PARa-aOrtic LymphAdenectomy in Locally Advanced Cervical Cancer

Summary

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.

Conditions

• Cervical Carcinoma
• Adenocarcinoma
• Adenosquamous Carcinoma

Interventions

OTHER

Standard treatment: Control arm

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

PROCEDURE

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.

Sponsors & Collaborators

• ARCAGY/ GINECO GROUP

  collaborator OTHER

• European Network of Gynaecological Oncological Trial Groups (ENGOT)

  collaborator OTHER

• Gynecologic Cancer Intergroup (GCIG)

  collaborator OTHER

• Grupo Español de Investigación en Cáncer de Ovario

  collaborator OTHER

• Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies

  collaborator UNKNOWN

• Belgian Gynaecological Oncology Group

  collaborator OTHER

• Swiss GO Trial Group

  collaborator NETWORK

• Institute of Cancer Research, United Kingdom

  collaborator OTHER

• The Central and Eastern European Gynecologic Oncology Group

  collaborator OTHER

• Hellenic Cooperative Oncology Group

  collaborator OTHER

• Institut Claudius Regaud

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-12-20

Primary Completion

2033-12-20

Completion

2033-12-20

Countries

• Czechia
• France
• Italy
• Spain

Study Locations