A Safety and Efficacy Study of Intra-tumoural Diffusing Alpha Radiation Emitters for the Treatment of Vulva Cancer

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.

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.

Eligibility Criteria:
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