DaRT Seeds for Skin Cancer

Recruiting at 32 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called DaRT (Diffusing Alpha-Emitters Radiation Therapy), which uses tiny radioactive seeds to treat skin cancer, specifically when it returns after other treatments fail. The main goal is to assess how well DaRT shrinks tumors and prevents them from returning over time. The trial also evaluates DaRT's safety and its impact on patients' quality of life. Individuals with a single skin cancer tumor that cannot be removed by surgery or standard radiation, and that has returned after other treatments failed, might be suitable for this trial. As an unphased trial, it offers patients a unique opportunity to explore a novel treatment option that could potentially enhance their quality of life.

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 prior data suggests that DaRT is safe for treating skin cancer?

Previous studies have shown promising safety results for DaRT224. Research indicates that this treatment, which delivers radiation directly to tumors, is well-tolerated by patients with skin cancer. One study suggested that DaRT224 has fewer side effects compared to traditional radiation therapies. Another study supported its good safety record, showing that it can be safe for treating challenging skin cancers.

Overall, DaRT224 appears to be a safe option for patients, with few reported side effects. As further trials study it, more information will help confirm these findings. For now, the data looks encouraging for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for skin cancer, which often include surgical removal, chemotherapy, or topical medications, DaRT224 is unique because it uses a novel delivery method involving DaRT seeds. These seeds are implanted directly into the tumor, delivering targeted radiation precisely where it's needed. This approach minimizes damage to surrounding healthy tissue and aims to improve the Objective Response Rate (ORR) by reassessing the tumor size with imaging before removing the seeds. Researchers are excited about DaRT224 because it could offer a more precise and less invasive treatment option for skin cancer patients.

What evidence suggests that DaRT224 is effective for skin cancer?

Research has shown that DaRT224, a type of radiation therapy, may effectively treat skin cancer. In one study, 79% of skin cancer spots treated with DaRT completely disappeared. Another study found a high success rate in treating squamous cell carcinoma with only minor side effects. Patients generally tolerated the treatment well, with few negative effects reported. These results suggest that DaRT224 could be a promising option for skin cancer treatment. Participants in this trial will receive DaRT224 to further evaluate its effectiveness and safety. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11240433/

Extended Follow-Up Outcomes from Pooled Prospective ...

We analyzed data pooled from several ongoing prospective studies that are evaluating the use of Alpha DaRT for squamous cell carcinoma or basal ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05323253

A Clinical Study to Assess the Efficacy and Safety of Alpha ...

A Clinical Study to Assess the Efficacy and Safety of Alpha DaRT224 for the Treatment of Patients With Recurrent Cutaneous Squamous Cell Carcinoma.

3.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2804784

Diffusing Alpha-Emitter Radiation Therapy for Recurrent or ...

Findings This cohort study enrolled 10 patients with skin cancers who successfully underwent DaRT. Treatment was well tolerated with adverse ...

4.

jrpr.org

jrpr.org/journal/view.php?number=1171

A Comprehensive Review of Diffusing Alpha-Emitters ...

Clinical trials have shown high complete response rate in squamous cell carcinoma, with minimal side effects, suggesting DaRT's feasibility and ...

5.

redjournal.org

redjournal.org/article/S0360-3016(22)02924-8/fulltext

Long-Term Follow-Up Evaluation of Efficacy in Alpha- ...

Complete response to the Ra-224 DaRT treatment was observed in 22 lesions (22/28; 79%); 6 lesions (6/28, 21%) manifested a partial response.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10176125/

Feasibility and Safety of Diffusing Alpha-Emitter Radiation ...

This cohort study suggests the feasibility and preliminary safety of DaRT in the management of recurrent or unresectable skin cancers.

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S1120179718306434

[OA089] Diffusing Alpha-emitters Radiation Therapy (DaRT)

The Diffusing Alpha-emitters Radiation Therapy (DaRT) is a novel brachytherapy technique employing 224-Radium enriched seeds releasing short-lived alpha- ...