Trial Information
Status:
Open
Specialty:
Head & Neck
Date Opened:
31-03-2025
Planned Close date:
31-08-2027
Sponsors:
Cardiff University
Site Recruitment:
0 /
15
Principal Investigator:
Mr Ken McAlister
Study Title:
SCC-AFTER
Contacts
Research Nurse / Study Coordinator:
Iram Asif
Administrator:
Philippa Springle
Adjuvant Radiotherapy in Patients with High-risk Primary Cutaneous Squamous Cell Carcinoma AFTER surgery (SCC-AFTER): An Open Label, Multicentre, Two-arm Phase III Randomised trial.
Research question
In patients who have a high-risk primary cutaneous squamous cell carcinoma (HR-cSCC)
surgically excised with clear margins,is adjuvant radiotherapy plus close clinical follow-up superior
in reducing the risk of loco-regional recurrence compared with close clinical follow-up alone,and if
so,is it cost-effective?
Background
cSCC is the second most common skin cancer in the UK,with annual incidence exceeding
52,000,increasing by 6% p.a (1,2). Treatment,usually surgery,is curative in 95% (3,4).
However,5% of patients develop loco-regional recurrence (LRR) which causes 75% of cSCCspecific
mortality,substantial morbidity and reduced quality of life (QoL) (5,6). Approximately
10% of cSCC are high-risk (T2b or T3,BWH classification: 5000 p.a. in the UK) (2),with LRR
rates of 20-30% and 50%,respectively (7-11). LRR treatments have limited efficacy and
recently approved anti-PD1 immunotherapy for advanced cSCC has complete response rates
of 20% (12,13). Adjuvant radiotherapy (ART) after complete excision of HR-cSCC is used to
prevent LRR despite evidence limited to non-randomised studies (14-18). Our feasibility
surveys of UK specialist skin cancer multidisciplinary teams (SSMDTs) found widespread but
variable use of ART in HR-cSCC and simulated case-based discussions in 25 SSMDTs
identified consistent clinical equipoise for its use and support for SCC-After (19,20). Interviews
and focus groups with patients and their carers have also confirmed the importance of cSCC
recurrence and its prevention.
Aims / objectives
SCC-AFTER is an open label,multi-centre,two-arm,phase III,pragmatic group sequential
RCT to evaluate superiority,cost effectiveness and QoL impact of ART after surgery
compared to surgery alone in completely resected high-risk (BWH T2b/3) primary cSCC.
Methods
• Population: Patients (n=840) with completely excised high-risk primary cSCC (T2b/T3
by BWH staging criteria) recruited from 25 UK specialist skin cancer multidisciplinary
teams (SSMDTs).
• Intervention: ART followed by close clinical follow up
• Comparator: close clinical follow up
• Inclusion criteria: Adults aged 18 years or older,ECOG ≤3*,fit to receive RT,life
expectancy >6 months,including immunocompromised patients and people with
multiple long-term conditions (MLTC) (24)
• Exclusion criteria: cSCC on anatomic sites which interfere with suitability for ART; any
clinical or histological evidence of loco-regional cSCC.
• Primary outcom
Patients are eligible to be included in the study only if all the following inclusion criteria and none of the exclusion criteria apply:
1)
High-risk primary cSCC (T2b/T3 by BWH staging criteria) excised with adequate peripheral and deep surgical margins (according to BAD guidelines) with histologically clear margins (≥1mm by RCPath criteria). ^
2)
Time since excision surgery < 3 months (or < 4 months if necessary but < 3 months is preferred).
3)
Eastern Co-operative Oncology Group (ECOG) performance status of ≤3 at enrolment.
4)
18 years and older at time of consent.
5)
Fit for ART and able to attend radiotherapy outpatient appointments.
6)
Life expectancy > 6 months.
7)
Informed Consent obtained* which must be prior to any mandatory study-specific procedures,sampling,and analyses.
^Guidance criteria: Surgical margins: Peripheral: ≥6 mm or 10 mm,Deep: to next uninvolved anatomic surgical plane (galea on scalp). If a histological margin is close or involved,re-excision is allowed (as per BAD guidelines).
* Patients should be provided with additional support and adjustments where needed (e.g.,layering of information,involvement of a family member/friend as a support person,provide witnessed informed consent if unable to confirm informed consent in writing).
1)
High-risk primary cSCC (T2b/T3 by BWH staging criteria) excised with adequate peripheral and deep surgical margins (according to BAD guidelines) with histologically clear margins (≥1mm by RCPath criteria). ^
2)
Time since excision surgery < 3 months (or < 4 months if necessary but < 3 months is preferred).
3)
Eastern Co-operative Oncology Group (ECOG) performance status of ≤3 at enrolment.
4)
18 years and older at time of consent.
5)
Fit for ART and able to attend radiotherapy outpatient appointments.
6)
Life expectancy > 6 months.
7)
Informed Consent obtained* which must be prior to any mandatory study-specific procedures,sampling,and analyses.
^Guidance criteria: Surgical margins: Peripheral: ≥6 mm or 10 mm,Deep: to next uninvolved anatomic surgical plane (galea on scalp). If a histological margin is close or involved,re-excision is allowed (as per BAD guidelines).
* Patients should be provided with additional support and adjustments where needed (e.g.,layering of information,involvement of a family member/friend as a support person,provide witnessed informed consent if unable to confirm informed consent in writing).
1)
Any current clinicopathological evidence of loco-regional recurrence of the index tumour.
2)
Previous (within 3 years) or current non-index primary cSCC in skin drained by the same lymph node basin**.
3)
cSCC on anatomical sites which interfere with suitability for ART (such as vermilion lip,eyelids,breast,anogenital area).
4)
Patients with evidence of regional or distant disease at time of primary cSCC diagnosis.
5)
Previous radiotherapy to the same area.
6)
Patients with reproductive potential who are not willing to use contraception for the duration from trial consent until the last dose of radiotherapy if they are randomised to the ART arm.
7)
Unable to lie still unattended for the duration of ART (estimated to be around 5 minutes).
8)
Participation in another interventional clinical study that may affect the recurrence of cSCC (primary end point).
9)
History of another malignancy where metastasis could cause diagnostic uncertainty or patients receiving active systemic anti-cancer treatment (excluding hormonal treatment for prostate or breast cancer) or radiotherapy***.
**Please discuss all patients with multiple cSCC draining to the same nodal basin as the index cSCC with the SCC-After trial team including those within the last 3 years.
***Please discuss patients with malignancy of concern with the SCC-After trial team.
Any current clinicopathological evidence of loco-regional recurrence of the index tumour.
2)
Previous (within 3 years) or current non-index primary cSCC in skin drained by the same lymph node basin**.
3)
cSCC on anatomical sites which interfere with suitability for ART (such as vermilion lip,eyelids,breast,anogenital area).
4)
Patients with evidence of regional or distant disease at time of primary cSCC diagnosis.
5)
Previous radiotherapy to the same area.
6)
Patients with reproductive potential who are not willing to use contraception for the duration from trial consent until the last dose of radiotherapy if they are randomised to the ART arm.
7)
Unable to lie still unattended for the duration of ART (estimated to be around 5 minutes).
8)
Participation in another interventional clinical study that may affect the recurrence of cSCC (primary end point).
9)
History of another malignancy where metastasis could cause diagnostic uncertainty or patients receiving active systemic anti-cancer treatment (excluding hormonal treatment for prostate or breast cancer) or radiotherapy***.
**Please discuss all patients with multiple cSCC draining to the same nodal basin as the index cSCC with the SCC-After trial team including those within the last 3 years.
***Please discuss patients with malignancy of concern with the SCC-After trial team.