23 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Around 13,000 participants are diagnosed with melanoma in the UK each year and that number is growing quicker than any other cancer. About 20% of participants will see their cancer return following their initial treatment and at present would survive a median time of 912 months. In recent years, the development of new effective drugs has revolutionised the treatment of advanced melanoma, However, response rates are still low and new therapeutic approaches are needed.
This is a phase II study to look at the effectiveness and safety of the combination of a new drug called pembrolizumab plus radiotherapy compared to pembrolizumab alone. The purpose of this study is to see if the addition of radiotherapy to pembrolizumab is better than pembrolizumab alone by measuring how long these treatments can control the growth of the cancer. Also it will assess if by adding radiotherapy the investigators can see its effects not only in the tumour that has had radiotherapy but also in other tumours in the rest of the body.
Detailed description
- Risk and burden for participants Participants in this study have cancer but may still be eligible for standard therapy and may not show any benefit from the trial drug. If this is the case will be withdrawn from the trial and will receive standard care. The study itself carries a number of potential burdens:
- Study drug and Radiotherapy. Although the dose and safety effects of the drug have been previously assessed in phase I trials and the radiotherapy used is considered standard of care, it is possible for participants to experience some side effects. To ensure any side effects are treated appropriately all participants will be reviewed regularly by experienced clinicians while having the study treatment. Comprehensive assessments for safety will be carried out.
- Burden of frequent hospital visits and tests. Participants in this study must attend hospital every 3 weeks to check for any side effects of the drug, have routine blood and clinical biochemistry tests, clinical examinations and administer the next dose of pembrolizumab. Additionally, for research purposes some participants may consent to have additional tumour biopsies and blood tests. These will not be mandatory for all participants.
- Recruitment Participants will be offered information about this study by their clinical teams if they are considered to meet the entry criteria and express interest in taking part in the study. It will be made clear that there will not necessarily be a therapeutic benefit from taking part in the study. It will also be made clear that, should participants decide not to take part their future care will not be affected. Participants will be given sufficient time and information to make an informed decision about entering the trial, all participants entering the trial will give written informed consent.
- Confidentiality Participants will be linked to a unique identifier the code for which will be held on a password protected database held only by the study team. This study will run across twenty two hospital sites. Tumour data will be analysed at Manchester University and research blood will be analysed at Leeds University. Sample processing will take place using the trial ID only. No other patient identifiable information will be available on study samples. Investigators will have access to patient identifiable information on password protected NHS hospital notes and databases only.
- Conflict of Interest Participants may be recruited to the study by those involved in their prior clinical care. Investigators do not expect conflict of interest between research and healthcare duties for a number of reasons: participants must give their full informed consent before entering the study, specifically regarding the unknown efficacy of the study drug. Those participants who do not continue in the study will maintain a relationship with the clinical team if required for symptom control. At the end of the study, participants will be able to access the results if they wish, through the Royal Marsden Website. They will also be sent a written summary of the results if they indicate this.
- Use of tissue samples in future research If participants give their consent, any leftover blood or tissue samples which are not required for this study will be stored for future unspecified research in line with the human tissue act regulations. Access and use of samples for research purposes will require appropriate ethical approval. Future researchers will not be able to identify individual participants from their biobank data, demographic and clinical information will be available.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab Alone | Experimental | Drug: PembrolizumabIf the patient is randomised to the Pembrolizumab Arm Only then they will receive 200mg of pembrolizumab every 3 weeks. |
| Pembrolizumab plus Radiotherapy | Experimental | Drug: Pembrolizumab, Radiation: RadiotherapyIf The patient is randomised to this arm they will receive 200mg of pembrolizumab every 3 weeks in combination with a radiotherapy dosage of 24Gy in 3 fractions to be given over 3 consecutive days (only). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Be willing and able to provide written informed consent for the trial
- Have a diagnosis of stage III (unresectable) or stage IV cutaneous melanoma or melanoma of unknown primary, as per AJCC staging system
- Informed metastatic disease by diagnostic biopsy
- Be more than 18 years of age on day of signing informed consent
- Have at least one lesion and a maximum of 3 which are appropriate targets for high dose radiotherapy. This lesion must be 1cm-5cm in size and measurable by RECIST v1.1
Key exclusion criteria (21 listed)
- Has lesions that if irradiated would result in unacceptable radiation induced toxicity to normal tissue, in particular to the CNS and bowel
- Requires palliative radiotherapy for symptom control
- Is currently participating in or has participated in a study of an investigational agent or device within 4 weeks of the first dose of trial treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has had a monoclonal antibody within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e. ≤Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
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 |
|---|---|---|
| PembrolizumabPowder solution for infusion | Drug | Pembrolizumab Alone, Pembrolizumab plus Radiotherapy |
| Radiotherapy24Gy | Radiation | Pembrolizumab plus Radiotherapy |
Primary outcome
Objective: To Evaluate if Radiotherapy Will Enhance the Efficacy of Pembrolizumab in the Treatment of Patients With Metastatic Melanoma by Induction of an Abscopal Effect.
Time frame: From date of randomisation until week 12 from start of treatment
Percentage of patients with improved tumour response rate (CR/PR) according to the RECIST v1.1 criteria at 12 weeks post treatment start date with the combination therapy of pembrolizumab plus radiotherapy.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Melanoma
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.
James Larkin, MD study director
Royal Marsden NHS Foundation Trust
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 Pembrolizumab and Radiotherapy in people with Melanoma, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
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 11 inclusion and 21 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: stopped early, as of the sponsor's last update on 23 Apr 2026. 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 United Kingdom. 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?
Yes. Results are posted in the registry (first posted 23 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective: To Evaluate if Radiotherapy Will Enhance the Efficacy of Pembrolizumab in the Treatment of Patients With Metastatic Melanoma by Induction of an Abscopal Effect. (time frame: From date of randomisation until week 12 from start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Apr 2026.