Alpha Radiation Emitters Device for the Treatment of Newly Diagnosed Breast Carcinoma Patients With Distant Metastases

A Safety and Effectiveness Study of Intratumoral Diffusing Alpha Radiation Emitters for the Treatment of Newly Diagnosed Breast Carcinoma Patients With Distant Metastases

A unique approach for cancer treatment employing intratumoral diffusing alpha radiation emitter device for newly Diagnosed Breast Carcinoma patients with distant metastases

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer; Breast Carcinoma; Invasive Breast Cancer; Distant Metastases.Pathology
• Intervention / Treatment: Device: Device: Radiation: Diffusing Alpha Radiation Emitters Therapy (DaRT)

Detailed Description

This will be a prospective, open label, single arm, controlled study, assessing the safety and efficacy of diffusing alpha emitters radiation therapy (DaRT) delivered through radioactive sources [Ra-224 containing stainless-steel 316LVM tubes- (Alpha DaRT seeds)] inserted into malignant breast lesions.

This approach combines the advantages of local intratumoral irradiation of the tumor, as used in conventional brachytherapy, with the power of the alpha radiation emitting atoms, that will be introduced in quantities considerably lower than radiation therapy already used in patients.

Histopathological confirmed invasive breast tumors with no involvement of skin will be treated using DaRT seeds.

The primary effectiveness endpoint of the study is the tumor response to DaRT treatment assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) 9-11 weeks after DaRT seed insertion.

Safety will be assessed by the cumulative frequency, severity and causality of acute adverse events related to the DaRT treatment of adverse events (AEs) observed including the follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Kaluga Region
    • Obninsk, Kaluga Region, Russian Federation, 249036
      • A. Tsyb Medical Radiological Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects with histopathological confirmation of primary (or recurrent) invasive breast carcinoma and distant metastatic disease at diagnosis.
• Target tumor size ≤ 3.0 cm (T1-2b category);
• Morphological type: invasive breast cancer
• Luminal-type A (ER+, PR+, Her2/neu +1), HER+, luminal-type B (ER +/-, PR +/-, Her2/neu+1), or Triple negative breast carcinoma
• Measurable disease according to RECIST v1.1.
• Subjects over 45 years old.
• Subjects' ECOG Performance Status Scale is < 2.
• Subjects' life expectancy more than 6 months.
• Platelet count ≥100,000/mm3.
• International normalized ratio of prothrombin time ≤1.8.
• Creatinine ≤1.9 mg/dL.
• Women of childbearing potential (WOCBP) will have evidence of negative pregnancy test.
• Subjects are willing to sign an informed consent form.

Exclusion Criteria:

• T4 category with skin involvement.
• Regional lymph node metastases.
• Ductal carcinoma in situ.
• Inflammatory breast carcinoma.
• Patients with pre-irradiation of the breast.
• Acute infection disease.
• The presence of HIV, RW, HbsAg, HCV in the acute stage.
• Pregnancy or lactation.
• Serious competing (somatic) diseases incompatible according to the researcher with brachytherapy.
• Mental illness.
• Patients undergoing immunosuppressive and/or systemic corticosteroid treatment
• 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.
• High probability of protocol non-compliance (in opinion of investigator).
• Patients with significant comorbidities that the treating physician deems may conflict with the endpoints of the study (e.g., poorly controlled autoimmune diseases, vasculitis, etc.)
• Subjects not willing to sign an informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DaRT Seeds; Intratumoral Diffusing alpha-emitters Radiation Therapy (DaRT) Seeds	Device: Device: Radiation: Diffusing Alpha Radiation Emitters Therapy (DaRT); An intratumoral insertion of radioactive sources [Ra-224 containing stainless-steel 316LVM tubes- (Alpha DaRT seeds)]. The seeds release by recoil into the tumor short-lived alpha-emitting atoms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response to DaRT	Assessment of the rate of malignant breast tumors response using the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1).	9-11 weeks post DaRT insertion.
Adverse Events	Assessment of the frequency, severity and causality of acute adverse events related to the DaRT treatment using the Common Terminology and Criteria for adverse events (CTCAE) version 5.0	Day 0 - 6 months (+/-14 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in tumor volume.	Assessment of the reduction in tumor volume SUVmax based on CT/PET - CT measured tumor volume.	9-11 weeks after DaRT insertion.
DaRT seeds placement	Assessment of the DaRT seed placement by localization of the DaRT seed in the tumor using CT imaging.	Day of insertion.
Change in quality of life: EORTC-QLQ-C30	Assessment of patient reported health-related Quality of Life (QoL) outcomes after DaRT treatment, using QoL questionnaires EORTC-QLQ-C30. Scale range in score from 0 (best) to 100(worst).	Day 0, 30, 70, 6 months (+/-14 days).
Progression free survival	Time elapsed from response to disease progression.	6 months (+/-14 days).
Pathological remissions.	Assessment of (complete) pathological remissions using histopathology examination	12 weeks after DaRT seed insertion.
Abscopal effects.	Assessment of abscopal effects on existing distant metastases based on PET-CT measured tumor volume.	9-11 weeks after DaRT insertion.
Change in quality of life: BR23	Assessment of patient reported health-related Quality of Life (QoL) outcomes after DaRT treatment, using QoL questionnaires BR23. Scale range in score from 0 (best) to 100(worst).	Day 0, 30, 70, 6 months (+/-14 days).
Abscopal effects	Assessment of abscopal effects on existing distant metastases based on PET-CT measured SUVmax decrease compared to the primary measurement (the baseline measurement).	9-11 weeks after DaRT insertion.

Collaborators and Investigators

• Sponsor: Alpha Tau Medical LTD.
• Investigators: Principal Investigator: Aleksandr Obukhov, A. Tsyb Medical Radiological Research Centre, (A. Tsyb MRRC), Obninsk, Russia

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2019
• Primary Completion (Actual): November 30, 2023
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: May 31, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: HER2; Breast cancer; Metastatic breast cancer; Alpha radiation; Triple negative; Luminal A; Invasive breast cancer; Luminal B; Breast carcinoma; Breast metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Breast Diseases; Neoplastic Processes; Breast Neoplasms; Carcinoma; Neoplasm Metastasis
• Other Study ID Numbers: CTP-BRST-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No