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

Not Applicable
Terminated
Conditions
Breast Carcinoma
Metastatic Breast Cancer
Distant Metastases.Pathology
Invasive Breast Cancer
Registration Number
NCT03970967
Lead Sponsor
Alpha Tau Medical LTD.
Brief Summary

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

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
1
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Tumor response to DaRT9-11 weeks post DaRT insertion.

Assessment of the rate of malignant breast tumors response using the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1).

Adverse EventsDay 0 - 6 months (+/-14 days)

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

Secondary Outcome Measures
NameTimeMethod
Change in tumor volume.9-11 weeks after DaRT insertion.

Assessment of the reduction in tumor volume SUVmax based on CT/PET - CT measured tumor volume.

DaRT seeds placementDay of insertion.

Assessment of the DaRT seed placement by localization of the DaRT seed in the tumor using CT imaging.

Progression free survival6 months (+/-14 days).

Time elapsed from response to disease progression.

Change in quality of life: EORTC-QLQ-C30Day 0, 30, 70, 6 months (+/-14 days).

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).

Pathological remissions.12 weeks after DaRT seed insertion.

Assessment of (complete) pathological remissions using histopathology examination

Abscopal effects.9-11 weeks after DaRT insertion.

Assessment of abscopal effects on existing distant metastases based on PET-CT measured tumor volume.

Change in quality of life: BR23Day 0, 30, 70, 6 months (+/-14 days).

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).

Abscopal effects9-11 weeks after DaRT insertion.

Assessment of abscopal effects on existing distant metastases based on PET-CT measured SUVmax decrease compared to the primary measurement (the baseline measurement).

Trial Locations

Locations (1)

A. Tsyb Medical Radiological Research Center

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Obninsk, Kaluga Region, Russian Federation

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