Metastatic MelanomaPROMMELNCT04793737
Precision Radiation of Immune Checkpoint Therapy Resistant Melanoma Metastases
A study testing Precision Radiation (SBRT) in people with Metastatic Melanoma, run by Karolinska University Hospital at 1 site in Sweden.
Trial summary
To evaluate tumor response, survival and adverse effects after precision radiotherapy (SBRT) in melanoma patients with ongoing PD-1 inhibitor treatment that have tumor progression. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- Precision Radiation (SBRT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteSweden
- Study dates
- 8 Mar 2021to Dec 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Age 18 and above
- ECOG performance status of 0-1
- Signed and dated written informed consent before the start of specific protocol procedures.
- Patient has initiated PD-1 inhibitor treatment (alone or in combination with CTLA-4 inhibitor) as the first line of therapy for unresectable metastatic cutaneous melanoma and been on the treatment for at least 3 months and progressed on the treatment. Patients with primary or secondary resistance to the PD-1 inhibitor treatment will be included. Progression is defined as at least 30% enlargement of at least one metastasis or appearance of new metastasis. A fine-needle aspiration (FNA) biopsy from a progressing lesion or a new lesion is recommended to confirm the presence of viable tumor cells.
- Patients on adjuvant treatment with PD-1 inhibitors that during the treatment develop unresectable biopsy confirmed metastases can also be included in the study.
- Have at least one new or progressing lesion safely amenable to irradiation in the opinion of the treating radiation oncologist AND at least one, not-to-be-irradiated new or progressing lesion measurable by CT or MRI per RECIST 1.1 criteria where up to four radiation target fields are allowed
- No contraindication for continuing immunotherapy after the radiotherapy intervention
Who cannot join
- Inability to understand given information or undergo study procedures according to protocol
- Pregnant or breast-feeding. Patients must agree to use safe contraception during and for 3 months after study treatment.
- A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 30 days before start of study treatment. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted.
- Has an active infection requiring systemic therapy.
- Concomitant therapy with any anti-tumor medications, other than PD-1/CTLA-4 inhibitors or 30 days before and after treatment in this trial.
- Prior radiotherapy preventing the study intervention with precision radiotherapy
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- Location, size or number of metastases is deemed as excessive or not appropriate for precision radiotherapy
- Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or anticonvulsants.
- Prior malignancy. Subjects who have had another malignancy should be disease-free for 5 years, or should have a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Sweden1 site, 1 recruiting
- Recruiting
Division of Head-Neck, Lung and Skin cancers, Theme Cancer, Karolinska University Hospital
Stockholm
Hildur Helgadottir, MD, PhD, +46(0)8 51773415, hildur.helgadottir@sll.se
Hildur Helgadottir, MD, PhD
About this study
To evaluate tumor response, survival and adverse effects after precision radiotherapy (SBRT) in melanoma patients with ongoing PD-1 inhibitor treatment that have tumor progression.
Read the detailed description
A phase II open-label multicenter trial evaluating response rate (RR) in patients receiving precision radiation (SBRT) to melanoma metastasis that have progressed on PD-1 inhibitor therapy. Patients will continue on PD-1 inhibitor therapy (pembrolizumab or nivolumab) for up to one year after completed precision radiation and will be followed-up for 24 months or until disease progression or death. The primary endpoint of the study is overall response rate (ORR) in non-irradiated lesions. The study will be conducted according to Simon´s two Stage minimax Design. Patients will be enrolled in two batches, first consisting of 13 patients. If no objective responses (complete response (CR) or partial response (PR)) are reported after the first stage, the study is interrupted early for futility. When the 13th patient is recruited, if there is at least one objective response in patient´s non-irradiated lesion(s), the recruitment can proceed into second stage. 14 more patients will then be included up to a total of 27 patients to determine ORR along with the 95% confidence interval. The test result is considered positive when at least 15% of the patients have a confirmed objective response.
- Conditions
- Metastatic Melanoma
- Being tested
- Precision Radiation (SBRT)
- Keywords
- Precision radiation, PD-1 inhibitor, SBRT, Immune Checkpoint Inhibitor
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Precision Radiation (SBRT)Radiation
Precision radiation of melanoma metastases
| Study group | Role | What they receive |
|---|---|---|
| Precision Radiation (SBRT) | Experimental | Precision radiation of melanoma metastases Receives: Radiation: Precision Radiation (SBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR) in non-irradiated lesions
Overall response rate (ORR) in non-irradiated lesions according to RECIST 1.1
Measured: From date of precision radiation start until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 24 months
Secondary outcomes (5)
Median PFS (months)
Median PFS (months) at 6 and 12 months according to RECIST 1.1
Measured: 6 and 12 months
PFS rate (%)
PFS rate (%) at 6 and 12 months according to RECIST 1.1
Measured: 6 and 12 months
Median OS (months)
Median OS (months) at 6 and 12 months according to RECIST 1.1
Measured: 6 and 12 months
Response rate (RR) in the patient's irradiated lesions
Response rate (RR) in the patient's irradiated lesions according to RECIST 1.1
Measured: From radiation start to end of follow-up, progression or death (3, 6, 9, 12, 15, 18, 21, 24 months)
Rate and type of AEs and SAEs on patient level
Adverse Events and Serious Adverse Events
Measured: From precision radiation start to end of follow-up, progression or death, up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2021
- Study start8 Mar 2021
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by Karolinska University HospitalThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase II open-label multicenter trial
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hildur Helgadottir, Karolinska University Hospital
- Investigators
- Signe Friesland, MD, PhD, Study director, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04793737
- Sponsor's protocol ID
- PROMMEL
- Acronym
- PROMMEL
- Status last verified
- Mar 2025
- First submitted
- 17 Feb 2021
- Last updated
- 5 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precision Radiation of Immune Checkpoint Therapy Resistant Melanoma Metastases
- ClinicalTrials.gov ID
- NCT04793737
- Acronym / sponsor ID
- PROMMEL / PROMMEL
- Conditions
- Metastatic Melanoma
- Keywords
- Precision radiation, PD-1 inhibitor, SBRT, Immune Checkpoint Inhibitor
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Karolinska University HospitalUniversity, hospital or other
- Study start
- 8 Mar 2021 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 11 Mar 2021 (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.
To evaluate tumor response, survival and adverse effects after precision radiotherapy (SBRT) in melanoma patients with ongoing PD-1 inhibitor treatment that have tumor progression.
Detailed description
A phase II open-label multicenter trial evaluating response rate (RR) in patients receiving precision radiation (SBRT) to melanoma metastasis that have progressed on PD-1 inhibitor therapy. Patients will continue on PD-1 inhibitor therapy (pembrolizumab or nivolumab) for up to one year after completed precision radiation and will be followed-up for 24 months or until disease progression or death. The primary endpoint of the study is overall response rate (ORR) in non-irradiated lesions. The study will be conducted according to Simon´s two Stage minimax Design. Patients will be enrolled in two batches, first consisting of 13 patients. If no objective responses (complete response (CR) or partial response (PR)) are reported after the first stage, the study is interrupted early for futility. When the 13th patient is recruited, if there is at least one objective response in patient´s non-irradiated lesion(s), the recruitment can proceed into second stage. 14 more patients will then be included up to a total of 27 patients to determine ORR along with the 95% confidence interval. The test result is considered positive when at least 15% of the patients have a confirmed objective response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase II open-label multicenter trial
| Arm | Type | Receives |
|---|---|---|
| Precision Radiation (SBRT) | Experimental | Radiation: Precision Radiation (SBRT)Precision radiation of melanoma metastases |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age 18 and above
- ECOG performance status of 0-1
- Signed and dated written informed consent before the start of specific protocol procedures.
- Patient has initiated PD-1 inhibitor treatment (alone or in combination with CTLA-4 inhibitor) as the first line of therapy for unresectable metastatic cutaneous melanoma and been on the treatment for at least 3 months and progressed on the treatment. Patients with primary or secondary resistance to the PD-1 inhibitor treatment will be included. Progression is defined as at least 30% enlargement of at least one metastasis or appearance of new metastasis. A fine-needle aspiration (FNA) biopsy from a progressing lesion or a new lesion is recommended to confirm the presence of viable tumor cells.
- Patients on adjuvant treatment with PD-1 inhibitors that during the treatment develop unresectable biopsy confirmed metastases can also be included in the study.
Key exclusion criteria (9 listed)
- Inability to understand given information or undergo study procedures according to protocol
- Pregnant or breast-feeding. Patients must agree to use safe contraception during and for 3 months after study treatment.
- A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 30 days before start of study treatment. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted.
- Has an active infection requiring systemic therapy.
- Concomitant therapy with any anti-tumor medications, other than PD-1/CTLA-4 inhibitors or 30 days before and after treatment in this trial.
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 |
|---|---|---|
| Precision Radiation (SBRT)Precision radiation of melanoma metastases | Radiation | Precision Radiation (SBRT) |
Primary outcome
Overall response rate (ORR) in non-irradiated lesions
Time frame: From date of precision radiation start until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 24 months
Overall response rate (ORR) in non-irradiated lesions according to RECIST 1.1
5 secondary outcomes
Median PFS (months)
Time frame: 6 and 12 months
PFS rate (%)
Time frame: 6 and 12 months
Median OS (months)
Time frame: 6 and 12 months
Response rate (RR) in the patient's irradiated lesions
Time frame: From radiation start to end of follow-up, progression or death (3, 6, 9, 12, 15, 18, 21, 24 months)
Rate and type of AEs and SAEs on patient level
Time frame: From precision radiation start to end of follow-up, progression or death, up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2025.
- Individual participant dataSharing planned: No
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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.
Signe Friesland, MD, PhD study director
Karolinska University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Precision Radiation (SBRT) in people with Metastatic Melanoma, run by Karolinska University Hospital at 1 site in Sweden.
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 7 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 5 Mar 2025. 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 Sweden. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hildur Helgadottir, MD, PhD (+46(0)8 51773415, hildur.helgadottir@sll.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) in non-irradiated lesions (time frame: From date of precision radiation start until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 24 months). 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 5 Mar 2025; AzTrials last refreshed its copy on 8 Nov 2026.