A prospective study investigating the efficacy and toxicity of definitive ChemoRadiation and ImmunOtherapy (CRIO) in locally and/or regionally advanced unresectable cutaneous squamous cell carcinoma.
Antibodies, Monoclonal
/ therapeutic use
Australia
Carcinoma, Squamous Cell
/ therapy
Chemoradiotherapy
/ methods
Combined Modality Therapy
/ methods
Humans
Immunotherapy
/ methods
Lymphatic Metastasis
Neoplasm Metastasis
Positron Emission Tomography Computed Tomography
Progression-Free Survival
Prospective Studies
Receptors, CXCR4
/ metabolism
Skin Neoplasms
/ therapy
Treatment Outcome
Curative
Immunotherapy
Radiotherapy
SCC
Skin cancer
Journal
Radiation oncology (London, England)
ISSN: 1748-717X
Titre abrégé: Radiat Oncol
Pays: England
ID NLM: 101265111
Informations de publication
Date de publication:
09 Apr 2021
09 Apr 2021
Historique:
received:
03
10
2020
accepted:
23
03
2021
entrez:
10
4
2021
pubmed:
11
4
2021
medline:
21
12
2021
Statut:
epublish
Résumé
Patients with unresectable advanced cutaneous squamous cell carcinoma (cSCC) are generally treated with palliative intent. Immune checkpoint blockade has significant activity in the palliative setting in patients with recurrent or metastatic cSCC. This single arm phase 2 prospective study aims to investigate the combination of curative intent chemoradiation and durvalumab (anti-PD-L1 checkpoint inhibitor) for this patient cohort. Patients with unresectable locally and or regionally advanced pathologically confirmed cSCC (stage III-IVa) deemed fit for CRIO by consensus of the Multidisciplinary meeting will be eligible. In the first stage of a two-stage minimax design, we aim to recruit a total of 15 patients. If fewer than 7 patients achieved a complete response in the first stage, we will conclude the treatment is not more effective than standard treatment. The co-primary endpoints of CRIO are the safety of treatment (acute and late toxicities) and the rate of complete response. Secondary endpoints would include overall survival, progression free survival, and locoregional control. Translational research endpoints including biomarkers (CD73, CD39, PD-1, PD-L1) will also be explored utilising multiplex immunohistochemistry on tumour biopsy samples obtained prior to commencing treatment and during treatment (week 2). In addition, the utility of CXCR-4 PET/CT scan will be explored. CRIO is a novel trial evaluating the combination of curative intent chemoradiotherapy with concurrent and adjuvant durvalumab for patients with unresectable stage III-IVa cSCC. Trial registered with the Australian New Zealand Clinical Trial Registry (ACTRN12618001573246).
Sections du résumé
BACKGROUND
BACKGROUND
Patients with unresectable advanced cutaneous squamous cell carcinoma (cSCC) are generally treated with palliative intent. Immune checkpoint blockade has significant activity in the palliative setting in patients with recurrent or metastatic cSCC. This single arm phase 2 prospective study aims to investigate the combination of curative intent chemoradiation and durvalumab (anti-PD-L1 checkpoint inhibitor) for this patient cohort.
METHODS
METHODS
Patients with unresectable locally and or regionally advanced pathologically confirmed cSCC (stage III-IVa) deemed fit for CRIO by consensus of the Multidisciplinary meeting will be eligible. In the first stage of a two-stage minimax design, we aim to recruit a total of 15 patients. If fewer than 7 patients achieved a complete response in the first stage, we will conclude the treatment is not more effective than standard treatment. The co-primary endpoints of CRIO are the safety of treatment (acute and late toxicities) and the rate of complete response. Secondary endpoints would include overall survival, progression free survival, and locoregional control. Translational research endpoints including biomarkers (CD73, CD39, PD-1, PD-L1) will also be explored utilising multiplex immunohistochemistry on tumour biopsy samples obtained prior to commencing treatment and during treatment (week 2). In addition, the utility of CXCR-4 PET/CT scan will be explored.
DISCUSSION
CONCLUSIONS
CRIO is a novel trial evaluating the combination of curative intent chemoradiotherapy with concurrent and adjuvant durvalumab for patients with unresectable stage III-IVa cSCC.
TRIAL REGISTRATION
BACKGROUND
Trial registered with the Australian New Zealand Clinical Trial Registry (ACTRN12618001573246).
Identifiants
pubmed: 33836800
doi: 10.1186/s13014-021-01795-5
pii: 10.1186/s13014-021-01795-5
pmc: PMC8033693
doi:
Substances chimiques
Antibodies, Monoclonal
0
CXCR4 protein, human
0
Receptors, CXCR4
0
durvalumab
28X28X9OKV
Types de publication
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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