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Clinical Trials in France / NCT05581121
Recruiting Phase 3

PARa-aOrtic LymphAdenectomy in Locally Advanced Cervical Cancer

NCT05581121 · tracked via the Priya Life Science France tracker
Phase
Phase 3
Started
2023-12-20
Last updated
2026-07-07

Condition(s) studied

Cervical CarcinomaAdenocarcinomaAdenosquamous Carcinoma

Investigational drug(s) / intervention(s)

Standard treatment: Control armExperimental arm

Standard treatment: Control arm: Standard chemo-radiotherapy and brachytherapy according to EMBRACE II and ESGO/ESTRO recommendations.

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.

Study 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.

Eligibility

Sex
FEMALE
Min age
18 Years
Max age
—
Healthy volunteers
No
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).

Primary outcome measure(s)

Trial sites (37)

FacilityCityRegionStatus
UH Ostrava - FNO Ostrava Czechia Recruiting
UH Plzeň Pilsen Czechia Recruiting
General UH in Prague - VFN Prague 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 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 France Not Yet Recruiting
Centre Henri Becquerel Rouen France Withdrawn
Institut Curie Site - Saint Cloud Saint-Cloud France Not Yet Recruiting
Institut de Cancérologie de l'Ouest Saint-Herblain France Recruiting
Centre Hospitalier Universitaire La Reunion Saint-Pierre France Recruiting
CHRU Strasbourg - ICANS Strasbourg France Not Yet Recruiting
Institut Universitaire du Cancer Toulouse - Oncopole Toulouse France Recruiting
Chru Tours Tours France Recruiting
Institut Gustave Roussy Villejuif France Recruiting
Policlinico Universitario Agostino Gemelli Roma Italy Not Yet Recruiting
H.U. Vall d'Hebron Barcelona Spain Recruiting
Hospital Clinic i Provincial de Barcelona Barcelona Spain Recruiting
H. Josep Trueta Girona Spain Recruiting
H. Clínico San Carlos / Madrid Madrid Spain Recruiting
H.U. La Paz / Madrid Madrid Spain Recruiting

More Institut Claudius Regaud trials in France

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05581121 on ClinicalTrials.gov ↗ ← All trials in France