Precision Radiation of Immune Checkpoint Therapy Resistant Melanoma Metastases

  • End date
    Dec 19, 2025
  • participants needed
  • sponsor
    Karolinska University Hospital
Updated on 4 October 2022


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.


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 Simons 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 patients 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.

Condition Metastatic Melanoma, Stage IV Melanoma
Treatment Precision Radiation (SBRT)
Clinical Study IdentifierNCT04793737
SponsorKarolinska University Hospital
Last Modified on4 October 2022


Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

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
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note