Alpha Radiation Device for Advanced Pancreatic Cancer

Recruiting at 1 trial location

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

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for advanced pancreatic cancer using tiny devices that emit special radiation directly into the tumor. The goal is to see if this method is safe and effective. The radiation aims to kill cancer cells by damaging their DNA, preventing them from growing and spreading.

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 data supports the idea that Alpha Radiation Device for Advanced Pancreatic Cancer is an effective treatment?

The available research shows that Alpha Radiation Device, also known as DaRT, is effective in treating certain types of cancer. For example, it has shown a 100% response rate in patients with skin or head and neck squamous cell carcinoma. This treatment works by releasing alpha particles into the tumor, which can kill cancer cells and activate the immune system to fight the tumor. Although the studies focus on other cancers, these results suggest that DaRT could be a promising treatment for advanced pancreatic cancer as well. ^{1 2 3 4 5}

What safety data is available for the Alpha Radiation Device treatment?

The safety data for the Alpha Radiation Device, also known as Diffusing Alpha Radiation Emitters Therapy (DaRT) or Alpha DaRT, includes findings from preclinical and clinical studies. Preclinical studies have demonstrated the efficacy of DaRT in treating squamous cell carcinoma and lung tumors in mice, with safety assessments focusing on the dose delivered to distant organs. The kidneys and red bone marrow are identified as dose-limiting organs, but it is predicted that tumors weighing up to several hundred grams can be treated without exceeding tolerance doses. A 'First-in-Human' multicenter prospective trial has also reported on the feasibility and safety of DaRT for treating locally advanced and recurrent squamous cancers of the skin and head and neck, indicating its potential for clinical use. ^{2 3 4 5 6}

Is the treatment Alpha DaRT promising for advanced pancreatic cancer?

Yes, Alpha DaRT is promising for advanced pancreatic cancer. It uses tiny wires to release alpha particles directly into the tumor, which can effectively control tumor growth. When combined with chemotherapy, it has shown even better results in reducing tumor size and improving survival in studies. ^{3 4 5 6 7}

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

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

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]

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) 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]

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]

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]

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

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

3. 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]

4. 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]

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

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

6. England pubmed.ncbi.nlm.nih.gov

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

7. United States 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. [2022]