DaRT-V; CTP-VUL-00
Research type
Research Study
Full title
A Feasibility Study of Intra-tumoural Diffusing Alpha-emitters Radiation Therapy (DaRT) for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
IRAS ID
293394
Contact name
Li Tee Tan
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Trust
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
2021-000663-72, EudraCT
Duration of Study in the UK
1 years, 5 months, 31 days
Research summary
Summary of Research
Squamous cell carcinoma (SCC) of the vulva is a rare cancer predominantly affecting elderly women. Standard treatment is complete surgical excision of the primary tumour ± inguinal lymph node dissection (LND) ± post-operative (chemo)-radiation. Treatment side-effects are considerable and have significant negative impact on quality of life (QOL).
Alpha Tau Medical Ltd. has developed a novel treatment known as Diffusing Alpha-emitters Radiation Therapy (DaRT) which combines the advantages of conventional interstitial brachytherapy with the destructive power of alpha particles.
Up to now, the clinical use of alpha radiation has been limited due to its short range in tissue (a few microns). The
Alpha DaRT Device overcomes this limitation by loading Ra-224 onto thin stainless-steel wires (Alpha DaRT seeds).
When inserted into a tumour, the Ra-224 decays and releases short-lived alpha-emitting atoms into the tumour which disperse by diffusion up to several mm away.Preclinical studies have shown DaRT to be effective in various histological types. particularly SCC, while damage to adjacent normal tissue is minimal. A clinical study in patients with skin and oral cavity cancers achieved 79% complete responses and 21% partial responses with no serious adverse events. Radiation levels in patients and staff were negligible.
This is a single-centre study to evaluate the safety and efficacy of DaRT in 10 patients with new/recurrent vulva SCC.
Participants will receive DaRT as initial treatment. DaRT seeds will be inserted into the tumour and will be removed after 14 days. Response to treatment will be evaluated at 28 days after which surgical resection of residual disease and/or LND will be performed if appropriate.Primary outcome measure is treatment-related adverse events in the post-operative and follow-up period. Secondary outcome measures are tumour response at 28 days, 3/6-month local control, patient pain score, patient QOL, and necrosis in residual tumour if removed surgically.
Summary of Results
: Introduction Squamous cell carcinoma (SCC) of the vulva is a rare cancer predominantly affecting elderly women. The standard treatment for the primary tumour is surgery, but the side-effects can be considerable and may have permanent impact on patient quality-of-life (QoL). For inoperable tumours, chemo-radiation is recommended but the incidence of severe (≥G3) side effects ~50%.Diffusing Alpha-emitters Radiation Therapy (DaRT) is a novel treatment which combines the destructive power of alpha radiation with the physical advantages of interstitial brachytherapy (a form of radiotherapy where radiation sources are inserted directly into tumours). Alpha radiation has very limited penetration in tissue (a few microns) - the DaRT device overcomes this by loading Radium-224 onto thin stainless-steel wires (DaRT sources). When the DaRT sources are inserted into a tumour, short-lived alpha-emitting atoms are released which disperse by diffusion. The diffusion zone is ~5mm in tumours but in normal circulation, the atoms are rapidly washed away resulting in minimal dose to implanted normal tissue, and fewer and less severe side-effects.
The feasibility and safety of DaRT treatment was first evaluated in a study in SCC of the skin or head & neck. 28 patients were treated - 42% had received prior radiotherapy and 61% prior surgery. The response rate (RR) at 30-45 days post-insertion was 100% with 79% complete responses (CR). The rate of G2 treatment-related toxicity was 35% with no G3 toxicities. A second study in the USA of 10 patients with recurrent or unresectable skin cancers also showed a 100% objective RR (all CR) with no G3 toxicities.
Methods
The aim of the DaRT-V study was to investigate the feasibility of using DaRT to shrink vulva cancers so that less extensive surgery is required. The study was carried out at Cambridge University Hospitals (CUH). The DaRT sources were inserted under general anaesthesia (Day 0) and removed after 14 days. The primary endpoint was tolerability (completing 14-day treatment as planned). Secondary endpoints included severity of treatment-related adverse events (AEs), change in patient pain score and QoL during and after DaRT treatment, and tumour response (clinical and MRI scans) on Day 28. Study duration was 28 weeks.Results
The study opened on 28 February 2023 and closed on 13 May 2025 after 8 patients were enrolled. Median age was 70 years (range: 45-89). The longest clinical dimension at screening ranged from 25 mm to 40 mm (median: 30 mm). The longest dimension on axial MRI ranged from 14 mm to 35 mm (median: 27 mm). The median gross tumour volume (GTV) on MRI was 3.2 cc (range: 1.0-5.8 cc).All 8 participants underwent successful DaRT implantation with no complications. The first 3 patients treated were kept in hospital for a minimum of 7 days to observe for potential side-effects. The remaining patients were discharged on Day 2.
All 8 participants completed the 14-day treatment as planned. A total of 148 AEs were reported during the study period, of which 26 (17.6%) were deemed definitely, probably or possibly related to DaRT treatment. 14/26 (54%) of the DaRT-related AEs were G1 and 12 (46%) were G2. There were no G3 DaRT-related AEs. Patient-reported pain score during and after DaRT treatment remained stable. QoL scores also remained stable or improved across visits.
Six patients (75%) were assessed as having a partial response (PR) on Day 28 by the clinicians. However, none of the patients met the RECIST criteria for PR on MRI measurements. This was because although there were obvious reductions in tumour bulk in most patients on Day 28, the footprint (area of residual visible abnormality) was largely unchanged. The median reduction in GTV on MRI was -42%.The study also evaluated how easy it was to perform the DaRT procedure. Satisfactory tumour coverage with the DaRT sources was achieved in all 8 patients (median GTV coverage 92.5%; range: 82%–99%) even though none of the operators had prior experience of vulva brachytherapy. Measured doses received by operators during a single DaRT implantation were up to 0.02 mSv to the whole body and 0.4 mSv to extremities. As a comparison, the UK annual effective dose limit for radiation exposure for radiation workers is 20 mSv to whole body and 500 mSv to extremities.
Conclusion
DaRT treatment for vulva cancer is well tolerated despite the sensitive location. Although the RR is encouraging, the use of DaRT to shrink vulva cancers prior to surgery is limited by the difficulty differentiating between residual tumour and post-DaRT changes clinically and on MRI.The aim now is to assess the effectiveness of DaRT treatment for patients with different tumour types at different body locations. We will also evaluate how easy and practical it is to use the DaRT treatment in different NHS hospitals, by doctors with different backgrounds and skills.
REC name
West of Scotland REC 4
REC reference
21/WS/0096
Date of REC Opinion
13 Sep 2021
REC opinion
Further Information Favourable Opinion