DaRT for Liver Metastases

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: Immunosuppressants, others

Disqualifiers: Concurrent cancer, Cardiovascular disease, Brain metastases, 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

Duration: Immediate

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Diffusing Alpha Radiation Emitters Therapy (DaRT) for liver metastases, which are cancerous growths in the liver that have spread from the colon or rectum. The main goal is to assess the safety and feasibility of DaRT for treating these liver tumors. Researchers also aim to evaluate the cancer's response to the treatment using imaging techniques. Individuals referred for a two-stage liver surgery to remove metastatic colorectal cancer might be suitable candidates for this trial. As an unphased trial, this study offers patients the chance to contribute to groundbreaking research that could lead to new treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, patients on systemic immunosuppressive therapy are excluded, except for brief use of corticosteroids. If you are on anticoagulants like Coumadin or heparin, you can participate if there are no underlying abnormalities.

What prior data suggests that DaRT is safe for treating liver metastases?

Research has shown that Diffusing Alpha Radiation Emitters Therapy (DaRT) has promising safety results from earlier studies. These studies found that DaRT is generally well-tolerated by patients, with most side effects being mild and manageable. Data from several clinical trials suggest that DaRT can target tumors with radiation without significantly harming nearby healthy tissues. This targeted approach helps reduce potential side effects.

While detailed safety results for liver metastases are still under investigation, previous research in other cancer types has shown strong long-term safety, with serious unexpected side effects being rare. The therapy focuses solely on the tumor, which helps lower the risks usually linked to radiation treatments.

Although more research is needed to confirm these findings for liver metastases, current data provide a strong basis for its safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Diffusing Alpha Radiation Emitters Therapy (DaRT) for liver metastases because it introduces a novel way to treat tumors directly. Unlike traditional options like chemotherapy and radiation therapy, which can affect the entire body, DaRT uses intratumoral seeds to deliver alpha radiation precisely to the tumor itself. This method not only targets cancer cells more accurately, potentially sparing healthy tissue, but also harnesses alpha particles, which have a high ability to damage cancer cells effectively. This targeted approach could lead to fewer side effects and improved outcomes for patients with liver metastases.

What evidence suggests that DaRT is effective for liver metastases?

Research shows that Diffusing Alpha Radiation Emitters Therapy (DaRT), which participants in this trial will receive, could help treat cancer that has spread to the liver. Studies have found that DaRT can directly target and deliver radiation to cancer cells. Early experiments suggest that DaRT might shrink tumors using a special kind of radiation. Initial results indicate that it is generally safe and effective in reaching liver tumors. Although more research is needed, these early findings are promising for those considering this treatment option. ^{1 2 3 6 7}

Who Is on the Research Team?

Peter Metrakos, MD

Principal Investigator

McGill University Health Centre/Research Institute of the McGill University Health Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 with liver metastases from colorectal cancer, who are planned for a two-stage hepatectomy. Participants must have adequate liver function, visible and measurable lesions by CT scan, an ECOG performance status of ≤2 (meaning they can care for themselves), and a life expectancy of at least 12 weeks.

Inclusion Criteria

My liver cancer can be seen and measured on a CT scan.

My cancer can be fully treated with Alpha DaRT Seeds.

Subjects' life expectancy is at least 12 weeks

Exclusion Criteria

I have another type of cancer, but it's either treated, has a good prognosis, or was cured over 3 years ago.

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

Contraindication to angiography: Any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agent, Severe peripheral vascular disease precluding catheterization, History of severe allergy or intolerance to contrast agents, narcotics, sedatives or atropine that cannot be managed medically, Known hypersensitivity to any of the components of the treatment, Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 12 months, Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry, Brain metastases, Active clinically serious infections, Major surgery within 4 weeks of start of the study therapy, Patients with uncontrolled intercurrent illnesses including, but not limited to an active infection requiring systemic therapy or a known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial or interfere with the study endpoints, Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study, High probability of protocol non-compliance (in opinion of investigator), Pregnant or breastfeeding women, Volunteers participating in another interventional study in the past 30 days which might conflict with the endpoints of this study or the evaluation of response or toxicity of DaRT

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Intratumoral Diffusing Alpha-emitters Radiation Therapy (DaRT) Seeds for the treatment of liver metastases

Immediate

1 visit (in-person) for DaRT insertion

Follow-up

Participants are monitored for safety and effectiveness after DaRT treatment

24 months

Regular visits for safety assessments and imaging

Pathological and Radiological Assessment

Evaluation of pathological and radiological response to DaRT treatment

7-9 weeks post DaRT insertion

1 visit (in-person) for assessment

What Are the Treatments Tested in This Trial?

Interventions

• Diffusing Alpha Radiation Emitters Therapy (DaRT)

Trial Overview The study is testing the safety and feasibility of DaRT—Diffusing Alpha Radiation Emitters Therapy—for treating liver metastases. It will also assess how well the tumors respond to this treatment both pathologically, using tumor regression grading, and radiologically with RECIST criteria.

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

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) 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 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]

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]

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) 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05829291

Alpha Radiation Emitters Device for the Treatment of Liver ... This study is a Prospective, Open label, one arm, single center study to evaluate the feasibility and safety of Diffusing Alpha Radiation Emitters for the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12483980/

Diffusing alpha‐emitters radiation therapy: In vivo ... This study presented results from preclinical in vivo experiments with Alpha‐DaRT for the purpose of providing a reasonably informed starting ...

3. trialx.com trialx.com/clinical-trials/listings/273323/alpha-radiation-emitters-device-for-the-treatment-of-liver-metastases-dart/

Alpha Radiation Emitters Device for the Treatment of Liver ... This study is a Prospective, Open label, one arm, single center study to evaluate the feasibility and safety of Diffusing Alpha Radiation ...

4. alphatau.com alphatau.com/single-post/health-canada-authorization-for-alpha-dart-clinical-trial-for-the-treatment-of-liver-metastases

Health Canada Authorization for Alpha DaRT Clinical Trial ... The study primarily aims to examine the feasibility of delivering Alpha DaRT sources into the liver metastases, as well as the safety of ...

5. biospace.com biospace.com/press-releases/alpha-tau-announces-cornerstone-interim-data-across-multiple-clinical-trials-to-be-shared-at-r-d-update-day

Alpha Tau Announces Cornerstone Interim Data Across ... A 100% success rate was achieved in delivering the Alpha DaRT sources (feasibility), and strong safety results were observed: 151 adverse events ...

6. alphatau.com alphatau.com/single-post/alpha-tau-announces-robust-long-term-safety-and-efficacy-data-from-multiple-clinical-trials-of-alpha

Alpha Tau Announces Robust Long-Term Safety and ... Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) is designed to enable highly potent and conformal alpha-irradiation of solid tumors by ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0360301624017085

2942 Toward a Clinical Trial in the Human Liver: Effect of ... In this study we evaluated the feasibility of Alpha DaRT in treating a liver colorectal metastasis. We hypothesized that a single Alpha DaRT ...