DaRT Seeds for Skin Cancer

Recruiting at 30 trial locations

Overseen By Aviya Hoida

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Academic

Sponsor: Alpha Tau Medical LTD.

Must not be taking: Immunosuppressants, Chemotherapy, Immunotherapy, others

Disqualifiers: Metastatic disease, T4 disease, others

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

Compensation: Varies

Number of Visits: 14

Duration: 2-3 weeks

86 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multi-center clinical study enrolling up to 86 participants. The primary objectives are to determine the objective response rate (ORR) established by the confirmed best overall response (BOR) following intratumoral administration of DaRT - Diffusing Alpha-Emitters Radiation Therapy, as well as to assess the Duration of Response (DOR) 6 months from initial response. Secondary objectives are to assess the safety of DaRT, and to assess the progression free survival (PFS), overall survival (OS), Overall Duration of Response (O-DOR), local control and quality of life (QOL) for patients treated with DaRT.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are undergoing systemic immunosuppressive therapy or have received certain treatments like chemotherapy, immunotherapy, or radiation therapy within 4 weeks of enrollment.

What data supports the effectiveness of the treatment DaRT224 for skin cancer?

Research shows that DaRT224, a treatment using alpha particles, effectively controls tumors in skin and head and neck cancers, with 100% response rates in some cases. It also enhances the body's immune response against tumors, making it a promising option for difficult-to-treat cancers. ^{1 2 3 4 5}

Is DaRT therapy safe for treating skin cancer?

DaRT therapy has been studied for safety in treating skin and head and neck cancers, showing it is feasible and generally safe. However, there is a potential risk to organs like the kidneys and red bone marrow due to radiation, but these risks are managed to stay within safe limits. ^{2 3 4 5 6}

How is the DaRT224 treatment different from other skin cancer treatments?

DaRT224 is unique because it uses alpha particles, which are a type of radiation, to target and kill cancer cells directly within the tumor. This treatment involves placing a small source of radiation inside the tumor, allowing the alpha particles to spread and create a high-dose area that can effectively destroy cancer cells, offering a new option for patients with limited treatment choices. ^{3 4 5 6 7}

Eligibility Criteria

This trial is for adults over 18 with recurrent skin cancer (cutaneous Squamous Cell Carcinoma) that's not treatable by surgery or standard radiation. Participants must have tried at least one standard treatment, be in fairly good health with a life expectancy of more than a year, and able to undergo CT scans. They should also agree to use effective birth control methods.

Inclusion Criteria

You are able to have a CT scan.

Platelets ≥100,000 mm3,

Measurable disease according to RECIST v 1.1.

Exclusion Criteria

My cancer has spread deeply or to nerves.

I have skin cancer that has not been treated and needs surgery or radiation.

My cancer is located in the mucosal, vulvar, anal, or penile areas.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

DaRT seeds are inserted into recurrent SCC tumors and removed after 14-21 days

2-3 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Multiple visits (in-person and virtual) over 12 months

Long-term follow-up

Assess overall survival, progression-free survival, and quality of life up to 12 months

12 months

Treatment Details

Interventions

• DaRT224

Trial Overview The study tests DaRT seeds - a type of internal radiation therapy - on up to 86 patients across multiple centers. It aims to see how well the treatment works (measured by tumor response), how long it lasts, its safety profile, and effects on survival rates and quality of life.

Participant Groups

Group I: DaRT seeds Experimental Treatment 1 Intervention

DaRT source will be inserted using preplanned radiotherapy parameters and reassessed by volumetric imaging 2-3 weeks after placement and then removed. Objective Response Rate (ORR) will be determined based on confirmed BOR following DaRT insertion.

Who Is Running the Clinical Trial?

Alpha Tau Medical LTD.

Lead Sponsor

Trials

28

Recruited

920+

Findings from Research

Diffusing alpha-emitters Radiation Therapy (DaRT) effectively enhances immune responses against tumors, showing improved tumor control when combined with anti-PD-1 therapy in mouse models of squamous cell carcinoma.

The combination of DaRT and anti-PD-1 therapy not only delayed tumor growth but also increased the infiltration of immune cells and altered the tumor microenvironment, suggesting a promising strategy for enhancing cancer treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diffusing Alpha-Emitters Radiation Therapy Promotes a Proimmunogenic Tumor Microenvironment and Synergizes With Programmed Cell Death Protein 1 Blockade. Mare, SD., Nishri, Y., Shai, A., et al.[2023]

Diffusing alpha-emitters radiation therapy (DART) uses radium-224 to treat solid tumors by releasing alpha-emitting atoms that create high-dose regions within the tumor, showing promising efficacy in preclinical studies on mice with squamous cell carcinoma and lung tumors.

Safety assessments indicate that DART can treat tumors weighing several hundred grams without exceeding tolerance doses in critical organs like the kidneys and red bone marrow, suggesting a favorable safety profile for this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of solid tumors by alpha emitters released from (224)Ra-loaded sources-internal dosimetry analysis. Arazi, L., Cooks, T., Schmidt, M., et al.[2013]

In a study involving 28 patients with locally advanced and recurrent squamous cancers, the novel alpha-emitter radiation therapy (DaRT) demonstrated a high complete response rate of 78.6% for treated lesions, indicating its efficacy in tumor reduction.

The treatment was associated with manageable acute toxicities, primarily local pain and mild skin ulceration, with no severe grade 3 or higher toxicities reported, suggesting a favorable safety profile for this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Safety and Tumor Control Results From a "First-in-Human" Multicenter Prospective Trial Evaluating a Novel Alpha-Emitting Radionuclide for the Treatment of Locally Advanced Recurrent Squamous Cell Carcinomas of the Skin and Head and Neck. Popovtzer, A., Rosenfeld, E., Mizrachi, A., et al.[2020]

The study evaluated the use of diffusing alpha-emitter radiation therapy (DaRT) in 10 patients with recurrent or unresectable skin cancers, showing a 100% complete response rate at 12 weeks post-treatment, with 90% of these responses confirmed by CT imaging.

DaRT demonstrated a favorable safety profile, with no severe device-related adverse events reported, and only mild to moderate side effects like erythema and edema, indicating it may be a promising treatment option for patients with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Safety of Diffusing Alpha-Emitter Radiation Therapy for Recurrent or Unresectable Skin Cancers. D'Andrea, MA., VanderWalde, NA., Ballo, MT., et al.[2023]

Diffusing alpha-emitters radiation therapy (DART) significantly inhibited tumor growth in lung carcinoma models, with a 93% reduction in tumor development for the A427 model and a 49% reduction for the LL2 model, leading to a 48% increase in life expectancy for LL2 tumors.

In human-derived tumor models, over 80% of treated tumors either shrank or disappeared, demonstrating the potential efficacy of DART in treating solid tumors, supported by histological evidence of tumor necrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local control of lung derived tumors by diffusing alpha-emitting atoms released from intratumoral wires loaded with radium-224. Cooks, T., Schmidt, M., Bittan, H., et al.[2013]

Alpha DaRT, a new radiation therapy using alpha particles, can significantly reduce tumor cell survival by up to 200 times due to the low-LET dose from beta emissions, while sparing surrounding healthy tissue.

The study shows that increasing the source activity of 224Ra can enhance the therapeutic effect of Alpha DaRT, potentially allowing for greater spacing between sources while maintaining efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The low-LET radiation contribution to the tumor dose in diffusing alpha-emitters radiation therapy. Epstein, L., Heger, G., Roy, A., et al.[2023]

The study developed a two-dimensional finite element model to estimate the dose delivered by Diffusing alpha-emitters Radiation Therapy (DaRT), showing that it closely matches previous numerical methods (DART1D and DART2D) with less than 1% difference in the source midplane over a 30-day treatment period.

The findings indicate that the dose can vary significantly (by over a factor of 3) at a distance of 2 mm from the source, highlighting the need for further research to refine the parameters of the Diffusion-Leakage model for more accurate treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A finite element method for modeling diffusion of alpha-emitting particles in tissue. Zhang, IP., Cohen, GN., Damato, AL.[2023]

References

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

Diffusing Alpha-Emitters Radiation Therapy Promotes a Proimmunogenic Tumor Microenvironment and Synergizes With Programmed Cell Death Protein 1 Blockade. [2023]

2. England pubmed.ncbi.nlm.nih.gov

The treatment of solid tumors by alpha emitters released from (224)Ra-loaded sources-internal dosimetry analysis. [2013]

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

Initial Safety and Tumor Control Results From a "First-in-Human" Multicenter Prospective Trial Evaluating a Novel Alpha-Emitting Radionuclide for the Treatment of Locally Advanced Recurrent Squamous Cell Carcinomas of the Skin and Head and Neck. [2020]

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

Feasibility and Safety of Diffusing Alpha-Emitter Radiation Therapy for Recurrent or Unresectable Skin Cancers. [2023]

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

Local control of lung derived tumors by diffusing alpha-emitting atoms released from intratumoral wires loaded with radium-224. [2013]

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

The low-LET radiation contribution to the tumor dose in diffusing alpha-emitters radiation therapy. [2023]

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

A finite element method for modeling diffusion of alpha-emitting particles in tissue. [2023]