GYNO-MIR: Exploring the Potential of Novel Biomarkers Based on Plasma microRNAs for a Better Management of Pelvic Gynecologic Tumors

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03776630

Collaborator

Institut National de la Santé Et de la Recherche Médicale, France (Other)

363

Enrollment

Location

Arms

95.3

Anticipated Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial is a non-randomized, open label and multicenter study.

It aims to :

for endometrial cancer.:validate the 5-miR index assessed in plasma samples as a diagnostic marker to assess the risk of lymph node metastases for ovarian cancer : to validate the previous finding on the prognostic value of the pre-/post-treatment variation of miR200b plasma concentrations with regards to PFS (the investigators mean the primary treatment including up-front or post-chemotherapy debulking and adjuvant chemotherapy).

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer Endometrial Cancer	Other: Blood sample	N/A

Detailed Description

MicroRNAs (miRs) have been linked to carcinogenesis and can act as metastatic activators or suppressors. There is now ample evidence that circulating miRs can be used as biomarkers. This project is focused on ovarian (OC) and endometrial cancers (EC), respectively the deadliest and most frequent gynecologic malignancies.

The main challenge for physicians managing women with early-stage EC is when to opt for lymphadenectomy. Tools that are currently used are not accurate enough to identify women with increased risk of nodal metastases. Ballester's team recently found a relationship between the high expression of a set of 5 miRs in the primary tumor and nodal status.

OC is the leading cause of death from gynecological cancer. The prognosis depends on the response of the residual tumor mass to adjuvant chemotherapy. Currently, this response remains largely unpredictable and even difficult to monitor with CA125 measurements and current imaging techniques. Busson's team recently showed that the variation of plasma miR200b during primary treatment is predictive of progression-free survival (PFS).

The study involves 3 populations of participants :

Patients with EC
Patients with OC
Patients undergoing surgery for benign pelvic lesions (control population)

Study Design

Study Type:

Interventional

Actual Enrollment :

363 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Exploring the Potential of Novel Biomarkers Based on Plasma microRNAs for a Better Management of Pelvic Gynecologic Tumors

Actual Study Start Date :

May 23, 2019

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

May 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Other: Control Patients undergoing surgery for benign pelvic lesions	Other: Blood sample Two blood samples (2 tubes of 4 ml for each blood sample) will be collected per patient during the study period for EC and OC. One blood sample will be collected for control population. The first sample will be collected prior to any treatment for EC, OC, and control population. For EC, the second collection will be done one month post-surgery. For OC, the second collection will be done 6 to 9 months after the initial diagnosis, in most cases at the completion of adjuvant chemotherapy. For control population, there will be no second sample.
Other: Ovarian Cancer	Other: Blood sample Two blood samples (2 tubes of 4 ml for each blood sample) will be collected per patient during the study period for EC and OC. One blood sample will be collected for control population. The first sample will be collected prior to any treatment for EC, OC, and control population. For EC, the second collection will be done one month post-surgery. For OC, the second collection will be done 6 to 9 months after the initial diagnosis, in most cases at the completion of adjuvant chemotherapy. For control population, there will be no second sample.
Other: Endometrial Cancer	Other: Blood sample Two blood samples (2 tubes of 4 ml for each blood sample) will be collected per patient during the study period for EC and OC. One blood sample will be collected for control population. The first sample will be collected prior to any treatment for EC, OC, and control population. For EC, the second collection will be done one month post-surgery. For OC, the second collection will be done 6 to 9 months after the initial diagnosis, in most cases at the completion of adjuvant chemotherapy. For control population, there will be no second sample.

Arm

Intervention/Treatment

Other: Control

Patients undergoing surgery for benign pelvic lesions

Other: Blood sample

Two blood samples (2 tubes of 4 ml for each blood sample) will be collected per patient during the study period for EC and OC. One blood sample will be collected for control population. The first sample will be collected prior to any treatment for EC, OC, and control population. For EC, the second collection will be done one month post-surgery. For OC, the second collection will be done 6 to 9 months after the initial diagnosis, in most cases at the completion of adjuvant chemotherapy. For control population, there will be no second sample.

Other: Ovarian Cancer

Other: Blood sample

Other: Endometrial Cancer

Other: Blood sample

Outcome Measures

Primary Outcome Measures

For EC: presence or absence of lymph-node metastases according to pathological analysis (reference technique). [2 months]
To validate the 5-miR index assessed in plasma samples as a diagnostic marker to assess the risk of lymph node metastases.
For OC: PFS or death for any cause at 24 months. [24 months]
To validate the previous finding on the prognostic value of the pre-/post-treatment variation of miR200b plasma concentrations with regards to PFS (by OC treatment, we mean the primary treatment including up-front or post-chemotherapy debulking and adjuvant chemotherapy).

Secondary Outcome Measures

It aims to investigate the links of the 5-miR index with classical predictors of lymph node involvement in the context of EC. [2 months]
Histopathological characteristics of the tumor in the context of EC: grade
It aims to investigate the links of the 5-miR index with classical predictors of lymph node involvement in the context of EC (1) [2 months]
Histopathological characteristics of the tumor in the context of EC: type endometrioid vs. non endometrioid
It aims to assess the prognostic value of pre/post-operative plasma miR variations in terms of PFS in EC and OC [60 months]
PFS for both EC and OC
It aims to assess the prognostic value of pre/post-operative plasma miR variations in terms of OS in EC and OC [60 months]
OS (defined as the time from the start of the treatment to death) for both EC and OC
Sensitivity and specificity of plasma miR detection by RCA-FRET applied directly on plasma samples or following RNA extraction. [60 months]
it aims to validate multiplexed homogenous miR detection based on RCA-FRET compared to conventional qRT-PCR in plasma samples. It also aims to search for novel plasma miRs potentially informative on lymph node involvement (EC) or PFS (OC) by high throughput sequencing (RNA seq).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

For all patients (EC, OC, Control)

Written informed consent;
Age ≥ 18 years old;
Patient affiliated to social security.

EC patients

Histologically proven EC ;
Type 1 and 2 EC;
FIGO stage I or II or III EC requiring first intention surgical staging.

OC patients

Histologically proven OC or strong suspicion of OC on clinical arguments (abdomino-pelvian mass detected by palpation or echography and/or ascitis and/or elevated CA125);
Epithelial OC: any histological subtype;
FIGO stage I to IV OC.

Control patients - Any lesion which is supposed to be benign and requires surgery. -

Exclusion Criteria:

For all patients (OC, EC, Control)

Unable or unwilling to comply with the protocol requirements and/or unwilling to sign an informed consent form.
Deprived of liberty or under legal protection measure;
Ongoing pregnancy;

Control patients:

Previous history of cancer.

EC patients

FIGO stage IV at preoperative imaging techniques.
Previous history of cancer. OC patients
Non epithelial cancer.
Previous history of cancer - except for patients who developed breast cancer at least 5 years or more before ovarian cancer.