Precision Radiation of Immune Checkpoint Therapy Resistant Melanoma Metastases

NCT04793737 | Recruiting

• 1 other identifier: PROMMEL
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Melanoma

Keywords

Precision radiation; PD-1 inhibitor; SBRT; Immune Checkpoint Inhibitor

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR) in non-irradiated lesions

  Overall response rate (ORR) in non-irradiated lesions according to RECIST 1.1

  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)

  6 and 12 months

• PFS rate (%)

  6 and 12 months

• Median OS (months)

  6 and 12 months

• Response rate (RR) in the patient's irradiated lesions

  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

  From precision radiation start to end of follow-up, progression or death, up to 24 months

Other Outcomes (1)

• Exploratory outcome measure: Predictive biomarkers

  From date of diagnosis until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 24 months

Study Arms (1)

Precision Radiation (SBRT)

EXPERIMENTAL

Precision radiation of melanoma metastases

Radiation: Precision Radiation (SBRT)

Interventions

Precision Radiation (SBRT) RADIATION

Precision radiation of melanoma metastases

Precision Radiation (SBRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Karolinska University Hospital: lead

Study Sites (1)

Division of Head-Neck, Lung and Skin cancers, Theme Cancer, Karolinska University Hospital

Stockholm, Sweden

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Signe Friesland, MD, PhD

  Karolinska University Hospital

  STUDY DIRECTOR

Central Study Contacts

Hildur Helgadottir, MD, PhD

CONTACT

+46(0)8 51773415; hildur.helgadottir@sll.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Phase II open-label multicenter trial

Study Record Dates

• First Submitted: February 17, 2021
• First Posted: March 11, 2021
• Study Start: March 8, 2021
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 5, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)