Study of Metabolic Changes in the Transformation Malignant Precancerous Skin Lesions

Cutaneous Squamous Cell Carcinoma Clinical Trial

— MITOSKIN  

Official title:

Study of Metabolic Changes in the Transformation Malignant Precancerous Skin Lesions

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04389112
• Other study ID #: CHUBX 2019/3
• Status: Recruiting
• Phase: N/A
• Start date: February 28, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: November 2022
• Source: University Hospital, Bordeaux
• Contact: Marie BEYLOT-BARRY, MD, PhD
• Phone: +335 57 82 25 00
• Email: marie.beylot-barry[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Skin carcinomas are the most frequent cancers in the world, including basal cell carcinomas and cutaneous squamous cell carcinoma (cSCCs), with more than 60.000 new annual cases in France. Their incidence increases mainly due to ultraviolet (UV) exposure and population ageing. Then from 1994 to 2006, the incidence of cSCC has increased by 300%. CSCCs typically manifests as a spectrum from a precursor actinic keratosis (AK) - possible spontaneous regression at this stage- to in situ cSCC invasive cSCC and finally metastatic cSCC.

Description:

Although growing evidence indicates that bioenergetic metabolism plays an important role in the progression of tumorigenesis, little information is available on the contribution of reprogramming of energy metabolism in cancer initiation and how it influences further the bioenergetic behavior of tumors.

By applying a quantitative proteomic approach, the consortium has recently found that specific metabolic modifications precede cSCC.

This study will investigate the role of energy metabolism in malignant transformation of premalignant skin lesions into cSCC, and in cSCC progression, with correlation with clinical characteristics and metastatic outcomes. Using several cutting-edge technologies in human samples, the team will evaluate whether targeting energy metabolism has the potential to be used as curative treatments for cSCC and whether pre-determined metabolic alterations could be exploited as new preventive strategies. These modifications in energy metabolism could be used as prognostic and diagnostic biomarkers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Every patient with suspected lesion :

• AK,

• in situ cSCC,

• infiltrative cSSC

• cSCC with recurrent disease

• cSCC with cutaneous metastases.

• Patients 18 years of age or older,

• Patients with suspected AK or BCC lesions (in situ, infiltrating or metastatic),

• Patient able to sign a consent form,

• Patient affiliated with a Social Security system.

Exclusion Criteria:

• Prior systemic treatment such as checkpoint inhibitors or chemotherapy.

• Patients with cSCC or AK localized on visible zone of the face or folds

Related Conditions & MeSH terms

• Basal Cell Carcinomas
• Carcinoma
• Carcinoma, Basal Cell
• Cutaneous Squamous Cell Carcinoma

Intervention

Other:
• biopsy
Skin biopsies will be performed according to standard practices in the usual aseptic conditions, the operator wearing sterile gloves. A circular knife 3 mm will be used. Procedure interventions do not involve a drug or a device.

Locations

Country	Name	City	State
France	Hôpital Saint-André - CHU de Bordeaux	Bordeaux

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

References & Publications (4)

Hosseini M, Dousset L, Mahfouf W, Serrano-Sanchez M, Redonnet-Vernhet I, Mesli S, Kasraian Z, Obre E, Bonneu M, Claverol S, Vlaski M, Ivanovic Z, Rachidi W, Douki T, Taieb A, Bouzier-Sore AK, Rossignol R, Rezvani HR. Energy Metabolism Rewiring Precedes UVB-Induced Primary Skin Tumor Formation. Cell Rep. 2018 Jun 19;23(12):3621-3634. doi: 10.1016/j.celrep.2018.05.060. — View Citation

Hosseini M, Dousset L, Michon P, Mahfouf W, Muzotte E, Bergeron V, Bortolotto D, Rossignol R, Moisan F, Taieb A, Bouzier-Sore AK, Rezvani HR. UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis. Oncogenesis. 2019 Sep 24;8(10):52. doi: 10.1038/s41389-019-0161-z. — View Citation

Mahfouf W, Hosseini M, Muzotte E, Serrano-Sanchez M, Dousset L, Moisan F, Rachidi W, Taieb A, Rudolf J, Rezvani HR. Loss of Epidermal HIF-1a Blocks UVB-Induced Tumorigenesis by Affecting DNA Repair Capacity and Oxidative Stress. J Invest Dermatol. 2019 Sep;139(9):2016-2028.e7. doi: 10.1016/j.jid.2019.01.035. Epub 2019 Mar 13. Erratum in: J Invest Dermatol. 2022 May;142(5):1506-1507. — View Citation

Obre E, Rossignol R. Emerging concepts in bioenergetics and cancer research: metabolic flexibility, coupling, symbiosis, switch, oxidative tumors, metabolic remodeling, signaling and bioenergetic therapy. Int J Biochem Cell Biol. 2015 Feb;59:167-81. doi: 10.1016/j.biocel.2014.12.008. Epub 2014 Dec 24. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients who have a glycolysis profile (proteomic analysis liquid chromatography-mass spectrometry (LC-MS/MS))	Metabolic profiling of different stages of carcinogenesis: glycolysis, oxidative phosphorylation	Day 1
Primary	Proportion of patients who have an oxidative profile (proteomic analysis liquid chromatography-mass spectrometry (LC-MS/MS))	Metabolic profiling of different stages of carcinogenesis: glycolysis, oxidative phosphorylation	Day 1
Secondary	Evaluation of skin differentiation markers	% of samples in each category (AK, in situ, ...) that present differentiation features are assessed by immunostaining of loricrin, filaggrin, K10	Day 1
Secondary	Evaluation of cSCC aggressiveness markers	% of samples expressing aggressive markers will be assessed by evaluating the proliferation index, degree of differentiation, invasion beyond subcutaneous fat, perineural invasion, vascular invasion level of infiltration following immunohistochemistry analyses on formalin-fixed paraffin-embedded tissue sections.	Day 1
Secondary	Evaluation of skin apoptotic markers	% of samples with high apoptotic cell death level will be assessed by immunostaining using antibody against cleaved caspase-3.	Day 1
Secondary	Evaluation of mitochondrial metabolism on skin biopsies	% of samples with high mitochondrial activity will be evaluated by comparing oxygen consumption rate by different fresh samples.	Day 1
Secondary	Evaluation of cancer proliferative features on skin biopsies	% of samples that are highly proliferative will be calculated by measuring the ability of colony formation (SRB Test) and cell cycle progression (flow cytometer, western).	Day 1