DaRT for Liver Metastases

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

Trial Summary

What is the purpose of this trial?

This is a single center study enrolling up to 10 patients. The primary objective is to Evaluate the feasibility and safety of the DaRT for the treatment of Liver Metastases. The secondary objective is to evaluate the pathological response of liver metastases according to the Modified tumor regression grade\[1\] and to evaluate the radiological response of liver metastases using the RECIST criteria.

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 data supports the effectiveness of the treatment Diffusing Alpha Radiation Emitters Therapy (DaRT) for liver metastases?

Research shows that DaRT has been effective in controlling tumors in the lungs and in treating advanced skin and head and neck cancers by using alpha particles to kill cancer cells. This suggests it might also be effective for liver metastases. ^{1 2 3 4 5}

Is DaRT generally safe for humans?

Initial studies on DaRT, which uses alpha particles to treat tumors, suggest it is feasible and safe for treating certain cancers, like squamous cell carcinomas. Safety assessments indicate that the treatment does not exceed tolerance doses in organs like the kidneys and bone marrow, even for larger tumors. ^{1 2 3 4 6}

How is the DaRT treatment for liver metastases different from other treatments?

DaRT (Diffusing Alpha Radiation Emitters Therapy) is unique because it uses alpha particles to target and kill cancer cells in solid tumors. It involves implanting sources that release alpha-emitting atoms directly into the tumor, creating a high-dose region that can effectively destroy cancer cells while minimizing damage to surrounding healthy tissue. ^{1 3 4 5 6}

Research Team

Peter Metrakos, MD

Principal Investigator

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

Eligibility Criteria

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.

My team has recommended a two-part liver surgery for my colorectal cancer spread.

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

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

Treatment Details

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.

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) 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]

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]

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]

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]

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]

2. 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]

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

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

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

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

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

Feasibility and Safety of Diffusing Alpha-Emitter Radiation Therapy for Recurrent or Unresectable Skin Cancers. [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]