a safety and efficacy study of intra-tumoural diffusing alpha radiation emitters for the treatment of vulva cancer

Conditions: Vulva Cancer, Recurrent; Vulvar Squamous Cell Carcinoma; Vulva Cancer

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.

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

Keywords: medical device brachytherapy diffusing alpha-emitters