PARa-aOrtic LymphAdenectomy in Locally Advanced Cervical Cancer (PAROLA)

May 21, 2026 updated by: Institut Claudius Regaud

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

510

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Czechia
      • Ostrava, Czechia, 708 52
        • Recruiting
        • UH Ostrava - FNO
        • Contact:
      • Pilsen, Czechia, 326 00
      • Prague, Czechia, 128 08
        • Recruiting
        • General UH in Prague - VFN
        • Contact:
  • France
      • Angers, France
      • Bordeaux, France
      • Brest, France
      • Caen, France, 14076
      • Créteil, France
        • Recruiting
        • Centre Hospitalier Intercommunal de Creteil
        • Contact:
      • Dijon, France
        • Recruiting
        • Centre Georges Francois Leclerc
        • Contact:
          • Hélène COSTAZ
          • Phone Number: +33 (0) 3 80 73 75 08
          • Email: hcostaz@cgfl.fr
      • Lille, France
        • Recruiting
        • Centre Oscar Lambret
        • Contact:
      • Lille, France
      • Limoges, France
      • Lyon, France
      • Marseille, France
      • Montpellier, France
      • Nîmes, France
      • Paris, France
        • Recruiting
        • Hôpital Européen Georges Pompidou
        • Contact:
      • Paris, France
        • Recruiting
        • Hopital Cochin
        • Contact:
      • Paris, France
        • Recruiting
        • Hôpital Pitié-Salpêtrière
        • Contact:
      • Paris, France
        • Recruiting
        • Institut Curie
        • Contact:
      • Paris, France
        • Recruiting
        • Hôpital Lariboisière Saint Louis
        • Contact:
      • Pierre-Bénite, France
      • Reims, France, 51726
      • Rouen, France
        • Withdrawn
        • Centre Henri Becquerel
      • Saint-Cloud, France, 92210
        • Not yet recruiting
        • Institut Curie Site - Saint Cloud
        • Contact:
      • Saint-Herblain, France
      • Saint-Pierre, France, 97448
        • Recruiting
        • Centre Hospitalier Universitaire La Reunion
        • Contact:
      • Strasbourg, France
      • Toulouse, France, 31059
      • Tours, France
      • Villejuif, France
  • Italy
      • Roma, Italy, 00168
  • Spain
      • Barcelona, Spain, 08036
        • Not yet recruiting
        • Hospital Clinic i Provincial de Barcelona
        • Contact:
      • Madrid, Spain, 28040
        • Not yet recruiting
        • H. Clínico San Carlos / Madrid
        • Contact:
      • Madrid, Spain, 28046

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Arm A
Control arm
Other: Standard treatment: Control arm
Standard chemo-radiotherapy and brachytherapy according to EMBRACE II and ESGO/ESTRO recommendations.
Experimental: Arm B
Experimental arm
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Free Survival (DFS)
Time Frame: 5 years for each patient
DFS is defined as the time from randomization until first relapse (local, regional, or distant), or death from any cause. Patients still alive at the time of analysis without documented event (including lost to follow-up) will be censored at the last valid disease assessment.
5 years for each patient

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: 5 years for each patient
OS is defined by the delay between randomization and death from any cause. Patients still alive at the time of analysis (including lost of follow-up) will be censored at the last known alive date.
5 years for each patient
Cancer Specific survival (CSS)
Time Frame: 5 years for each patient
CSS is defined by the delay between randomization and death from cancer. Patients still alive at the time of analysis (including lost of follow-up) or death from other cause will be censored at the last known alive date and date of death, respectively.
5 years for each patient
Metastasis Free Survival (MFS)
Time Frame: 5 years for each patient
MFS is defined as the time from randomization until first distant relapse, or death from any cause. Patients still alive at the time of analysis (including loss of follow-up) without appearance of distant relapse will be censored at the last valid disease assessment.
5 years for each patient
Para-aortic Free Survival (PAFS)
Time Frame: 5 years for each patient
PAFS is defined as the time from randomization until para-aortic recurrence, or death from any cause. Patients still alive at the time of analysis (including loss of follow-up) without appearance of para-aortic recurrence will be censored at the last valid disease assessment.
5 years for each patient
Morbidity and adverse events assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v 5.0).
Time Frame: 5 years for each patient
5 years for each patient
Quality of life will evaluated by the EORTC QLQ-C-30 questionnaire and its cervical cancer module (CXC-24) and the EQ-5D-5L questionnaire.
Time Frame: 5 years for each patient
The QLQ-C-30 response options are a 4-point Likert scale from "not at all" to "very much" or a seven-point Likert scale from "very poor" to "excellent."The QLQ-CX24 consists of 24 questions including symptom items and sexuality items. The scores/dimensions are: Body image, symptom experience, Sexual/Vaginal Functioning, Lymphedema, Peripheral Neuropathy, Menopausal Symptoms, Sexual Worry, Sexual Activity, sexual enjoyment.The EQ-5D-5L has a descriptive component (composed of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and a visual analogue scale (EQ-VAS). The EQ-5D-5L is translated and validated in French with a utility function calculated on the basis of revealed preferences of French population. The utility-preference approach of the EQ-5D-5L provides a scale with cardinal properties to calculate quality-adjusted life years (QALYs) that are uses in cost-utility analyses.
5 years for each patient
Cost-utility analysis
Time Frame: 5 years for each patient

Cost per QALYs gained at 3 year and 5-year follow-up:

  • QALYs gained estimated as the area between the quality-adjusted survival curves of both groups.
  • Utilities are derived from the EQ-5D-5L questionnaire using French weights.
5 years for each patient
False-negative rate of PET/CT and optional ultrasonography
Time Frame: 3 months post-CRT (Chemo-radiotherapy and brachytherapy) treatment for each patient
False-negative rate of PET/CT and optional ultrasonography for PALN (Para-Aortic Lymph Node) staging is defined as the ratio of the number of patients PALN+ on para-aortic lymphadenectomy (surgical staging) among the number of patients randomized in the experimental arm (in the overall population and in the subgroup of patients with equivocal lymph nodes).
3 months post-CRT (Chemo-radiotherapy and brachytherapy) treatment for each patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Claudius Regaud

Collaborators

Institute of Cancer Research, United Kingdom
Hellenic Cooperative Oncology Group
European Network of Gynaecological Oncological Trial Groups (ENGOT)
ARCAGY/ GINECO GROUP
Belgian Gynaecological Oncology Group
Grupo Español de Investigación en Cáncer de Ovario
Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies
Gynecologic Cancer Intergroup (GCIG)
Swiss GO Trial Group
The Central and Eastern European Gynecologic Oncology Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 20, 2023

Primary Completion (Estimated)

December 20, 2033

Study Completion (Estimated)

December 20, 2033

Study Registration Dates

First Submitted

October 12, 2022

First Submitted That Met QC Criteria

October 12, 2022

First Posted (Actual)

October 14, 2022

Study Record Updates

Last Update Posted (Actual)

May 26, 2026

Last Update Submitted That Met QC Criteria

May 21, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22GENF08

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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