NCT05341349

Stereotactic Radiosurgery and Immune Checkpoint Inhibitors With NovoTTF-200M for the Treatment of Melanoma Brain Metastases

Safety and Efficacy of SRS and Immune Checkpoint Inhibitors (ICI) Concurrent With NovoTTF-200M in Melanoma Brain Metastases

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 22 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial finds out the side effects and possible benefits of stereotactic radiosurgery and immune checkpoint inhibitors with NovoTTF-100M for the treating of melanoma that has spread to the brain (brain metastases). Stereotactic radiosurgery is a type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. It is used to treat brain tumors and other brain disorders that cannot be treated by regular surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. NovoTTF-100M is a portable battery operated device which produces tumor treating fields in the body by means of surface electrodes placed on the skin. Tumor treating fields are low intensity, intermediate frequency electric fields that pulse through the skin to disrupt cancer cells' ability to divide. Giving stereotactic radiosurgery and immune checkpoint inhibitors with NovoTTF-100M may work better than stereotactic radiosurgery and immune checkpoint inhibitors.

Detailed description

PRIMARY OBJECTIVE: I. To determine the safety of combining tumor treating fields therapy (TTFields) to the two therapeutic backbones (stereotactic radiosurgery \[SRS\]+pembrolizumab and SRS+dual-checkpoint). SECONDARY OBJECTIVES: I. To evaluate skin toxicity (grade 1 \& 2 skin \> 20% and grade 3 \& 4 toxicity above 2% at 4-6 weeks and 3 months). (Skin AES include Dermatitis, Erosions, Infections, Ulceration). II. Control of the treated lesion in the brain with SRS+ immune checkpoint inhibitors (ICI) (i.e. local control), development of additional sites of disease in the brain that were not initially treated with SRS (i.e. anywhere intra-cranial failure), intra-cranial progression free survival (local control of the area that received SRS and anywhere intra-cranial failure), extra-cranial disease response (overall progression free survival), and overall survival. III. To evaluate treatment response at un-irradiated and extra-cranial sites (i.e. the abscopal effect) with all three arms. IV. To compare differences in potential serological and immune biomarkers, pretreatment, during treatment, and post treatment. V. Symptomatic radionecrosis rates at 3 and 6 months. OUTLINE: Patients are assigned to 1 of 2 arms. ARM I: Patients receive standard of care pembrolizumab and undergo 3-5 fractions SRS. Patients also undergo TTFields over 8 hours daily using NovoTTF-100M device until intra-cranial progression or until end of immunotherapy treatments at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive standard of care nivolumab and ipilimumab and undergo 3-5 fractions SRS. Patients also undergo TTFields over 8 hours daily using NovoTTF-100M device until intra-cranial progression or until end of immunotherapy treatments at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 28 days.

Conditions

• Clinical Stage IV Cutaneous Melanoma AJCC v8
• Melanoma of Unknown Primary
• Metastatic Malignant Neoplasm in the Brain
• Metastatic Melanoma
• Metastatic Mucosal Melanoma
• Metastatic Ocular Melanoma
• Pathologic Stage IV Cutaneous Melanoma AJCC v8

Interventions

Type	Name	Description
BIOLOGICAL	Ipilimumab	Given IV
BIOLOGICAL	Nivolumab	Given IV
BIOLOGICAL	Pembrolizumab	Given IV
RADIATION	Stereotactic Radiosurgery	Undergo SRS
PROCEDURE	Tumor Treating Fields Therapy	Undergo TTFields

Timeline

• Start date: 2022-10-13
• Primary completion: 2026-03-06
• Completion: 2027-03-06
• First posted: 2022-04-22
• Last updated: 2025-07-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study