A Safety and Efficacy Study of Intra-tumoural Diffusing Alpha Radiation Emitters for the Treatment of Vulva Cancer (DaRT-V)
Primary Purpose
Vulva Cancer, Recurrent, Vulvar Squamous Cell Carcinoma, Vulva Cancer
Status
Recruiting
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
DaRT Diffusing Alpha-emitters Radiation Therapy
Sponsored by
About this trial
This is an interventional device feasibility trial for Vulva Cancer, Recurrent focused on measuring Medical Device, Brachytherapy, Diffusing Alpha-emitters
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
Sites / Locations
- Cambridge University Hospitals NHSFTRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
DaRT Diffusing Alpha-emitters Radiation Therapy
Arm Description
DaRT Diffusing Alpha-emitters Radiation Therapy using the DaRT applicator and seeds, inserted for 14 days prior to removal.
Outcomes
Primary Outcome Measures
Assess the feasibility of DaRT by the safety of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
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 Outcome Measures
Assess the efficacy of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
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
Histological evidence of necrosis in pathological lymph nodes if removed.
Assess the efficacy of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
Local control rate at 3-month and 6-month follow-up visits
Assess the efficacy of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
Patient numerical rating scale (NRS) pain score, '0' representing "no pain" to '10' representing "extreme pain"
Assess the efficacy of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
Patient mental state using the European Organisation for Research and Treatment of Cancer Quality of Life questionnaire. Scored 1-4 from 'Not at All' to 'Very Much'
Assess the efficacy of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
Percentage of necrotic tissue if residual tumour is removed surgically
Assess the efficacy of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
Patients physical state using the European Organisation for Research and Treatment of Cancer Quality of Life questionnaire. Scored 1-4 from 'Not at All' to 'Very Much'
Full Information
NCT ID
NCT04761146
First Posted
February 5, 2021
Last Updated
May 24, 2023
Sponsor
CCTU- Cancer Theme
Collaborators
Alpha Tau Medical LTD.
1. Study Identification
Unique Protocol Identification Number
NCT04761146
Brief Title
A Safety and Efficacy Study of Intra-tumoural Diffusing Alpha Radiation Emitters for the Treatment of Vulva Cancer
Acronym
DaRT-V
Official Title
A Safety and Efficacy Study of Intra-tumoural Diffusing Alpha Radiation Emitters (DaRT) for the Treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 28, 2023 (Actual)
Primary Completion Date
September 1, 2025 (Anticipated)
Study Completion Date
January 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
CCTU- Cancer Theme
Collaborators
Alpha Tau Medical LTD.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vulva Cancer, Recurrent, Vulvar Squamous Cell Carcinoma, Vulva Cancer
Keywords
Medical Device, Brachytherapy, Diffusing Alpha-emitters
7. Study Design
Primary Purpose
Device Feasibility
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
DaRT Diffusing Alpha-emitters Radiation Therapy
Arm Type
Experimental
Arm Description
DaRT Diffusing Alpha-emitters Radiation Therapy using the DaRT applicator and seeds, inserted for 14 days prior to removal.
Intervention Type
Radiation
Intervention Name(s)
DaRT Diffusing Alpha-emitters Radiation Therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Assess the feasibility of DaRT by the safety of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
Description
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)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Assess the efficacy of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
Description
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
Time Frame
Day 28 (4 weeks)
Title
To evaluate the effect DaRT on the immunological response
Description
Histological evidence of necrosis in pathological lymph nodes if removed.
Time Frame
4-6 weeks
Title
Assess the efficacy of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
Description
Local control rate at 3-month and 6-month follow-up visits
Time Frame
6 months
Title
Assess the efficacy of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
Description
Patient numerical rating scale (NRS) pain score, '0' representing "no pain" to '10' representing "extreme pain"
Time Frame
6 months
Title
Assess the efficacy of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
Description
Patient mental state using the European Organisation for Research and Treatment of Cancer Quality of Life questionnaire. Scored 1-4 from 'Not at All' to 'Very Much'
Time Frame
6 months
Title
Assess the efficacy of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
Description
Percentage of necrotic tissue if residual tumour is removed surgically
Time Frame
4-6 weeks
Title
Assess the efficacy of DaRT for the treatment of Primary and Recurrent Squamous Cell Carcinoma of the Vulva
Description
Patients physical state using the European Organisation for Research and Treatment of Cancer Quality of Life questionnaire. Scored 1-4 from 'Not at All' to 'Very Much'
Time Frame
6 months
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Eligibility based on sex assigned at birth
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Urology, Haematology and Medical Devices Team Clinical Trials Unit - Cancer Theme
Phone
01223216083
Email
cctuc@addenbrookes.nhs.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Li Tee Tan
Organizational Affiliation
Cambridge University Hospitals NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cambridge University Hospitals NHSFT
City
Cambridge
State/Province
Cambridgehire
ZIP/Postal Code
CB20QQ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Li Tee Tan, Dr.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Safety and Efficacy Study of Intra-tumoural Diffusing Alpha Radiation Emitters for the Treatment of Vulva Cancer
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