Focused Ultrasound and PolyICLC for Melanoma

(Mel 70 Trial)

Overseen By Olena Glushakova

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Virginia

Must be taking: Checkpoint blockade

Must not be taking: Radiation, Corticosteroids, Chemotherapy, others

Disqualifiers: Addiction, HIV, Hepatitis, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 3 weeks

11 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for advanced melanoma, a serious skin cancer. The treatment combines focused ultrasound, which uses sound waves to heat and destroy cancer cells, with polyICLC (polyinosinic-polycytidylic acid stabilized with carboxymethylcellulose and polylysine), a drug that activates the immune system. Participants should currently receive immunotherapy and plan to have surgery for their melanoma. This trial may suit those whose cancer is visible on an ultrasound and who are already undergoing checkpoint blockade therapy. Neither the ultrasound method nor the polyICLC drug has FDA approval, making this an experimental study. As an Early Phase 1 trial, the study aims to understand how the new treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications. However, you cannot take certain treatments within 4 weeks of starting the trial, such as radiation therapy, high doses of systemic corticosteroids, growth factors, interleukins, investigational agents, targeted therapies for BRAF or MEK mutations, live vaccines, interferon, and cytotoxic chemotherapy. If you are on any of these, you may need to stop them before joining the trial.

What prior data suggests that this device and drug combination is safe for treating melanoma?

Research has shown that focused ultrasound ablation (FUSA) and polyICLC remain experimental treatments, with limited solid information about their safety in humans. The researchers aim to determine if these treatments are safe and manageable for individuals with advanced melanoma.

FUSA is a non-invasive technique that uses sound waves to heat and destroy tumor tissue, targeting specific areas to potentially protect nearby healthy tissue. PolyICLC is a drug designed to enhance the immune system's ability to fight cancer.

As this is an early-stage study, previous trials provide limited safety information. In this early phase, the primary focus is to assess safety and treatment tolerance in a small group. Participants will receive close monitoring for any side effects or adverse reactions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for melanoma, which often include surgery, chemotherapy, or immunotherapy, the combination of Focused Ultrasound Ablation (FUSA) and polyICLC offers a unique approach. This treatment uses focused ultrasound to precisely target and destroy tumor cells, while polyICLC, an immune system stimulant, is injected directly into the tumor to enhance the body's immune response. Researchers are excited about this approach because it not only targets the tumor directly but also potentially boosts the immune system to recognize and fight cancer cells more effectively, potentially leading to improved outcomes with fewer side effects.

What evidence suggests that this trial's treatments could be effective for melanoma?

Studies have shown that focused ultrasound ablation (FUSA) effectively targets and destroys tumor tissue using sound waves. This non-invasive method has been explored in treating various cancers. Research indicates that PolyICLC, an experimental drug, helps the immune system better recognize and fight cancer cells. In this trial, participants will receive a combination of FUSA and PolyICLC. Although the FDA has not approved either FUSA or PolyICLC, early evidence suggests that using them together could boost the body's immune response against melanoma. The treatment remains experimental but shows promise by enhancing immune activity and targeting tumors. ^{1 2 6 7 8}

Who Is on the Research Team?

Lynn Dengel, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for adults with advanced melanoma who are undergoing immunotherapy and planning surgery. Participants must meet certain health criteria to be eligible, but specific inclusion and exclusion details aren't provided here.

Inclusion Criteria

I have advanced melanoma and am scheduled for surgery.

I am currently on checkpoint inhibitor therapy.

My biopsy can be done with or without imaging.

Exclusion Criteria

I haven't had polyICLC treatment in the last 4 weeks without severe side effects.

I have had cancer before, but it's one of the exceptions.

I have severe heart disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive focused ultrasound ablation (FUSA) and an intratumoral injection of polyICLC

3 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• FUSA
• PolyICLC

Trial Overview The study tests focused ultrasound ablation (FUSA), a non-invasive method using ultrasound waves to destroy tumor tissue, combined with an immune-activating injection called polyICLC in patients before surgery.

How Is the Trial Designed?

Group I: FUSA + polyICLC Experimental Treatment 2 Interventions

Focused Ultrasound Ablation plus intratumoral injection of polyICLC

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Theraclion

Industry Sponsor

Trials

22

Recruited

730+

Published Research Related to This Trial

The study developed an innovative drug delivery system using ultrasound to target and release doxorubicin, a chemotherapy drug, specifically at desired locations, showing promising encapsulation efficiency of 20.5% and a maximum drug load of 6.2 mg Dox/g PLA.

In vitro and in vivo tests demonstrated that the ultrasound contrast agent provided significant acoustic enhancement, with a peak size of 1865 nm and a half-life of over 15 minutes, indicating its potential effectiveness for targeted cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and optimization of a doxorubicin loaded poly(lactic acid) contrast agent for ultrasound directed drug delivery. Eisenbrey, JR., Burstein, OM., Kambhampati, R., et al.[2021]

Using focused ultrasound (FUS) to deliver hyaluronic acid (HA) conjugates of camptothecin (CPT) and doxorubicin (DOX) significantly improves drug penetration into the brain in a mouse model of glioblastoma multiforme (GBM).

The study found that the ratio of DOX to CPT in the conjugates affects their flexibility, which in turn influences the effectiveness of the treatment, with more flexible conjugates showing better efficacy against GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-mediated delivery of flexibility-tunable polymer drug conjugates for treating glioblastoma. Sun, T., Krishnan, V., Pan, DC., et al.[2023]

Combining ultrasound (US) with doxorubicin (DOX)-loaded PLGA microspheres significantly enhances tumor cell killing in melanoma models, demonstrating a synergistic effect that improves treatment efficacy.

In melanoma-bearing mice, this combination therapy extended mean survival to 22.1 days compared to 10.4 days for untreated mice, indicating its potential as a promising alternative treatment for otherwise incurable cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining ultrasound and intratumoral administration of doxorubicin-loaded microspheres to enhance tumor cell killing. Do, AV., Geary, SM., Seol, D., et al.[2021]

The study developed melanin-cored, doxorubicin-loaded nanodroplets that effectively penetrate solid tumors and enhance drug delivery using a novel opto-acoustic synergistic irradiation (OASI) method, demonstrating good biocompatibility.

In vivo experiments showed that this approach not only improved the accumulation of doxorubicin in tumors but also effectively eliminated melanoma tumors through a combination of mechanical disruption and subsequent laser irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opto-acoustic synergistic irradiation for vaporization of natural melanin-cored nanodroplets at safe energy levels and efficient sono-chemo-photothermal cancer therapy. Hu, Y., Xue, S., Long, T., et al.[2021]

The study found that DNA complexes made with reducible polycations can enhance gene delivery effectiveness while maintaining a longer circulation time in the bloodstream compared to non-reducible polycations.

These polyplexes can be targeted both molecularly, using specific protein ligands, and physically, through ultrasound, suggesting they could be a promising method for delivering cancer gene therapies directly to tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-enhanced transfection activity of HPMA-stabilized DNA polyplexes with prolonged plasma circulation. Zhou, QH., Miller, DL., Carlisle, RC., et al.[2016]

In a study involving 16 patients with metastatic malignant melanoma, treatment with poly(I,C)-LC did not result in any antitumor responses, indicating limited efficacy for this intervention.

The treatment caused significant side effects, including high fevers (over 40 degrees C) and fatigue, which were dose-limiting, with one patient experiencing a fever of 42.2 degrees C after consecutive doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Eastern Cooperative Oncology Group phase I-II pilot study of polyriboinosinic-polyribocytidylic acid poly-L-lysine complex in patients with metastatic malignant melanoma. Hawkins, MJ., Levin, M., Borden, EC.[2020]

The study introduces a new treatment method using a nanoscale coordination polymer (pIC@NCP) that selectively delivers immune modulators to tumors, enhancing the effectiveness of immune checkpoint blockade (ICB) therapies.

In mouse models of colorectal and prostate cancer, pIC@NCP demonstrated significant tumor growth inhibition by activating the immune response, suggesting it could improve outcomes for patients with immunogenic tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TLR3 agonist nanoscale coordination polymer synergizes with immune checkpoint blockade for immunotherapy of cancer. Li, Y., Jiang, X., Luo, T., et al.[2023]

The PSPEI-PAA nanocomplexes, developed for delivering tumor lysate protein and poly I:C, showed significant effectiveness in suppressing tumor growth in a murine melanoma model without noticeable toxicity, indicating a promising treatment strategy.

These nanocomplexes enhanced the maturation of dendritic cells and increased the infiltration of CD8+ T cells into tumors, suggesting they could effectively boost the immune response against malignant melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-Assembled, Adjuvant/Antigen-Based Nanovaccine Mediates Anti-Tumor Immune Response against Melanoma Tumor. Rajendrakumar, SK., Mohapatra, A., Singh, B., et al.[2020]

Pulsed high-intensity focused ultrasound significantly enhances the delivery of liposomal doxorubicin to tumors, with a 124% increase in drug concentration compared to untreated tumors, as shown in a study involving 32 mice.

The mechanism behind this enhanced delivery involves increased extravasation of drugs into tumor tissue, which was confirmed through in vivo confocal microscopy observations of treated tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery of systemic chemotherapeutic agent to tumors by using focused ultrasound: study in a murine model. Yuh, EL., Shulman, SG., Mehta, SA., et al.[2013]

The study developed a novel type of thermosensitive liposome (PTSL) that is sensitive to both temperature and pH, which showed enhanced cytotoxicity and required lower thermal doses when combined with MR-guided focused ultrasound (MRgFUS) in vitro.

In vivo experiments demonstrated that the MRgFUS/PTSL delivery platform significantly reduced tumor burden more effectively than traditional drug formulations, leading to better tumor penetration and cell destruction, indicating a promising strategy for localized chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Localized delivery of doxorubicin in vivo from polymer-modified thermosensitive liposomes with MR-guided focused ultrasound-mediated heating. Ta, T., Bartolak-Suki, E., Park, EJ., et al.[2021]

Fluorocarbon modified chitosan (FCS) combined with the immune adjuvant poly(I:C) forms nanoparticles that can be delivered transdermally, effectively activating immune cells and inducing tumor repression in melanoma.

This transdermal delivery method significantly enhances the efficacy of PD-1 blockade therapy, suggesting a promising new approach to improve immunotherapy outcomes in melanoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorocarbon Modified Chitosan to Enable Transdermal Immunotherapy for Melanoma Treatment. Zhuang, Q., Chao, T., Wu, Y., et al.[2023]

A new nano-sized ultrasound contrast agent (UCA) made from polylactic acid was developed, which can enhance tumor imaging by passing through the leaky blood vessels of tumors more effectively than larger agents.

The study found that the viscosity of the colloidal suspension used to create the UCA significantly affects its size and echogenicity, with a balance needed between size, imaging quality, and stability for optimal performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nano-sized ultrasound contrast agent: salting-out method. Wheatley, MA., Lewandowski, J.[2020]

In a pilot study involving patients with recurrent metastatic head and neck squamous cell cancer and melanoma, poly-ICLC was well tolerated and showed promising immune responses, with one patient achieving stable disease for 6 months after treatment.

The treatment led to significant changes in immune markers, such as increased levels of CD4, CD8, PD1, and PD-L1 in the tumor of the patient who benefited, indicating that poly-ICLC may effectively activate the immune system against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Immune Modulation against Solid Cancers with Intratumoral Poly-ICLC: A Pilot Trial. Kyi, C., Roudko, V., Sabado, R., et al.[2022]

The study developed echogenic heat-sensitive liposomes (E-LTSL) that enhance the half-life of ultrasound contrast agents, allowing for better monitoring of drug delivery and tumor temperature in real-time during cancer treatment.

Using motion compensation techniques, the researchers achieved a significant reduction in image intensity variation, which improved the accuracy of measuring temperature changes in tumors and correlated with enhanced delivery of the chemotherapy drug doxorubicin (Dox) at elevated temperatures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motion Compensated Ultrasound Imaging Allows Thermometry and Image Guided Drug Delivery Monitoring from Echogenic Liposomes. Ektate, K., Kapoor, A., Maples, D., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06472661

NCT06472661 | FUSA With Intratumoral PolyICLC in ... This study is for adult patients with advanced melanoma who are receiving immunotherapy and who are planning on having surgery for their cancer.

2. withpower.com withpower.com/trial/early-phase-1-melanoma-7-2024-874e4

Focused Ultrasound and PolyICLC for Melanoma (Mel 70 Trial) This study is for adult patients with advanced melanoma who are receiving immunotherapy and who are planning on having surgery for their cancer.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06472661?term=AREA%5BConditionSearch%5D(Advanced%20Melanoma)%20AND%20AREA%5BBasicSearch%5D(Recruiting)%20AND%20AREA%5BOverallStatus%5D(RECRUITING)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=2

FUSA With Intratumoral PolyICLC in Regionally Advanced ... This study is for adult patients with advanced melanoma who are receiving immunotherapy and who are planning on having surgery for their cancer.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3095464/

High intensity focused ultrasound in clinical tumor ablation This paper reviews the clinical outcomes of HIFU ablation for applicable cancers, and then summarizes the recommendations for a satisfactory HIFU treatment ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/condition/25017/melanoma

Melanoma Clinical Research Trials The aim of this study is to evaluate the effectiveness of the Digizorg Melanoma SCP app in terms of patient and provider-reported outcomes and clinical practice ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-08789

Focused Ultrasound Ablation and Intratumoral PolyICLC ... Giving FUSA and intratumoral polyICLC may be safe, tolerable and/or effective in treating patients with advanced resectable melanoma receiving immunotherapy ...

7. trials.braintumor.org trials.braintumor.org/?_ga=2.68950737.1939810904.1742313252-1235739541.1677157867&_gac=1.82299620.1742476825.Cj0KCQjw-e6-BhDmARIsAOxxlxUp0zP369iGSp-SfXUSUaOxU_lpTbpdD27414VUDmOwtyF1DwisZG8aAoFlEALw_wcB&_gl=1%2A1phw64c%2A_gcl_aw%2AR0NMLjE3NDI0NzY4MjUuQ2owS0NRanctZTYtQmhEbUFSSXNBT3h4bHhVcDB6UDM2OWlHU3AtU2ZYVVNVYU94VV9scFRicGREMjc0MTRWVURtT3d0eUYxRHdpc1pHOGFBb0ZsRUFMd193Y0I.%2A_ga%2AMTIzNTczOTU0MS4xNjc3MTU3ODY3%2A_ga_SX7BRZW1WF%2AMTc0MjQ3NjQ2NS40MzguMS4xNzQyNDc2ODI1LjYwLjAuMA..&page=88

Filters - Clinical Trial Finder - National Brain Tumor Society All participants in this study will receive an experimental treatment made up of focused ultrasound ablation (FUSA), a non-invasive experimental treatment that ...

8. stage.webhealthnetwork.com stage.webhealthnetwork.com/clinicaltrials-details.php?id=10174

Clinical Trial - Abdominal Tumors - WebHealth Network The principle of HIFU is physically focus the ultrasound point on the biological tissue to form high-intensity ultrasound focus, and kill tumor cells by the ...