To determine the histopathological response rate to neo-adjuvant nivolumab and nivolumab plus ipilimumab at time of standard of care(surgery ± radiotherapy).in patients with cutaneous squamous cell carcinoma.
This is an investigator-initiated randomized non-comparative phase II trial consisting of 40 patients with resectable stage III-IVa CSCC randomized 1:1 to ARM A: 2 courses of nivolumab 3 mg/kg in week 0 and 2, or ARM B: 2 courses of nivolumab 3 mg/kg in week 0 and 2 plus 1 course of ipilimumab 1mg/kg in week 0. Both treatment arms are neo-adjuvant and applied prior to standard of care (consisting of surgery at week 4 with or without adjuvant radiotherapy).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
3mg/kg
1mg/kg
NKI-AVL
Amsterdam, North Holland, Netherlands
Histopathological response rate at standard of care
The proportion of viable tumor cells left in the resected specimen, to neo-adjuvant nivolumab and nivolumab plus ipilimumab at time of SOC (surgery ± RT).
Time frame: At time of standard of care at week 4
Sensitivity and specificity of tumor biopsies, clinical photography, FDG-PET and (functional)MRI compared to the histopathological tumor response to neo-adjuvant immunotherapy
Histopathological tumor response to neo-adjuvant immunotherapy as measured in the tumor resection specimen will be compared to the tumor response as measured via serial tumor biopsies, the tumor biopsy at time of surgery and imaging (clinical photography, FDG-PET and (f)MRI). Histopathologic response in the tumor biopsies will be defined similarly as histopathologic response in the resected specimen. Response at imaging studies will be measured as follows: Clinical photography via specific clinical observation criteria, FDG-PET via RECIST 1.1 criteria and % change in TLG or MTV and (f)MRI via RECIST 1.1
Time frame: At time of standard of care at week 4
Numbers of participants without significant delay (>1 week) or cancelation of SOC surgery due to immune-related toxicity
Time frame: At time of standard of care at week 4
Recurrence free survival (RFS) at 2 years FU of responders versus non-responders to neo-adjuvant ICI
Time frame: At 2-years follow up
Overall survival (OS) at 2 years FU of responders versus non-responders to neo-adjuvant ICI
Time frame: At 2-years follow up
The number of patients with AE (rate and type) acoording to NCI CTCAE v.5.0 up to 2 years FU after SOC
Time frame: At 2-years follow up
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Clinical response of potentially additional AK surface areas after ICI identified by digital clinical photography on day 0, day 14, day 28 and every 6 months during FU up to 2 years.
Time frame: On day 0, day 14, day 28 (at time of surgery) and every 6 months during FU up to 2 years.
Quality of life as measured by EORTC QLQ-C30
Rated on a Likert-type scale from one (never) to four (almost always), to evaluate different domains. Functional and global health status scales indicated towards better levels of functioning, whereas higher scores in the symptom scales demonstrated higher levels of symptoms.
Time frame: At baseline, at surgery (week 4) and after 3, 6, 9, 12, 18 and 24 months during FU
Quality of life as measured by H&N 35
Rated on a Likert-type scale from one (never) to four (almost always). Multi-item scales (pain, swallowing, senses, speech, social eating, social contact, and sexuality), and six symptom items (teeth problems, opening mouth, dry mouth, sticky saliva, coughing, and feeling ill). Higher scores in the symptom scales demonstrated higher levels of symptoms.
Time frame: At baseline, at surgery (week 4) and after 3, 6, 9, 12, 18 and 24 months during FU
Quality of life as measured by the EQ5D,
Domains: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. It also includes a VAS regarding patients' "Health Today" scored between 0 and 100. Each domain will be converted into categorical values (problems vs no problems).
Time frame: At baseline, at surgery (week 4) and after 3, 6, 9, 12, 18 and 24 months during FU
Quality of life as measured by the cancer worry scale (CWS)
Rated on a Likert-type scale from one (never) to four (almost always), which were summed to produce a total CWS score ranging from 8 to 32, with higher scores indicating more frequent worries about cancer.
Time frame: At baseline, at surgery (week 4) and after 3, 6, 9, 12, 18 and 24 months during FU
Quality of life as measured by the IT questionnaire
Rated on a Likert-type scale from one (never) to four (almost always), to evaluate toxicity after immunotherapy treatment.
Time frame: At baseline, at surgery (week 4) and after 3, 6, 9, 12, 18 and 24 months during FU
Quality of life as measured by the sexuality questionnaire
Rated on a Likert-type scale from one (never) to four (almost always), to evaluate problems in sexual functioning.
Time frame: At baseline, at surgery (week 4) and after 3, 6, 9, 12, 18 and 24 months during FU