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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cancer of Cervix; Apoptosis
• Intervention / Treatment: Diagnostic test: Immunohistochemistry

Detailed 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.

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Anissa MEGZARI; Phone Number: +33466684236; Email: drc@chu-nimes.fr
• Study Contact Backup: Name: Frédéric FITENI, Dr.; Phone Number: +334.34.03.46.69; Email: frederic.fiteni@chu-nimes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

The study population is made up of women treated with the exclusive radio-chemotherapy combination for locally advanced cervical carcinoma, managed at the Montpellier Institute of Cancer and Montpellier and Nîmes University Hospitals.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
A. Overall survival in patients treated for locally advanced cervical cancer at baseline.	Death will be recorded as YES/NO	Baseline
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
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
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
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
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
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
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
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
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
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age	Age will be recorded in years	Baseline
Weight	Weight will be recorded in kilograms	Baseline
Height	Height will be recorded in centimeters	Baseline
Radiotherapy protocol	The patient's radiotherapy protocol will be recorded	Baseline
Chemotherapy	Details of the patient's chemotherapy will be recorded (drugs and dosage)	Baseline
Brachytherapy	Details of the patient's brachytherapy will be recorded (type of internal radiation and dosage)	Baseline
Anatomopathology of cervical cancer: histology	The histology of the patient's cervical cancer will be recorded	Baseline
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
Family and personal history	The patient's family and personal history will be recorded	Baseline
Co-medications	Any other concommitant treatment will be recorded	Baseline
Initial clinical features	The initial clinical features of the disease will be recorded	Baseline
Lifestyle	The patient's lifestyle (marital status, children, hobbies, professional status) will be recorded	Baseline
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
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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Collaborators: Institut du Cancer de Montpellier - Val d'Aurelle
• Investigators: Principal Investigator: Alexandre TAYART de BORMS, Interne, Nimes University Hospital; Principal Investigator: Cristina LEAHA, Dr., Institut Régional du Cancer de Montpellier, Service d'Anatomopathologie

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: November 13, 2023
• First Submitted That Met QC Criteria: November 17, 2023
• First Posted (Actual): November 28, 2023

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Cervical cancer; Apoptosis; Apoptosis inhibiting proteins
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Disease Attributes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms; Recurrence
• Other Study ID Numbers: NIMAO/2023-1/FF-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No