Intratumoral Targeted Hyperthermia Therapy (THT) for Cutaneous Metastatic Melanoma

Intra-tumoral Targeted Hyperthermic Therapy (THT) for Stage 3C/3D/4M1 Cutaneous Metastatic Melanoma in Patients With Targetable Cutaneous and/or Sub-cutaneous Tumors

This device phase I/II, first in human, early feasibility study (EFS), open-label, single-arm trial aims to evaluate the safety, tolerability, and preliminary efficacy of Gold Nanorod (GNR)-enabled sub-ablative targeted hyperthermia therapy (THT) in patients with unresectable stage 3C/3D/4M1 cutaneous metastatic malignant melanoma that have failed to respond to systemic checkpoint and localized intra-tumoral immunotherapy. The study will involve up to 10 participants with stable or progressive cutaneous and/or subcutaneous skin lesions (Immune Stable Disease (iSD) or Immune Confirmed/Unconfirmed Progressive Disease (iCPD/iUPD)).

GNRs, when administered via intra-tumoral injection and activated by NIR light, generate localized heat through a process called THT. This approach selectively targets tumor cells while minimizing damage to surrounding healthy tissue. In this study, 10 participants will receive two THT treatments spaced 7 days apart.

The primary objective of this study is to assess the safety and tolerability of THT treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Cutaneous Metastatic Melanoma
• Intervention / Treatment: Device: Targeted Hyperthermia Therapy

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carman Giacomantonio, MD; Phone Number: 902-473-6177; Email: carman.giacomantonio@nshealth.ca
• Study Contact Backup: Name: Len Pagliaro, PhD; Phone Number: +1 (425) 443-4344; Email: len@sonanano.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 16 years of age or older;
2. Participants with histologically or cytologically confirmed stage 3C/3D/4M1 advanced or cutaneous metastatic melanoma, with measurable disease by iRECIST 1.1 criteria, including any number of cutaneous lesions;
3. Present a visible and accessible primary tumor or metastatic deposit (any site) that has not been surgically removed;
4. Present target tumors of ≤2.5 cm in diameter;
5. Participants must have received and failed systemic and local intra-tumoral therapy at least one prior standard therapy, including immune checkpoint inhibitors (e.g., anti- PD1 or anti-CTLA-4), and failed local intra-tumoral IL-2 treatment. Failed response to treatment will be categorized according to iRECIST guidelines. Patients who have: a) Immune partial response (iPR): At least a 30% decrease in the sum of diameters of target lesions compared to baseline, no progression of non-target lesions, No new lesions; or b) Immune Stable Disease (iSD): Neither sufficient reduction to qualify for iPR nor sufficient increase to qualify for iCPD (immune confirmed progressive disease), no new lesions; or c) Immune Unconfirmed Progressive Disease (iUPD): At least a 20% increase in the sum of diameters of target lesions, taking the smallest sum on study as the reference, appearance of new lesions, iUPD needs confirmation after at least 4 weeks; if confirmed, it becomes iCPD; or d) Immune Confirmed Progressive Disease (iCPD): iUPD must be confirmed in a follow-up assessment (minimum of 4 weeks after initial iUPD), if progressive disease (increase in lesion size or additional new lesions) is still evident upon re-evaluation, iCPD is confirmed.
6. Participants must agree to discontinue treatment with local intralesional immunotherapies during the study, with resumption after completion of the trial;
7. ECOG Performance Status: ≤1;
8. Life expectancy: ≥6 months;
9. Participants able and willing to provide written informed consent and comply with the trial protocol.
10. Either BRAF positive (BRAF+) or BRAF negative (BRAF-).

Exclusion criteria:

1. Women who are pregnant, breastfeeding, or planning to become pregnant during the study. Women of childbearing potential must have a negative pregnancy test within 72 hours prior to enrollment and agree to use adequate contraception throughout the study;
2. Any infection requiring systemic therapy or other concurrent medical conditions (e.g., hepatitis B, hepatitis C, HIV) that would interfere with the study;
3. Myocardial infarction or stroke within the past 6 months, uncontrolled angina, or significant arrhythmia;
4. Participants receiving blood thinners as part of therapeutic anticoagulation therapy;
5. Any severe or uncontrolled comorbid condition that, in the investigator's opinion, would pose excessive risk to the participants (e.g., immunodeficiencies, severe hypertension, uncontrolled diabetes, liver failure);
6. Participation in another clinical trial involving an investigational product/device within 30 days prior to screening;
7. Any condition that would impede compliance with study procedures;
8. Participants with a known allergy to gold of any kind;
9. Participants who are unable to tolerate cutaneous injections for any reason will not be eligible;
10. Participants with a known allergy to injectable local analgesics;
11. Participants with ocular melanoma or melanoma involving periorbital skin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• 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: Targeted Hyperthermia Therapy	Device: Targeted Hyperthermia Therapy; Intra-tumoral gold nanorods (SivaRods) exposed to Near Infrared Light (860 +/- 10nm) mediated targeted hyperthermia therapy; Other Names: Gold Nanorods; Gold Nanoparticles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants that successfully complete THT (maintain intra-tumoral temperatures of 42-48C)	Total number of participants that successfully complete targeted hyperthermia therapy ie. maintain an intra-tumoral temperatures between 42-48C for 5 minutes	1 year
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	The total number of participants experiencing adverse events, including serious adverse events, will be monitored and graded according to NCI CTCAE v5.0	1 year
Number of participants that have a tumor response as assessed by iRECIST 1.1 criteria	The total number of participants that have a tumor response to targeted hyperthermia therapy as assessed by iRECIST 1.1 criteria	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participant's that have an increase in immune cell infiltrates in the tumor biopsy and blood samples post THT compared to pre-treatment patient samples	The total number of participants that have an increase in immune cell infiltrates in their tumor biopsy and blood samples following targeted hyperthermia therapy compared to patients biopsy and blood samples obtained before treatment	1 year

Collaborators and Investigators

• Sponsor: Sona Nanotech Inc
• Collaborators: Nova Scotia Health Authority
• Investigators: Principal Investigator: Lucy K Helyer, MD, Nova Scotia Health

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: February 21, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 11, 2025

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Hyperthermia; Near Infrared Light; Gold Nanorods; Targeted Hyperthermia; Cutaneous Metastatic Melanoma Treatment
• Additional Relevant MeSH Terms: Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hyperthermia
• Other Study ID Numbers: 69231

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No