Alpha Radiation Device for Advanced Pancreatic Cancer

Recruiting at 3 trial locations

Overseen By Liron Dimnik

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Alpha Tau Medical LTD.

Must not be taking: Chemotherapy, Immunotherapy, Immunosuppressants

Disqualifiers: Connective tissue disease, Autoimmune, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for advanced pancreatic cancer using a device that emits alpha radiation directly into the tumor. The goal is to determine if this approach can effectively target and reduce the cancer. It is intended for individuals with advanced pancreatic cancer that has spread too far for surgical removal or for those not healthy enough for surgery. Participants should have a noticeable tumor no larger than 4 cm. This trial offers a potential option for those with limited treatment choices due to the advanced stage of their cancer. As an unphased trial, it provides an opportunity to explore innovative treatment options that might not be available elsewhere.

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

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 taking concomitant chemotherapy or immunotherapy.

What prior data suggests that this device is safe for treating advanced pancreatic cancer?

Research has shown that Diffusing Alpha Radiation Emitters Therapy (DaRT) holds promise for treating advanced pancreatic cancer. In one study, all patients successfully received the treatment, and early results suggested it was safe. Another study found DaRT both feasible and safe for patients whose cancer cannot be surgically removed.

These findings are encouraging, indicating the treatment is generally well-tolerated. So far, these studies have reported no major safety concerns, suggesting that DaRT could be a safe option for people with advanced pancreatic cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for advanced pancreatic cancer, which typically include chemotherapy and radiation therapy, the Diffusing Alpha Radiation Emitters Therapy (DaRT) uses a new approach by delivering alpha radiation directly into the tumor via DaRT seeds. This method targets cancer cells more precisely while minimizing damage to surrounding healthy tissues. Researchers are excited because this targeted approach may lead to fewer side effects and potentially improve the effectiveness of treatment, offering new hope for patients with limited options.

What evidence suggests that this device is effective for advanced pancreatic cancer?

Research shows that Diffusing Alpha Radiation Emitters Therapy (DaRT), which participants in this trial will receive, can effectively treat advanced pancreatic cancer. Studies have found that DaRT delivers focused radiation directly to tumors, killing cancer cells while protecting nearby healthy tissue. A thorough review highlights DaRT's effectiveness and fewer side effects compared to traditional radiation. Early data suggest that this method is both practical and safe for pancreatic tumors. While more research is needed, DaRT's targeted approach offers hope for treating this challenging cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

David Donath, MD

Principal Investigator

Brachytherapy Service Centre Hospitalier de l'Université de Montreal

Corey Miller, MD

Principal Investigator

Division of Gastroenterology, Jewish General Hospital

Are You a Good Fit for This Trial?

Adults over 18 with advanced pancreatic cancer that can't be removed by surgery due to its spread or patient's health. They must have a life expectancy of at least 12 weeks, an ECOG performance status ≤ 2 (meaning they are up and about more than half the day), and a tumor no larger than 4cm. Pregnant women, those unwilling to consent, or patients with certain serious diseases cannot participate.

Inclusion Criteria

You are expected to live for at least 12 more weeks.

My cancer is advanced or has spread and is a type of pancreatic cancer.

My largest cancer area is 4cm or smaller.

Exclusion Criteria

I am not pregnant or breastfeeding.

You have other health conditions that might affect the goals of the study, such as autoimmune diseases or vasculitis.

I am not on long-term immunosuppressive drugs, except for short-term steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

DaRT Insertion

Eligible patients undergo the procedure of DaRT seeds insertion

1 day

1 visit (in-person)

Acute Follow-up

Participants are monitored for acute adverse events and short-term effects

4-6 weeks

Multiple visits (in-person)

Long-term Follow-up

Participants are monitored for long-term safety and effectiveness, including overall survival and stent durability

24 months

Periodic visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Diffusing Alpha Radiation Emitters Therapy (DaRT)

Trial Overview The trial is testing DaRT, a new type of radiation therapy placed directly into the tumor in patients with advanced pancreatic cancer. It aims to see how well this local treatment works on tumors that can't be surgically removed.

How Is the Trial Designed?

Group I: DaRT Seeds Experimental Treatment 1 Intervention

Intratumoral Diffusing alpha-emitters Radiation Therapy (DaRT) Seeds

Diffusing Alpha Radiation Emitters Therapy (DaRT) is already approved in Canada for the following indications:

Approved in Canada as Alpha DaRT for:

• Advanced pancreatic cancer

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) 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]

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]

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]

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]

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]

The study demonstrated that (224)Ra-loaded wires effectively control the growth of pancreatic tumors in mice, especially when combined with the chemotherapy drug gemcitabine, leading to better outcomes than either treatment alone.

In vitro experiments showed that alpha particles from the (224)Ra wires, when used with gemcitabine or 5-FU, significantly inhibited the growth of both mouse and human pancreatic cancer cells, suggesting a promising palliative treatment approach for pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local control of experimental malignant pancreatic tumors by treatment with a combination of chemotherapy and intratumoral 224radium-loaded wires releasing alpha-emitting atoms. Horev-Drori, G., Cooks, T., Bittan, H., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06698458

Study Details | NCT06698458 | Alpha Radiation Emitters ... The primary objective of the study is to evaluate the safety of Alpha DaRT in combination with chemotherapy, based on the cumulative incidence rate, severity ...

2. alphatau.com alphatau.com/single-post/alpha-tau-successfully-treats-first-patient-in-its-u-s-multi-center-pancreatic-cancer-clinical-tria

Alpha Tau Successfully Treats First Patient in its U.S. Multi ... Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) is designed to enable highly potent and conformal alpha-irradiation of solid tumors by ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11469937/

Feasibility and safety of endoscopic ultrasound-guided ... Feasibility and safety of endoscopic ultrasound-guided diffusing alpha emitter radiation therapy for advanced pancreatic cancer: Preliminary data

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

A Comprehensive Review of Diffusing Alpha-Emitters ... DaRT emerges as a highly localized cancer treatment method with minimal side effects compared to traditional radiation therapy.

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/564715

Alpha Radiation Emitters Device (DaRT) for the Treatment ... A Safety Study of Intratumoral Diffusing Alpha Radiation Emitters With Chemotherapy for the Treatment of Locally Advanced Pancreatic Cancer. Estimated trial ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05657743

A Feasibility and Safety Study of Intratumoral Diffusing ... The study is designed to evaluate the feasibility and safety of the DaRT seeds for the treatment of advanced pancreatic cancer. The study will be comprised of a ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39398444/

Feasibility and safety of endoscopic ultrasound-guided ... Preliminary results from this first-in-human trial indicate that EUS-guided Alpha DaRT treatment for unresectable pancreatic cancer is feasible and safe.

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.741

Interim analysis of feasibility, safety, and tumor control in ... Successful placement of Alpha DaRT sources into the targetable pancreatic lesions was achieved in all cases (100%), as confirmed by post- ...