NCT05581121

Brief 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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
510

participants targeted

Target at P50-P75 for phase_3

Timeline
93mo left

Started Dec 2023

Longer than P75 for phase_3

Geographic Reach
4 countries

34 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress24%
Dec 2023Dec 2033

First Submitted

Initial submission to the registry

October 12, 2022

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 14, 2022

Completed
1.2 years until next milestone

Study Start

First participant enrolled

December 20, 2023

Completed
10 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 20, 2033

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 20, 2033

Last Updated

April 17, 2026

Status Verified

April 1, 2026

Enrollment Period

10 years

First QC Date

October 12, 2022

Last Update Submit

April 16, 2026

Conditions

Cervical CarcinomaAdenocarcinomaAdenosquamous Carcinoma

Keywords

Locally advanced cervical cancerHPV 16+Stage IIIC1Radiation therapyCisplatinPara-aortic lymphadenectomyINTERLACEKEYNOTE-A18

Outcome Measures

Primary Outcomes (1)

  • Disease Free Survival (DFS)

    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 Outcomes (8)

  • Overall survival (OS)

    5 years for each patient

  • Cancer Specific survival (CSS)

    5 years for each patient

  • Metastasis Free Survival (MFS)

    5 years for each patient

  • Para-aortic Free Survival (PAFS)

    5 years for each patient

  • Morbidity and adverse events assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v 5.0).

    5 years for each patient

  • +3 more secondary outcomes

Study Arms (2)

Arm A

OTHER

Control arm

Other: Standard treatment: Control arm

Arm B

EXPERIMENTAL

Experimental arm

Procedure: Experimental arm

Interventions

Experimental armPROCEDURE

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.

Arm B
Standard treatment: Control armOTHER

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

Arm A

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18 years at time of study entry
  • Newly diagnosed histologically proven cervical squamous carcinoma, adenocarcinoma, or adenosquamous tumor
  • 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).
  • Patients with TNM T stage I-IIIB.
  • 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)
  • Patient eligible for pelvic radiotherapy and cisplatin-based chemotherapy with a curative intent as confirmed by a multidisciplinary board
  • ECOG performance status \< 2 i.e. 0 or 1
  • Life expectancy more than 12 months
  • Pretherapeutic imaging FDG-PET/CT images should be available for central review
  • Prior validation of the surgeon's participation in the study by the Quality Assurance Comity
  • 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.
  • 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
  • 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
  • Signed informed consent
  • Patient affiliated to a Social Health Insurance in France (French patients only).

You may not qualify if:

  • Unequivocal positive common iliac or para-aortic lymph nodes at pretherapeutic imaging FDG-PET/CT
  • Negative or equivocal pelvic lymph nodes at pretherapeutic imaging FDG-PET/CT
  • Metastatic disease confirmed by FDG-PET/CT
  • Other histologies than adenocarcinoma, squamous cell carcinoma and adenosquamous carcinoma
  • Contraindication for cisplatin-based chemotherapy
  • Women who received any prior treatment for cervical cancer
  • Prior surgery for the cervical cancer, except for cone procedure and pelvic lymph node staging
  • Previous pelvic radiotherapy
  • 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.
  • 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
  • Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (34)

UH Plzeň

Pilsen, 326 00, Czechia

RECRUITING

General UH in Prague - VFN

Prague, 128 08, Czechia

RECRUITING

Institut de Cancérologie de l'Ouest

Angers, France

RECRUITING

Institut Bergonié

Bordeaux, France

RECRUITING

CHU Brest

Brest, France

RECRUITING

Centre François Baclesse

Caen, 14076, France

NOT YET RECRUITING

Centre Hospitalier Intercommunal de Créteil

Créteil, France

RECRUITING

Centre Georges François Leclerc

Dijon, France

RECRUITING

Centre Oscar Lambret

Lille, France

RECRUITING

CHRU Lille

Lille, France

RECRUITING

CHU Limoges

Limoges, France

RECRUITING

Centre Léon Bérard

Lyon, France

RECRUITING

Institut Paoli Calmettes

Marseille, France

RECRUITING

ICM Val d'Aurelle

Montpellier, France

RECRUITING

CHU Nîmes

Nîmes, France

RECRUITING

Hôpital Cochin

Paris, France

RECRUITING

Hôpital Européen Georges Pompidou

Paris, France

RECRUITING

Hôpital Lariboisière Saint Louis

Paris, France

RECRUITING

Hôpital Pitié-Salpêtrière

Paris, France

RECRUITING

Institut Curie

Paris, France

RECRUITING

Hôpital Lyon Sud

Pierre-Bénite, France

RECRUITING

Institut Godinot

Reims, 51726, France

NOT YET RECRUITING

Centre Henri Becquerel

Rouen, France

WITHDRAWN

Institut Curie Site - Saint Cloud

Saint-Cloud, 92210, France

NOT YET RECRUITING

Institut de Cancérologie de l'Ouest

Saint-Herblain, France

RECRUITING

Centre Hospitalier Universitaire La Reunion

Saint-Pierre, 97448, France

RECRUITING

CHRU Strasbourg - ICANS

Strasbourg, France

NOT YET RECRUITING

Institut Universitaire du Cancer Toulouse - Oncopole

Toulouse, 31059, France

RECRUITING

Chru Tours

Tours, France

RECRUITING

Institut Gustave Roussy

Villejuif, France

RECRUITING

Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

NOT YET RECRUITING

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

NOT YET RECRUITING

H. Clínico San Carlos / Madrid

Madrid, 28040, Spain

NOT YET RECRUITING

H.U. La Paz / Madrid

Madrid, 28046, Spain

RECRUITING

Related Publications (1)

  • Martinez A, Lecuru F, Bizzarri N, Chargari C, Ducassou A, Fagotti A, Fanfani F, Scambia G, Cibula D, Diaz-Feijoo B, Gil Moreno A, Angeles MA, Muallem MZ, Kohler C, Luyckx M, Kridelka F, Rychlik A, Gerestein KG, Heinzelmann V, Ramirez PT, Frumovitz M, Ferron G, Betrian S, Filleron T, Fotopoulou C, Querleu D; PAROLA Study group. PARa-aOrtic LymphAdenectomy in locally advanced cervical cancer (PAROLA trial): a GINECO, ENGOT, and GCIG study. Int J Gynecol Cancer. 2023 Feb 6;33(2):293-298. doi: 10.1136/ijgc-2022-004223.

    PMID: 36717163BACKGROUND

MeSH Terms

Conditions

Uterine Cervical NeoplasmsAdenocarcinomaCarcinoma, Adenosquamous

Condition Hierarchy (Ancestors)

Uterine NeoplasmsGenital Neoplasms, FemaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsUterine Cervical DiseasesUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasms, Complex and Mixed

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 12, 2022

First Posted

October 14, 2022

Study Start

December 20, 2023

Primary Completion (Estimated)

December 20, 2033

Study Completion (Estimated)

December 20, 2033

Last Updated

April 17, 2026

Record last verified: 2026-04

Locations

CZ(2)FR(28)ES(3)IT(1)