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

Phase 1

Recruiting

• Conditions: Uveal Melanoma
• Interventions: Device: Novocure Optune; Drug: Opdivo; Drug: Yervoy

• Registration Number: NCT05004025
• Lead Sponsor: HonorHealth Research Institute

Brief Summary

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

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 Timeline

• Study First Submitted: 2021-06-16
• Study First Submitted QC: 2021-08-05
• Study First Posted: 2021-08-13
• Study Start: 2022-02-28
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-14
• Last Update Posted: 2024-06-17
• Primary Completion: 2025-08
• Study Completion: 2025-08-29

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TTF Plus Chemotherapy	Novocure Optune	Novacure Optune with Opdivo and Yervoy
TTF Plus Chemotherapy	Opdivo	Novacure Optune with Opdivo and Yervoy
TTF Plus Chemotherapy	Yervoy	Novacure Optune with Opdivo and Yervoy

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	from the initiation of study treatment and through study completion, up to 1 year	evaluate the overall response rate of patients with mUM treated with TTF in combination with nivolumab and ipilimumab.
Overall Safety	From the initiation of study treatment and through study completion, up to 1 year	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)

Secondary Outcome Measures

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

Trial Locations

Locations (2)

The Angeles Clinic and Research Insititute; 🇺🇸 Los Angeles, California, United States

HonorHealth Research Institute; 🇺🇸 Scottsdale, Arizona, United States