Feasibility Trial of Diffusing Alpha-emitter Radiation Therapy (DaRT) for Malignant Skin & Superficial Soft Tissue Tumors
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04377360|
Recruitment Status : Recruiting
First Posted : May 6, 2020
Last Update Posted : August 10, 2021
|Condition or disease||Intervention/treatment||Phase|
|Malignant Skin Tumor Soft Tissue Tumor, Malignant||Radiation: Diffusing Alpha-emitter Radiation Therapy||Not Applicable|
Diffusing Alpha-emitter Radiation Therapy is a form of interstitial brachytherapy which may be effective in treating malignant skin and superficial soft tissue tumors for several reasons. First, alpha-emitting radionuclides have a high linear energy transfer (LET), which produces a dense track of ionization events within cells and DNA, which produce complex DNA damage and more effective cell kill than more sparsely ionizing forms of radiation, such as gamma-rays or x-rays. Second, alpha-emitting radionuclides exhibit a higher relative biologic effect (RBE) compared to gamma-rays or x-rays, due to the relative insensitivity to cancer cellular radiosensitivity associated with cell cycling. Finally, alpha-emitting radionuclides are relatively insensitive to hypoxia, which is common as malignant skin and superficial soft tissue tumors become larger (Hall 2000).
Alpha particles have been considered unsuitable for treatment of solid tumors, since no practical method to effectively irradiate a macroscopic tumor with these short-range particles (penetration range in human tissue of ≤0.1 mm) has been found.
The "Diffusing Alpha-emitter Radiation Therapy (DaRT)", based on the interstitial intratumoral placement of an encapsulated Radium-224 source (3.7 days half-life), is described in this study. These sources release short-lived alpha-emitting atoms into the tumor microenvironment by recoil. These atoms are dispersed in the immediate surrounding tumor microenvironment both by convection through tumor interstitial fluid and by thermal diffusion. The decay of Radium-224 in the capsule results in the release of the short-lived (half-life of about 1 minute) radioisotope Radon-220. Radon-220 migrates in the tumor microenvironment until it decays. This is followed by the decay of its daughter radioisotope, Polonium-216. Lead-212, the result of this last decay, gives rise to Bismuth-212, which emits yet another alpha particle. The result of these decay events is the release of alpha particles (Kelson 1994 and Kelson 1995). DaRT will be used in this study for the treatment of malignant skin and superficial soft tissue tumors.
This study has been designed to determine the feasibility of performing the procedure required to deliver radiotherapy to the tumor. At the same time, the safety of the treatment, tumor response, radiation safety, device placement stability, and patient reported quality of life, and molecular and histologic effects on the tumor will be assessed.
The DaRT sources will be inserted using preplanned radiotherapy parameters, with a specified number and size of DaRT sources. Approximately 2-3 weeks after placement of the DaRT sources, the placement of the sources will be reassessed by volumetric imaging, and then they will be removed. Tumor response to DaRT will be assessed periodically 3 months after removal of the device.
This is a single-institution pilot feasibility trial in which 10 subjects will be enrolled.
The primary objectives are is to explore the feasibility of delivering radiotherapy for malignant skin and superficial soft tissue tumors using DaRT (Alpha Tau Medical, Tel Aviv, Israel), a form of interstitial brachytherapy which uses a novel radioisotope delivery system, as well as to determine the frequency and severity of acute adverse events. Secondary objectives will include assessments of radiotherapy-related adverse events, tumor response, radiation safety, stability of device placement, and associations with quality of life.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is a single-institution feasibility trial with DaRT for the treatment of malignant skin and superficial soft tissue tumors.|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Feasibility Trial of Diffusing Alpha-emitter Radiation Therapy (DaRT) for Malignant Skin and Superficial Soft Tissue Tumors|
|Actual Study Start Date :||January 6, 2020|
|Estimated Primary Completion Date :||November 2021|
|Estimated Study Completion Date :||December 2021|
Experimental: Diffusing Alpha-emitter Radiation Therapy (DaRT)
DaRT source will be inserted using preplanned radiotherapy parameters and reassessed by volumetric imaging 2-3 weeks after placement and then removed. Tumor response to DaRT will be assessed periodically 3 months after removal.
Radiation: Diffusing Alpha-emitter Radiation Therapy
Diffusing Alpha-emitter Radiation Therapy (DaRT) is a method of delivering interstitial brachytherapy, based on the interstitial intratumoral placement of an encapsulated Radium-224 source (3.7 days half-life). These sources release short-lived alpha-emitting atoms into the tumor microenvironment by recoil. As the radioisotope has a short half-life, the majority of radiation absorption happens in the tumor.
Other Name: DaRT
- Feasibility of DaRT Delivery [ Time Frame: 1 Day ]To explore feasibility of delivering radiotherapy for malignant skin and superficial soft tissue tumors using Diffusing Alpha-emitter Radiation Therapy (DaRT). Feasibility will be determined by successful delivery of radiation by DaRT to the malignant tumor. If an attempt to place the DaRT is unsuccessful, this patient will be considered a feasibility failure. A feasibility failure may be due to inability to execute the workflow of pre-brachytherapy imaging, treatment planning, device procurement, or technical inability to place the DaRT sources into the skin and superficial soft tissue tumor. The rate of feasibility failures will be reported.
- Frequency and Severity of Adverse Events [ Time Frame: Up to 24 Weeks after DaRT Removal ]To determine the frequency and severity of acute adverse events related to DaRT for skin and superficial soft tissue tumors. Adverse events will be assessed and graded according to Common Terminology and Criteria for adverse events (CTCAE) version 5.0.
- Rate of Tumor Response using Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: 3 Months ]To assess the rate of malignant skin and superficial soft tissue tumor response after DaRT. Tumor response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 using calibrated digital photography and CT imaging 3 months after DaRT.
- Radiation Exposure Safety using a Calibrated Survey Probe [ Time Frame: 1 Day ]To assess radiation safety through determination of patient and personnel radiation exposure during DaRT. Radiation exposure will be measured using a calibrated survey probe.
- Stability Assessment of the DaRT Sources after Placement [ Time Frame: 2 Weeks ]To assess stability of the DaRT sources after placement. Stability will be assessed by localization of the DaRT sources in the tumor after placement, measured by geometric comparisons of the DaRT sources relative to the centroid of the tumor, using brachytherapy planning software. Distance of the DaRT sources relative to the centroid immediately at the time of initial placement and immediately before removal will be analyzed and reported numerically.
- Quality of Life Assessment using the Skindex-16 [ Time Frame: 2 Weeks after DaRT Placement and 6, 12, 24 Weeks after DaRT Removal ]To assess skin-related and cancer-related quality of life (QoL) after DaRT. QoL will be assessed using the Skindex-16 following placement of the DaRT. The Skindex-16 scores range from 0 to 100 (with higher scores representing lower satisfaction).
- Quality of Life Assessment using the Skin Cancer Index (SCI) [ Time Frame: 2 Weeks after DaRT Placement and 6, 12, 24 Weeks after DaRT Removal ]To assess skin-related and cancer-related quality of life (QoL) after DaRT. QoL will be assessed using the Skin Cancer Index (SCI) following placement of the DaRT. The SCI scores range from 5-22 (with higher scores indicating higher QOL).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04377360
|Contact: Roberto Adsuaremail@example.com|
|Contact: Jessica Rodriguez||212-639-8168||RodriJ24@mskcc.org|
|United States, Iowa|
|UnityPoint Health - John Stoddard Cancer Center||Not yet recruiting|
|Des Moines, Iowa, United States, 50309|
|Contact: Shannon Benson 515-241-3305 firstname.lastname@example.org|
|Principal Investigator: Arshin Sheybani, MD|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Roberto Adsuar 212-639-8168 email@example.com|
|Contact: Jessica Rodriguez 212-639-8168 RodriJ24@mskcc.org|
|Principal Investigator: Christopher A Barker, MD|
|United States, Tennessee|
|West Cancer Center & Research Institute||Recruiting|
|Germantown, Tennessee, United States, 38138|
|Contact: Noam A. VanderWlade, MD firstname.lastname@example.org|
|Contact: Robin Patterson email@example.com|
|Principal Investigator: Noam VanderWlade, MD|
|United States, Texas|
|University Cancer & Diagnostic Center||Recruiting|
|Houston, Texas, United States, 77089|
|Contact: Mark D'Andrea, MD 713-474-1414 firstname.lastname@example.org|
|Principal Investigator: Mark D'Andrea, MD|
|United States, Washington|
|Dermatology of Seattle and Bellevue||Not yet recruiting|
|Seattle, Washington, United States, 98168|
|Contact: Elie Levy, MD 206-248-5020 email@example.com|
|Contact: Teresa Collins 206-957-4085 firstname.lastname@example.org|
|Principal Investigator: Elie Levy, MD|
|Principal Investigator:||Christopher Barker, MD||Memorial Sloan Kettering Cancer Center|