Alpha Radiation Device for Advanced Pancreatic Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by David Donath, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Alpha Tau Medical LTD.

Must not be taking: Chemotherapy, Immunotherapy, Immunosuppressants

Disqualifiers: Connective tissue disease, Autoimmune, others

No Placebo Group

Approved in 1 Jurisdiction

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.

^{1 2 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.

^{1 4 5 6 7}

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

I am 18 years old or older.

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.

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.

Trial 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)

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Centre Hospitalier de l'Université de Montréal (CHUM) Montréal, Canada

Who Is Running the Clinical Trial?

Alpha Tau Medical LTD. Lead Sponsor

References

1. 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] Diffusing alpha-emitters radiation therapy (DART) is a new form of brachytherapy enabling the treatment of solid tumors with alpha radiation. The present study examines the antitumoral effects resulting from the release of alpha emitting radioisotopes into solid lung carcinoma (LL2, A427, and NCI-H520).

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

A finite element method for modeling diffusion of alpha-emitting particles in tissue. [2023] Label="BACKGROUND" NlmCategory="BACKGROUND">Diffusing alpha-emitters Radiation Therapy ("DaRT") is a promising new modality for the treatment of solid tumors. Interstitial sources containing 224 Ra are inserted into the tumor, producing alpha particles via the decay of 224 Ra and its daughters. The alpha particles are able to produce a "kill region" of several mm due to the diffusion of the alpha-emitting atoms. The Diffusion-Leakage (D-L) model has been proposed to describe the movement of the alpha-emitters used in DaRT in tumor tissue.

3. 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] Diffusing alpha-emitters Radiation Therapy (DaRT) releases alpha-emitting atoms into the tumor microenvironment. The treatment effectively ablates human and mice xenografts and shows 100% response rates in skin or head and neck squamous cell carcinoma patients. DaRT induces specific and systemic antitumor immune activation and synergizes with immune stimulation and modulation in mice. Here, the transcriptional profile activated by DaRT, and its potential to enhance responsiveness to immune checkpoint inhibition by programmed cell death protein 1 (PD-1) blockade were studied.

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] Our purpose was to report the feasibility and safety of diffusing alpha-emitter radiation therapy (DaRT), which entails the interstitial implantation of a novel alpha-emitting brachytherapy source, for the treatment of locally advanced and recurrent squamous cancers of the skin and head and neck.

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

The low-LET radiation contribution to the tumor dose in diffusing alpha-emitters radiation therapy. [2023] Label="BACKGROUND" NlmCategory="BACKGROUND">Diffusing alpha-emitters Radiation Therapy ("Alpha DaRT") is a new technique that enables the use of alpha particles for the treatment of solid tumors. Alpha DaRT employs interstitial sources carrying a few μCi of 224 Ra below their surface, designed to release a chain of short-lived atoms (progeny of 224 Ra) which emit alpha particles, along with beta, Auger, and conversion electrons, x- and gamma rays. These atoms diffuse around the source and create-primarily through their alpha decays-a lethal high-dose region measuring a few millimeters in diameter.

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] Diffusing alpha-emitters radiation therapy (DART) is a proposed new form of brachytherapy, allowing the treatment of solid tumors by alpha particles. DART utilizes implantable sources carrying small activities of radium-224, which continually release into the tumor radon-220, polonium-216 and lead-212 atoms, while radium-224 itself remains fixed to the source. The released atoms disperse inside the tumor by diffusive and convective processes, creating, through their alpha emissions, a high-dose region measuring several mm in diameter about each source. The efficacy of DART has been demonstrated in preclinical studies on mice-borne squamous cell carcinoma and lung tumors and the method is now being developed toward clinical trials. This work studies DART safety with respect to the dose delivered to distant organs as a result of lead-212 leakage from the tumor through the blood, relying on a biokinetic calculation coupled to internal dose assessments. It is found that the dose-limiting organs are the kidneys and red bone marrow. Assuming a typical source spacing of approximately 5 mm and a typical radium-224 activity density of 0.4-0.8 MBq g(-1) of tumor tissue, it is predicted that tumors weighing up to several hundred grams may be treated without reaching the tolerance dose in any organ.

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] We developed (224)Ra-loaded wires that when inserted into solid tumors, release radioactive atoms that spread in the tumor and irradiate it effectively with alpha particles (diffusing alpha-emitters radiation therapy [DaRT]). In this study, we tested the ability of intratumoral (224)Ra-loaded wires to control the local growth of pancreatic tumors and the enhancement of this effect by chemotherapy. Pancreatic mouse tumors (Panc02) were treated with (224)Ra-loaded wire(s) with or without gemcitabine. The tumor size and survival were monitored, and autoradiography was performed to evaluate the spread of radioactive atoms inside the tumor. Mouse and human pancreatic cancer cells, irradiated in vitro by alpha particles with or without chemotherapy, were evaluated for cell growth inhibition. The insertion of (224)Ra-loaded wires into pancreatic tumors in combination with gemcitabine achieved significant local control and was superior to each treatment alone. A dosimetric analysis showed the spread of radioactive atoms in the tumor around the wires. Alpha particles combined with gemcitabine or 5-FU killed mouse and human cells in vitro better than each treatment alone. DaRT in combination with gemcitabine was proven effective against pancreatic tumors in vivo and in vitro, and the process may be applicable as a palliative treatment for patients with pancreatic cancer.