Vulva Cancer, Vulva Cancer, Recurrent, Vulvar Squamous Cell Carcinoma
Conditions
Keywords
Medical Device, Brachytherapy, Diffusing Alpha-emitters
Brief summary
An investigation to investigate the use of diffusing alpha-emitters radiation therapy (DaRT) for the treatment of new and recurrent squamous cell carcinoma of the vulva.
Detailed description
Squamous cell carcinoma of the vulva is a rare cancer accounting for less than 1% of female cancers. The disease predominantly affects women over the age of 65 although the incidence in younger women is rising, a finding that has been attributed to the effect of increasing human papillomavirus (HPV) infection . The standard treatment for the primary tumour is surgical excision with the aim of achieving a 1 cm clear margin on histopathology. This requires the surgeon to remove 1.5-2 cm of surrounding normal tissue to allow for shrinkage after tissue fixation. Depending on the size and location of the tumour, the surgical procedure could vary from a wide local excision to a radical vulvectomy, including excision of adjacent structures such as the clitoris, lower urethra or anus, and/or reconstructive surgery. Wound infection and breakdown are common short-term complications of radical vulva surgery. Long term consequences include functional, cosmetic, psychological and psychosexual sequelae, which can have a significant negative impact on quality of life. Recurrence rates for vulva squamous cell carcinomas range from 15% to 33%. Local recurrence in the vulva is the most common site of relapse (70%) with the groin nodes affected in 24%, pelvic nodes in 16% and distant metastases in 19%. The treatment of choice for local recurrence is surgical excision and 5-year survival rates of up to 45% have been reported. However, patients can develop multiple recurrences over a period of time and the feasibility of surgery becomes increasingly more limited as more and more tissue is removed. Brachytherapy is a form of radiotherapy where radiation sources are placed directly in contact with or into (interstitial) cancerous tissue. The radiation emitted has a short range in tissue and the brachytherapy dose distribution conforms tightly to the location of the sources with minimal dose to the surrounding healthy tissues. Alpha Tau Medical Ltd. proposes a novel treatment for malignant tumours using intra-tumoural alpha radiation, which is delivered using the Alpha DaRT Device (Alpha DaRT applicator + Alpha DaRT seeds). The technique, known as Diffusing Alpha-emitters Radiation Therapy (DaRT), combines the advantages of conventional interstitial brachytherapy with the destructive power of alpha particles.
Interventions
RADIATIONDaRT Diffusing Alpha-emitters Radiation Therapy
DaRT is a brachytherapy treatment comprising stainless-steel 316LVM wires coated with radium-224 (Alpha DaRT seeds). The radioactive seeds are inserted directly into the tumour on the perineum and will be removed after 14 days.
Sponsors
Alpha Tau Medical LTD.
CCTU- Cancer Theme
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DEVICE_FEASIBILITY
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed or recurrent (local) vulva cancer with or without distant metastases * Histopathological confirmation of squamous cell carcinoma * Macroscopic tumour in situ (i.e. tumour not excised) * Age 18 years and over * ECOG performance status 0-2 * Life expectancy more than 6 months * Willing and able to give written informed consent to participate * Measurable target according to RECIST v1.1 * Tumour size ≤ 7 centimetres in the longest diameter * Target is technically amenable for full coverage by the DaRT seeds
Exclusion criteria
* Non-squamous histology * Concomitant illnesses which may increase risk of radiation toxicity e.g. autoimmune diseases, vasculitis, etc. * Concomitant immunosuppressive and/or long-term corticosteroid treatment * Involvement in other studies that may affect evaluation of response or toxicity of DaRT in the past 30 days or 5 half-lives of the investigational product, whichever is longer * Pregnancy or breastfeeding * Women of child-bearing potential unwilling to use adequate contraception for the duration of the study and 6 months after completion (further details in CIP section 13) * Nodal recurrence without local recurrence * Previous diagnosis of other malignancy \< 3 years of enrolment (excluding non-melanomatous skin cancer) * No concurrent chemotherapy * Patients who have received prior chemotherapy or targeted therapy require a 1-month washout before DaRT insertion * Requirement to start chemotherapy within 6 weeks of DaRT insertion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the feasibility of DaRT by the safety of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva | 6 months | Measuring the feasibility of using the device by the treatment-related adverse events in the follow-up period (graded 1 'not significant' to 5 'death' with Common Terminology Criteria for Adverse Events v5.0) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the efficacy of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva | Day 28 (4 weeks) | Tumour response at 4 weeks (Day 28) after DaRT insertion as assessed by Response Evaluation Criteria in Solid Tumours (RECIST, complete response to progressive disease) criteria |
| To evaluate the effect DaRT on the immunological response | 4-6 weeks | Histological evidence of necrosis in pathological lymph nodes if removed. |
Countries
United Kingdom
Contacts
Primary ContactUrology, Haematology and Medical Devices Team Clinical Trials Unit - Cancer Theme
Outcome results
None listed