PARa-aOrtic LymphAdenectomy in Locally Advanced Cervical Cancer

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

510 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-20

Study Completion Date

2033-12-31

Brief Summary

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This is an international, multicenter and randomized open-label phase III study designed to demonstrate, in patients with stage IIIC1 cervical cancer, whether para-aortic lymphadenectomy followed by tailored chemoradiation is associated with increased disease-free survival compared to patients staged with FDG-PET/CT only followed by chemoradiation.

The planned sample size is 510; including 200 patients in France.

In this trial, patients will be assigned in one of the two following treatments arms:

* Arm A (control arm): Standard chemo-radiotherapy and brachytherapy according to EMBRACE II and ESGO/ESTRO recommendations.
* Arm B (experimental arm): Pretherapeutic para-aortic lymphadenectomy followed by tailored chemo-radiotherapy and brachytherapy.

Considering the changing standard treatment landscape of locally advanced cervical cancer, both arms (control arm and experimental arm) may also be treated according to the INTERLACE and KEYNOTE-A18 studies, if applicable, at the discretion of the attending physician.

Each patient will be followed up for 5 years.

A cost-utility study will be performed in patients included in France. Other countries could be involved in this specific study. It will assess the incremental cost-utility ratio (cost per QALY gained) of para-aortic lymphadenectomy followed by tailored chemo-radiation in patients with positive PALN compared to patients staged with PET/CT only followed by chemo-radiation.

This study also has ancillary objectives:

* Biologic: To study T cell exhaustion, immune changes during chemoradiation, HPV ctDNA dynamic evolution, and the par-aortic lymph node as a premetastatic niche.
* Radiomics: To study the contribution of radiomics and FDG-PET/CT metabolic parameters to predict para-aortic lymph node involvement and clinical outcome.
* Senti-PAROLA: To evaluate the accuracy (Sensitivity, specificity, positive and negative predictive value) of the para-aortic sentinel lymph node (SPA) for PALN staging, and to evaluate the prognostic value of low volume metastasis of SPA.

Detailed Description

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Conditions

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Cervical Carcinoma Adenocarcinoma Adenosquamous Carcinoma

Keywords

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Locally advanced cervical cancer HPV 16+ Stage IIIC1 Radiation therapy Cisplatin Para-aortic lymphadenectomy INTERLACE KEYNOTE-A18

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A

Control arm

Group Type OTHER

Standard treatment: Control arm

Intervention Type OTHER

Standard chemo-radiotherapy and brachytherapy according to EMBRACE II and ESGO/ESTRO recommendations.

Arm B

Experimental arm

Group Type EXPERIMENTAL

Experimental arm

Intervention Type PROCEDURE

Pre-therapeutic para-aortic lymphadenectomy (by minimally invasive approach) followed by tailored chemo-radiotherapy and brachytherapy. Both traditional laparoscopy or robotically assisted laparoscopy approaches are accepted in the study.

Interventions

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Standard treatment: Control arm

Standard chemo-radiotherapy and brachytherapy according to EMBRACE II and ESGO/ESTRO recommendations.

Intervention Type OTHER

Experimental arm

Pre-therapeutic para-aortic lymphadenectomy (by minimally invasive approach) followed by tailored chemo-radiotherapy and brachytherapy. Both traditional laparoscopy or robotically assisted laparoscopy approaches are accepted in the study.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Age ≥ 18 years at time of study entry
2. Newly diagnosed histologically proven cervical squamous carcinoma, adenocarcinoma, or adenosquamous tumor
3. FIGO stage IIIC1 (FIGO 2018) cervical cancer with FDG-PET/CT showing FDG-positive pelvic nodes and FDG-negative PALN including equivocal lymph nodes in the common iliac and para-aortic regions. The highest positive lymph node must be located inferior to the common iliac bifurcation in both sides (anatomical level 1).
4. Patients with TNM T stage I-IIIB.
5. FIGO stage IIIC1 cervical cancer by positive pelvic sentinel lymph node from surgical staging (either intraoperative assessment (frozen section) or from final histology - patients are not eligible after radical hysterectomy, and FDG-negative common iliac of para-aortic lymph node on PET/CT (performed before or after SLN procedure)
6. Patient eligible for pelvic radiotherapy and cisplatin-based chemotherapy with a curative intent as confirmed by a multidisciplinary board
7. ECOG performance status \< 2 i.e. 0 or 1
8. Life expectancy more than 12 months
9. Pretherapeutic imaging FDG-PET/CT images should be available for central review
10. Prior validation of the surgeon's participation in the study by the Quality Assurance Comity
11. Women should be post-menopaused or willing to accept the use of an effective contraceptive regimen during the treatment period. All non-menopaused women should have a negative pregnancy test within 72 hours prior to study entry.
12. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
13. Not applicable since protocol revision V4. Patient participating to other clinical trials including immunotherapy strategies or adjuvant chemotherapy is also eligible for the study. Adjuvant treatment must be decided prior to randomization
14. Signed informed consent
15. Patient affiliated to a Social Health Insurance in France (French patients only).

Exclusion Criteria

1. Unequivocal positive common iliac or para-aortic lymph nodes at pretherapeutic imaging FDG-PET/CT
2. Negative or equivocal pelvic lymph nodes at pretherapeutic imaging FDG-PET/CT
3. Metastatic disease confirmed by FDG-PET/CT
4. Other histologies than adenocarcinoma, squamous cell carcinoma and adenosquamous carcinoma
5. Contraindication for cisplatin-based chemotherapy
6. Women who received any prior treatment for cervical cancer
7. Prior surgery for the cervical cancer, except for cone procedure and pelvic lymph node staging
8. Previous pelvic radiotherapy
9. History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease after 5 years, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, adequately treated carcinoma in situ (any location) without evidence of disease.
10. Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure
11. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice).

Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Reference Type DERIVED

PMID: 36717163 (View on PubMed)

Other Identifiers

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22GENF08

Identifier Type: -

Identifier Source: org_study_id

PARa-aOrtic LymphAdenectomy in Locally Advanced Cervical Cancer

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Study Groups

Arm A

Standard treatment: Control arm

Arm B

Experimental arm

Interventions

Standard treatment: Control arm

Experimental arm

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

ARCAGY/ GINECO GROUP

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Gynecologic Cancer Intergroup (GCIG)

Grupo Español de Investigación en Cáncer de Ovario

Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies

Belgian Gynaecological Oncology Group

Swiss GO Trial Group

Institute of Cancer Research, United Kingdom

The Central and Eastern European Gynecologic Oncology Group

Hellenic Cooperative Oncology Group

Institut Claudius Regaud

Responsible Party

Locations

Institut de Cancérologie de l'Ouest

Institut Bergonié

CHU Brest

Centre François Baclesse

Centre Hospitalier Intercommunal de Créteil

Centre Georges François Leclerc

Centre Oscar Lambret

CHRU Lille

CHU Limoges

Centre Léon Bérard

Institut Paoli Calmettes

ICM Val d'Aurelle

CHU Nîmes

Hôpital Cochin

Hôpital Européen Georges Pompidou

Hôpital Lariboisière Saint Louis

Hôpital Pitié-Salpêtrière

Institut Curie

Hôpital Lyon Sud

Institut Godinot

Centre Henri Becquerel

Institut Curie Site - Saint Cloud

Institut de Cancérologie de l'Ouest

Centre Hospitalier Universitaire La Reunion

CHRU Strasbourg - ICANS

Institut Universitaire du Cancer Toulouse - Oncopole

Chru Tours

Institut Gustave Roussy

Policlinico Universitario Agostino Gemelli

Hospital Clinic Barcelona

Countries

Facility Contacts

Noémie BODY

Guillaume BABIN

Pierre-François DUPRE

Léopold GAICHIES, MD

Jennifer UZAN

Hélène COSTAZ

Anne-Sophie NAVARRO

Yohan KERBAGE

Tristan GAUTHIER

Léa ROSSI

Guillaume BLACHE

Pierre-Emmanuel COLOMBO

Catherine FERRER

Bruno BORGHESE

Anne-Sophie BATS