Single Arm Trial of Tumor-Treating Fields in Combination With Nivolumab and Ipilimumab in Metastatic Uveal Melanoma

Tumor Treating Fields targeted to liver metastases may improve outcomes for patients with metastatic uveal melanoma treated with immune checkpoint inhibitors.

Study Overview

• Status: Completed
• Conditions: Uveal Melanoma
• Intervention / Treatment: Device: Novocure Optune; Drug: Opdivo; Drug: Yervoy

Detailed Description

Uveal melanoma is the most common ocular malignancy for adults and despite effective therapies, roughly 50% of patients will develop metastatic disease. Currently there is no therapy to improve the prognosis of patients with metastatic disease and these patients are usually treated with regimens used for cutaneous melanoma. Tumor Treating Fields is a new type of anti-cancer therapy approved by the FDA for use in glioblastoma multiforme and mesothelioma. TTF has been shown to activate the STING pathway leading to increased levels of dendritic cells in regional lymph nodes.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Insititute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient has histologically or cytologically confirmed metastatic uveal melanoma with predominant liver involvement
2. Age 18 years or older and willing and able to provide informed consent
3. WOCBP must have a negative serum pregnancy test documented with 72 hours of first administration of drug
4. Sexually active and WOCBP, patient and partner must agree to use adequate contraception
5. Normal organ and marrow function
6. ECOG 0-1
7. Life expectancy of 3 months or greater

Exclusion Criteria:

1. History of previous grade 3, life threatening immune related adverse event (irAE) from prior checkpoint inhibitor therapy
2. Prior treatment with anti cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4) therapy within 90 days of C1D1 of study treatment
3. Prior anti-cancer therapy (systemic, regional or radiation) within 2 weeks of C1D1 of study treatment
4. AEs from prior anticancer therapies that have not resolved to grade 1 or less, other than endocrine related irAEs for which patients are on appropriate replacement therapy (ie hypothyroidism, adrenal insufficiency, type 1 diabetes)
5. History of or active autoimmune disease requiring systemic corticosteroid or immunosuppressive therapy. (Patients who have limited autoimmune disease not requiring systemic therapy or autoimmune disease that is unlikely to recur, such as ulcerative colitis s/p colectomy, will be allowed to enroll.)
6. Serious medical risk factors involving any of the major organ systems such that the Investigator considers it unsafe for the patient to receive an experimental research drug.
7. Patient is unwilling or unable to comply with study procedures
8. Patients with implanted pacemaker, defibrillator, nerve stimulator or other active electronic medical devices; sensitive to conductive hydrogels used on electrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes typically used for TTFields studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TTF Plus Chemotherapy; Novacure Optune with Opdivo and Yervoy	Device: Novocure Optune; Novacure Optune with Opdivo and Yervoy; Drug: Opdivo; Novacure Optune with Opdivo and Yervoy; Other Names: Nivolumab; Drug: Yervoy; Novacure Optune with Opdivo and Yervoy; Other Names: Ipilimumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	evaluate the overall response rate of patients with mUM treated with TTF in combination with nivolumab and ipilimumab.	from the initiation of study treatment and through study completion, up to 1 year
Overall Safety	Evaluate the safety of TTF in combination with nivolumab and ipilimumab (Number of patients who developed grade 3 treatment-related adverse events as assessed by CTCAE v5)	From the initiation of study treatment and through study completion, up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival Rate	to assess the median progression free survival and overall survival of treated patients.	From initiation of study treatment until date of death from any cause, up to 100 months

Collaborators and Investigators

• Sponsor: HonorHealth Research Institute
• Collaborators: NovoCure Ltd.
• Investigators: Principal Investigator: Justin Moser, MD, HonorHealth Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2022
• Primary Completion (Actual): November 18, 2024
• Study Completion (Actual): July 23, 2025

Study Registration Dates

• First Submitted: June 16, 2021
• First Submitted That Met QC Criteria: August 5, 2021
• First Posted (Actual): August 13, 2021

Study Record Updates

• Last Update Posted (Estimated): August 15, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Eye Diseases; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Eye Neoplasms; Uveal Diseases; Melanoma; Uveal Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Nivolumab; Ipilimumab
• Other Study ID Numbers: TTFields-UM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes