Prognostic Role of Inhibitor of Apoptosis Protein Overexpression on Recurrence Rate in Cervical Cancer

Cancer of Cervix Clinical Trial

— EPIcol  

Official title:

Evaluation of the Prognostic Role of Inhibitor of Apoptosis Protein Overexpression on the 24-month Recurrence Rate in Locally Advanced Cervical Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06147960
• Other study ID #: NIMAO/2023-1/FF-01
• Status: Not yet recruiting
• Start date: November 2023
• Est. completion date: November 2024

Study information

• Verified date: November 2023
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: Frédéric FITENI, Dr.
• Phone: +334.34.03.46.69
• Email: frederic.fiteni[@]chu-nimes.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Overexpression of inhibitors of apoptosis proteins (IAPs) in patients treated for locally advanced cervical cancer with exclusive radio-chemotherapy may have a prognostic role on the local recurrence rate at 24 months.

Description:

Cervical cancer remains one of the most common cancers in women in terms of both incidence and mortality. Human Papilloma Virus carriage is a necessary condition for the development of these cancers but is not the only factor responsible for malignant transformation. Numerous molecular alterations come into play in the development of these tumours, involving the activation of oncogenes or the inactivation of tumour suppressor genes. Treatment of locally-advanced cancer is based on radiotherapy or a combination of radiotherapy and chemotherapy. Responses to anti-neoplastic treatments remain very heterogeneous from one woman to another. Predicting the response to these treatments would make it possible to envisage early therapeutic alternatives for patients identified as not very sensitive to standard treatments. IAPs (inhibitors of apoptosis proteins), which include XIAP, cIAP1 and cIAP2, are proteins involved in many cancers and capable of downregulating tumour cell apoptosis. It seems justified to investigate the role of these IAPs in resisting apoptosis-inducing anti-neoplastic treatments such as chemotherapy or radiotherapy. The aim of our study is to assess the prognostic role of overexpression of IAPs in locally advanced cervical cancer treated exclusively with radio-chemotherapy. This research seems all the more important as IAP-inhibiting molecules are currently being studied in other types of cancer (ear, nose and throat cancers) and appear to have a very encouraging radiosensitising effect. The hypothesis is that overexpression of IAPs in patients treated for locally advanced cervical cancer with exclusive radio-chemotherapy has a prognostic role on the local recurrence rate at 24 months.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 180
• Est. completion date: November 2024
• Est. primary completion date: May 2024
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients treated with the exclusive radio-chemotherapy combination for locally advanced cervical carcinoma (stage Ib-IVb according to FIGO classification).
• Patients aged = 18 years.
• Patients with a minimum of 2 years post-treatment follow-up.
• Patients for whom the initial biopsy specimen (before treatment) is available.
• Patients who have not indicated that they do not wish to participate in the study.
• Patients affiliated to or benefiting from a health insurance scheme.

Exclusion Criteria:

• Patients under court protection, guardianship or curatorship.

Related Conditions & MeSH terms

• Apoptosis
• Cancer of Cervix
• Recurrence
• Uterine Cervical Neoplasms

Intervention

Diagnostic Test:
• Immunohistochemistry
Blocks containing formalin-fixed, paraffin-embedded (FFPE) biopsies will be used to analyse the expression of XIAP, cIAP1 and cIAP2 proteins by immunohistochemistry. The antibodies will be selected on the basis of the literature and their validation for this technology (Schnoell et al. 2020). The immunohistochemical techniques will be performed on an automated immunolabelling machine (DakoLink®) after antigen demasking. The specific binding of primary antibodies will be revealed by the application of Flex reagent (Dako Agilent), a dextran polymer coupled on the one hand to anti-mouse and anti-rabbit immunoglobulins, and on the other hand to a large number of horseradish peroxidase (HRP) molecules. 3,3'-Diaminobenzidine (DAB) will be used as a substrate for this enzyme to highlight the specific expression of the biomarker. The use of an automated system will ensure the reproducibility of inter-sample labelling.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes	Institut du Cancer de Montpellier - Val d'Aurelle

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Age	Age will be recorded in years	Baseline
Other	Weight	Weight will be recorded in kilograms	Baseline
Other	Height	Height will be recorded in centimeters	Baseline
Other	Radiotherapy protocol	The patient's radiotherapy protocol will be recorded	Baseline
Other	Chemotherapy	Details of the patient's chemotherapy will be recorded (drugs and dosage)	Baseline
Other	Brachytherapy	Details of the patient's brachytherapy will be recorded (type of internal radiation and dosage)	Baseline
Other	Anatomopathology of cervical cancer: histology	The histology of the patient's cervical cancer will be recorded	Baseline
Other	Anatomopathology of cervical cancer: FIGO stage	The FIGO stage of the patient's cervical cancer will be recorded. FIGO staging ranges from Stage I= Confined to the uterine corpus and ovary to Stage IIB=Substantial lymphovascular space involvement of non-aggressive histological types.	Baseline
Other	Family and personal history	The patient's family and personal history will be recorded	Baseline
Other	Co-medications	Any other concommitant treatment will be recorded	Baseline
Other	Initial clinical features	The initial clinical features of the disease will be recorded	Baseline
Other	Lifestyle	The patient's lifestyle (marital status, children, hobbies, professional status) will be recorded	Baseline
Other	Follow-up	All details of follow-up of the patient's oncological pathology (response rate, date of progression, date of death) will be recorded.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Other	Treatments received after progression	Details of all treatments received after disease progression will be recorded	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Primary	Prognostic role of overexpression of XIAP on the rate of local recurrence in patients treated for locally advanced cervical cancer.	Overexpression of the Inhibitor of Apoptosis Proteins XIAP will be measured to evaluate its prognostic role on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer. The H-score for XIAP will be recorded on a scale of 0 to 300 based on the intensity of carcinoma cells.	Baseline
Primary	Prognostic role of overexpression of XIAP on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer.	Overexpression of the Inhibitor of Apoptosis Proteins XIAP will be measured to evaluate its prognostic role on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer. The H-score for XIAP will be recorded on a scale of 0 to 300 based on the intensity of carcinoma cells.	24 months
Primary	Prognostic role of overexpression of cIAP1 on the rate of local recurrence in patients treated for locally advanced cervical cancer.	Overexpression of Inhibitors of the Apoptosis Protein cIAP1 will be measured to evaluate its prognostic role on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer.The H-score for cIAP1 be recorded on a scale of 0 to 300 based on the intensity of carcinoma cells.	Baseline
Primary	Prognostic role of overexpression of cIAP1 on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer.	Overexpression of the Inhibitor of Apoptosis Protein cIAP1 will be measured to evaluate its prognostic role on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer.The H-score for cIAP1 be recorded on a scale of 0 to 300 based on the intensity of carcinoma cells.	24 months
Primary	Prognostic role of overexpression of cIAP2 on the rate of local recurrence in patients treated for locally advanced cervical cancer.	Overexpression of the Inhibitor of Apoptosis Protein cIAP2 will be measured to evaluate its prognostic role on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer.The H-score for cIAP2 be recorded on a scale of 0 to 300 based on the intensity of carcinoma cells.	Baseline
Primary	Prognostic role of overexpression of cIAP2 on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer.	Overexpression of the Inhibitor of Apoptosis Protein cIAP2 will be measured to evaluate its prognostic role on the rate of local recurrence at 24 months follow-up in patients treated for locally advanced cervical cancer. The H-score for cIAP1 be recorded on a scale of 0 to 300 based on the intensity of carcinoma cells.	24 months
Primary	Local recurrence of cervical cancer	Local recurrence of cervical cancer at 24 months follow-up according to RECIST v1.1 criteria: Yes/No.; RECIST 1.1 is a standard way to measure the response of a tumor to treatment in which Complete Response = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. Partial Response = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Overall survival at 24 months follow-up in patients treated for locally advanced cervical cancer.
Secondary	A. Overall survival in patients treated for locally advanced cervical cancer at baseline.	Death will be recorded as YES/NO	Baseline
Secondary	A. Overall survival at 24 months follow-up in patients treated for locally advanced cervical cancer.	Death will be recorded as YES/NO	24 months
Secondary	B. Progression-free survival in patients treated for locally advanced cervical cancer.	The time from diagnosis to death from any cause will be recorded in months and days.	Baseline
Secondary	B. Progression-free survival at 24 months follow-up in patients treated for locally advanced cervical cancer.	The time from diagnosis to death from any cause will be recorded in months and days.	24 months
Secondary	B. Progression-free survival in patients treated for locally advanced cervical cancer: RECIST criteria	The time between diagnosis and progression according to v1.1 of the RECIST criteria or death from any cause will be recorded in days.; RECIST 1.1 is a standard way to measure the response of a tumor to treatment in which Complete Response = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. Partial Response = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Baseline
Secondary	B. Progression-free survival at 24 months follow-up in patients treated for locally advanced cervical cancer: RECIST criteria	The time between diagnosis and progression according to v1.1 of the RECIST criteria or death from any cause will be recorded in days.; RECIST 1.1 is a standard way to measure the response of a tumor to treatment in which Complete Response = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. Partial Response = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	24 months
Secondary	B. Progression-free survival in patients treated for locally advanced cervical cancer. H-score	The histochemical scoring assessment (H-SCORE) will be recorded on a scale of 0-300	Baseline
Secondary	B. Progression-free survival at 24 months follow-up in patients treated for locally advanced cervical cancer: H-score	The histochemical scoring assessment (H-SCORE) will be recorded on a scale of 0-300	24 months
Secondary	C. Correlation between the Inhibitor of Apoptosis Protein XIAP expression and Programmed Death - Ligand 1 expression.	The expression level of XIAP and the expression level of PD-L1 in biopsies will be measured by immunohistochemistry.	Baseline
Secondary	C. Correlation between the Inhibitor of Apoptosis Protein cIAP1 expression and Programmed Death - Ligand 1 expression.	The expression level of cIAP1 and the expression level of PD-L1 in biopsies will be measured by immunohistochemistry.	Baseline
Secondary	C. Correlation between the Inhibitor of Apoptosis Protein cIAP2 expression and Programmed Death - Ligand 1 expression.	The expression levels of cIAP2 and expression level of PD-L1 in biopsies will be measured by immunohistochemistry.	Baseline
Secondary	D. Correlation between the Inhibitor of Apoptosis Protein XIAP expression and lymphocytic tumour infiltration (LTI).	The expression level of XIAP and the level of lymphocytic tumour infiltration will be measured as % in biopsies.	Baseline
Secondary	D. Correlation between the Inhibitor of Apoptosis Protein cIAP1 expression and lymphocytic tumour infiltration (LTI).	The expression level of cIAP1 and the level of lymphocytic tumour infiltration will be measured as % in biopsies.	Baseline
Secondary	D. Correlation between the Inhibitor of Apoptosis Protein cIAP2 expression and lymphocytic tumour infiltration (LTI).	The expression level of cIAP2 and the level of lymphocytic tumour infiltration will be measured as % in biopsies.	Baseline