Precision radiation for melanoma patients resistant to immune therapy

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial evaluates the effectiveness of precision radiation therapy (SBRT) in patients with metastatic melanoma who have shown progression while on PD-1 inhibitor treatment. The study is designed as a phase II open-label multicenter trial, focusing on the overall response rate in non-irradiated lesions after administering SBRT. Patients will continue their PD-1 inhibitor therapy for up to one year following radiation treatment, with follow-up assessments for 24 months or until disease progression or death. The trial employs a two-stage design to determine if the treatment is effective enough to warrant further patient recruitment.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Age 18 and above
2. ECOG performance status of 0-1
3. Signed and dated written informed consent before the start of specific protocol procedures.
4. 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.
5. Patients on adjuvant treatment with PD-1 inhibitors that during the treatment develop unresectable biopsy confirmed metastases can also be included in the study.
6. 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
7. No contraindication for continuing immunotherapy after the radiotherapy intervention

Exclusion Criteria:

1. Inability to understand given information or undergo study procedures according to protocol
2. Pregnant or breast-feeding. Patients must agree to use safe contraception during and for 3 months after study treatment.
3. 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.
4. Has an active infection requiring systemic therapy.
5. Concomitant therapy with any anti-tumor medications, other than PD-1/CTLA-4 inhibitors or 30 days before and after treatment in this trial.
6. Prior radiotherapy preventing the study intervention with precision radiotherapy
7. Location, size or number of metastases is deemed as excessive or not appropriate for precision radiotherapy
8. 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.
9. 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

Where it's running

• Division of Head-Neck, Lung and Skin cancers, Theme Cancer, Karolinska University Hospital
  Stockholm, Sweden Recruiting

Study contacts

• Study coordinator: Hildur Helgadottir, MD, PhD
• Email: hildur.helgadottir@sll.se
• Phone: +46(0)8 51773415

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.