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

Trial Summary

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 data supports the idea that Focused Ultrasound and PolyICLC for Melanoma is an effective treatment?

The available research does not directly provide data on the effectiveness of Focused Ultrasound and PolyICLC for Melanoma. However, it does show that similar treatments using focused ultrasound combined with other drugs, like doxorubicin, can significantly extend survival in melanoma models. For example, in one study, mice treated with ultrasound and doxorubicin-loaded microspheres lived longer than those receiving other treatments. This suggests that focused ultrasound can enhance the effectiveness of certain cancer treatments, which might imply potential for Focused Ultrasound and PolyICLC as well. ^{1 2 3 4 5}

What safety data exists for Focused Ultrasound and PolyICLC treatment for melanoma?

The safety data for PolyICLC, a component of the treatment, indicates it is generally well tolerated. In a pilot trial, PolyICLC was administered intratumorally and intramuscularly to patients with solid cancers, including melanoma. The main side effects were fatigue and injection site inflammation, both less than grade 2 in severity. Another study involving intravenous administration of PolyICLC in melanoma patients reported fever and fatigue as dose-limiting toxicities. No antitumor responses were observed in this study. Overall, PolyICLC has shown to be safe with manageable side effects, warranting further investigation in clinical trials. ^{6 7 8 9 10}

Is the treatment PolyICLC a promising treatment for melanoma?

The information provided does not directly address the effectiveness of PolyICLC for melanoma. The articles focus on ultrasound and other drug delivery methods, but do not mention PolyICLC specifically. Therefore, based on the given information, we cannot determine if PolyICLC is a promising treatment for melanoma. ^{1 11 12 13 14}

What is the purpose of this trial?

This study is for adult patients with advanced melanoma who are receiving immunotherapy and who are planning on having surgery for their cancer. All participants in this study will receive an experimental treatment made up of focused ultrasound ablation (FUSA), a non-invasive experimental treatment that uses ultrasound waves to heat and destroy tumor tissue, and an injection in the tumor with an experimental drug that activates the immune system called polyICLC (polyinosinic-polycytidylic acid that is stabilized with carboxymethylcellulose and polylysine). Neither the drug nor the device that are used in this study have been approved by the U.S. Food and Drug Administration (FDA).

Research Team

Lynn Dengel, MD

Principal Investigator

University of Virginia

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

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]

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 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]

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]

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]

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 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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Combining ultrasound and intratumoral administration of doxorubicin-loaded microspheres to enhance tumor cell killing. [2021]

2. Australia 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. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Localized delivery of doxorubicin in vivo from polymer-modified thermosensitive liposomes with MR-guided focused ultrasound-mediated heating. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Ultrasound-mediated delivery of flexibility-tunable polymer drug conjugates for treating glioblastoma. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Ultrasound-enhanced transfection activity of HPMA-stabilized DNA polyplexes with prolonged plasma circulation. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Therapeutic Immune Modulation against Solid Cancers with Intratumoral Poly-ICLC: A Pilot Trial. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Fluorocarbon Modified Chitosan to Enable Transdermal Immunotherapy for Melanoma Treatment. [2023]

8. United States 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. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Self-Assembled, Adjuvant/Antigen-Based Nanovaccine Mediates Anti-Tumor Immune Response against Melanoma Tumor. [2020]

10. Netherlands pubmed.ncbi.nlm.nih.gov

TLR3 agonist nanoscale coordination polymer synergizes with immune checkpoint blockade for immunotherapy of cancer. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Nano-sized ultrasound contrast agent: salting-out method. [2020]

12. United States pubmed.ncbi.nlm.nih.gov

Delivery of systemic chemotherapeutic agent to tumors by using focused ultrasound: study in a murine model. [2013]

13. Australia pubmed.ncbi.nlm.nih.gov

Motion Compensated Ultrasound Imaging Allows Thermometry and Image Guided Drug Delivery Monitoring from Echogenic Liposomes. [2018]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Development and optimization of a doxorubicin loaded poly(lactic acid) contrast agent for ultrasound directed drug delivery. [2021]