- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05246228
Immune System Modulation and Outcome in High-risk cSCC Treated With Surgery and Radiotherapy (HR-cSCC)
February 15, 2022 updated by: Paolo Bossi, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Immune System Modulation and Outcome in High-risk Cutaneous Squamous Cell Carcinoma Treated With Surgery and Radiotherapy: a Prospective Study
Treatment with adjuvant radiotherapy modulates immune system in many diseases as witnessed by dynamic changes of humoral and cellular immunity.
Moreover, the persistent lymphopenia after radiation therapy is a negative prognostic factor.
This study is aimed to explore the changes in immune-cell populations during radiotherapy given as adjuvant treatment for high-risk cutaneous squamous cell carcinomas and to correlate them with patient's outcome.
Study Overview
Status
Not yet recruiting
Conditions
Intervention / Treatment
Study Type
Observational
Enrollment (Anticipated)
42
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Aldo Roccaro, MD
- Phone Number: +39 0303996851
- Email: coordinamento.ricerca@asst-spedalicivili.it
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
The patients enrolled in the study are affected form cSCC classified at high risk and addressed to surgery and subsequent adjuvant radiotherapy according to clinical practice.
Description
Inclusion Criteria:
- Age ≥ 18 years.
- Signed written informed consent.
- Histologically confirmed diagnosis of cSCC.
cSCC categorized as high risk according to ASTRO Guidelines:
- close or positive margins that cannot be corrected with further surgery (secondary to morbidity or adverse cosmetic outcome).
- gross perineural spread, as identified by radiological or pathological assessment.
- disease recurrence after a prior margin-negative resection.
- pathological stage T3 and T4.
- desmoplastic or infiltrative tumors in the setting of chronic immunosuppression at pathological exam, cSCC involving regional lymphnodes, with the exception of a single, small (<3 cm) cervical lymph node harboring carcinoma, without extracapsular extension.
- cSCC addressed to adjuvant radiotherapy as per clinical practice (a complete post-operative treatment should be administered with 50-54 or 60-66 Gy depending on the margin status).
- Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2.
Exclusion Criteria:
- cSCC not eligible for surgery.
- cSCC not eligible for adjuvant radiotherapy for any condition depending on disease characteristics or patient characteristics, co-morbidities or refusal.
- Any concurrent investigational product, biologic, or hormonal therapy for cancer treatment.
- Concurrent treatment with chemotherapy for the purpose of cSCC cure.
- History or current evidence of any condition that, in the opinion of the treating investigator, might interfere with the subject's participation for the full duration of the trial.
- Any major surgery, different from that planned for the protocol, in the 15 days before the protocol starting.
- Any radiotherapy treatment in the 28 days before the protocol starting
- Pregnant or breastfeeding.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Patient with cSCC addressed to adjuvant radiotherapy as per clinical practice
The aim of the study is to evaluate patient's outcome according to the post-radiation lymphocytes count and to the changes induced in the immune cell population by a loco-regional treatment as radiotherapy.
The way to objectivate these results is to collect some blood samples and analyze them.
|
Eveluation: circulating T cells CD3+CD8+ and CD3+CD4+, absolute lymphocyte count (ALC) and neutrophil counts (ANC) and neutrophil/lymphocyte ratio (NLR), Treg lymphocytes, Naïve/Memory T lymphocytes CD4+ and CD8+,myeloid-derived suppressor cells, Plasmacytoid Dendritic Cells NK cells dimension and bright, NKT cells, Myeloid Dendritic cells, Monocytes subsets, B lymphocytes ,Analysis of plasma cytokines (TNFalpha, TGFbeta, IL-6, IL-10) by ELISA,FN signature: real-time PCR on mRNA from peripheral blood mononuclear cells (PBMCs)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease-free survival (DFS) of patients with ALC < 500 cells/mL 28 days after the end of radiotherapy treatment
Time Frame: 28 days after the end of radiotherapy treatment
|
Disease-free survival (DFS) of patients with ALC < 500 cells/mL 28 days after the end of radiotherapy treatment
|
28 days after the end of radiotherapy treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluation of changes (Δ) in the circulating immune-cells population before the start of radiotherapy and 28 days after the end of radiotherapy
Time Frame: Before and 28 days after the end of radiotherapy treatment
|
Evaluation of changes (Δ) in the circulating immune-cells population before the start of radiotherapy and 28 days after the end of radiotherapy. Correlation between DFS and circulating immune cell population |
Before and 28 days after the end of radiotherapy treatment
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Paolo Bossi, MD, ASST Spedali Civili
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Lin AJ, Gang M, Rao YJ, Campian J, Daly M, Gay H, Oppelt P, Jackson RS, Rich J, Paniello R, Zevallos J, Hallahan D, Adkins D, Thorstad W. Association of Posttreatment Lymphopenia and Elevated Neutrophil-to-Lymphocyte Ratio With Poor Clinical Outcomes in Patients With Human Papillomavirus-Negative Oropharyngeal Cancers. JAMA Otolaryngol Head Neck Surg. 2019 May 1;145(5):413-421. doi: 10.1001/jamaoto.2019.0034.
- Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol. 2018 Feb;78(2):237-247. doi: 10.1016/j.jaad.2017.08.059.
- Stratigos AJ, Garbe C, Dessinioti C, Lebbe C, Bataille V, Bastholt L, Dreno B, Fargnoli MC, Forsea AM, Frenard C, Harwood CAlpha, Hauschild A, Hoeller C, Kandolf-Sekulovic L, Kaufmann R, Kelleners-Smeets NW, Malvehy J, Del Marmol V, Middleton MR, Moreno-Ramirez D, Pellecani G, Peris K, Saiag P, van den Beuken-van Everdingen MHJ, Vieira R, Zalaudek I, Eggermont AMM, Grob JJ; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC). European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention. Eur J Cancer. 2020 Mar;128:60-82. doi: 10.1016/j.ejca.2020.01.007. Epub 2020 Feb 26.
- Stratigos AJ, Garbe C, Dessinioti C, Lebbe C, Bataille V, Bastholt L, Dreno B, Concetta Fargnoli M, Forsea AM, Frenard C, Harwood CA, Hauschild A, Hoeller C, Kandolf-Sekulovic L, Kaufmann R, Kelleners-Smeets NWJ, Malvehy J, Del Marmol V, Middleton MR, Moreno-Ramirez D, Pellecani G, Peris K, Saiag P, van den Beuken-van Everdingen MHJ, Vieira R, Zalaudek I, Eggermont AMM, Grob JJ; European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC). European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment. Eur J Cancer. 2020 Mar;128:83-102. doi: 10.1016/j.ejca.2020.01.008. Epub 2020 Feb 26.
- Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, Chung CH, Hernandez-Aya L, Lim AM, Chang ALS, Rabinowits G, Thai AA, Dunn LA, Hughes BGM, Khushalani NI, Modi B, Schadendorf D, Gao B, Seebach F, Li S, Li J, Mathias M, Booth J, Mohan K, Stankevich E, Babiker HM, Brana I, Gil-Martin M, Homsi J, Johnson ML, Moreno V, Niu J, Owonikoko TK, Papadopoulos KP, Yancopoulos GD, Lowy I, Fury MG. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med. 2018 Jul 26;379(4):341-351. doi: 10.1056/NEJMoa1805131. Epub 2018 Jun 4.
- Porceddu SV, Bressel M, Poulsen MG, Stoneley A, Veness MJ, Kenny LM, Wratten C, Corry J, Cooper S, Fogarty GB, Collins M, Collins MK, Macann AMJ, Milross CG, Penniment MG, Liu HY, King MT, Panizza BJ, Rischin D. Postoperative Concurrent Chemoradiotherapy Versus Postoperative Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck: The Randomized Phase III TROG 05.01 Trial. J Clin Oncol. 2018 May 1;36(13):1275-1283. doi: 10.1200/JCO.2017.77.0941. Epub 2018 Mar 14.
- Harris BN, Pipkorn P, Nguyen KNB, Jackson RS, Rao S, Moore MG, Farwell DG, Bewley AF. Association of Adjuvant Radiation Therapy With Survival in Patients With Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck. JAMA Otolaryngol Head Neck Surg. 2019 Feb 1;145(2):153-158. doi: 10.1001/jamaoto.2018.3650. Erratum In: JAMA Otolaryngol Head Neck Surg. 2019 Feb 1;145(2):196.
- Porceddu SV, Daniels C, Yom SS, Liu H, Waldron J, Gregoire V, Moore A, Veness M, Yao M, Johansen J, Mehanna H, Rischin D, Le QT. Head and Neck Cancer International Group (HNCIG) Consensus Guidelines for the Delivery of Postoperative Radiation Therapy in Complex Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN). Int J Radiat Oncol Biol Phys. 2020 Jul 15;107(4):641-651. doi: 10.1016/j.ijrobp.2020.03.024. Epub 2020 Apr 11.
- Carvalho HA, Villar RC. Radiotherapy and immune response: the systemic effects of a local treatment. Clinics (Sao Paulo). 2018 Dec 10;73(suppl 1):e557s. doi: 10.6061/clinics/2018/e557s.
- Bottomley MJ, Thomson J, Harwood C, Leigh I. The Role of the Immune System in Cutaneous Squamous Cell Carcinoma. Int J Mol Sci. 2019 Apr 24;20(8):2009. doi: 10.3390/ijms20082009.
- Wild AT, Ye X, Ellsworth SG, Smith JA, Narang AK, Garg T, Campian J, Laheru DA, Zheng L, Wolfgang CL, Tran PT, Grossman SA, Herman JM. The Association Between Chemoradiation-related Lymphopenia and Clinical Outcomes in Patients With Locally Advanced Pancreatic Adenocarcinoma. Am J Clin Oncol. 2015 Jun;38(3):259-65. doi: 10.1097/COC.0b013e3182940ff9.
- Kuo P, Bratman SV, Shultz DB, von Eyben R, Chan C, Wang Z, Say C, Gupta A, Loo BW Jr, Giaccia AJ, Koong AC, Diehn M, Le QT. Galectin-1 mediates radiation-related lymphopenia and attenuates NSCLC radiation response. Clin Cancer Res. 2014 Nov 1;20(21):5558-69. doi: 10.1158/1078-0432.CCR-14-1138. Epub 2014 Sep 4.
- Pike LRG, Bang A, Mahal BA, Taylor A, Krishnan M, Spektor A, Cagney DN, Aizer AA, Alexander BM, Rahma O, Balboni T, Ott PA, Hodi FS, Schoenfeld JD. The Impact of Radiation Therapy on Lymphocyte Count and Survival in Metastatic Cancer Patients Receiving PD-1 Immune Checkpoint Inhibitors. Int J Radiat Oncol Biol Phys. 2019 Jan 1;103(1):142-151. doi: 10.1016/j.ijrobp.2018.09.010. Epub 2018 Sep 15.
- Jarosz-Biej M, Smolarczyk R, Cichon T, Kulach N. Tumor Microenvironment as A "Game Changer" in Cancer Radiotherapy. Int J Mol Sci. 2019 Jun 29;20(13):3212. doi: 10.3390/ijms20133212.
- Wysong A, Newman JG, Covington KR, Kurley SJ, Ibrahim SF, Farberg AS, Bar A, Cleaver NJ, Somani AK, Panther D, Brodland DG, Zitelli J, Toyohara J, Maher IA, Xia Y, Bibee K, Griego R, Rigel DS, Meldi Plasseraud K, Estrada S, Sholl LM, Johnson C, Cook RW, Schmults CD, Arron ST. Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2021 Feb;84(2):361-369. doi: 10.1016/j.jaad.2020.04.088. Epub 2020 Apr 25. Erratum In: J Am Acad Dermatol. 2021 Jun;84(6):1796.
- Litchman GH, Fitzgerald AL, Kurley SJ, Cook RW, Rigel DS. Impact of a prognostic 40-gene expression profiling test on clinical management decisions for high-risk cutaneous squamous cell carcinoma. Curr Med Res Opin. 2020 Aug;36(8):1295-1300. doi: 10.1080/03007995.2020.1763283. Epub 2020 May 18.
- Farberg AS, Hall MA, Douglas L, Covington KR, Kurley SJ, Cook RW, Dinehart SM. Integrating gene expression profiling into NCCN high-risk cutaneous squamous cell carcinoma management recommendations: impact on patient management. Curr Med Res Opin. 2020 Aug;36(8):1301-1307. doi: 10.1080/03007995.2020.1763284. Epub 2020 May 18.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ANTICIPATED)
March 1, 2022
Primary Completion (ANTICIPATED)
November 30, 2025
Study Completion (ANTICIPATED)
December 30, 2025
Study Registration Dates
First Submitted
November 25, 2021
First Submitted That Met QC Criteria
February 15, 2022
First Posted (ACTUAL)
February 18, 2022
Study Record Updates
Last Update Posted (ACTUAL)
February 18, 2022
Last Update Submitted That Met QC Criteria
February 15, 2022
Last Verified
February 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ASST Spedali Civili di Brescia
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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