PARa-aOrtic LymphAdenectomy in Locally Advanced Cervical Cancer
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexFemale
Age18+
SponsorInstitut Claudius Regaud
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Standard treatment: Control arm
Other interventionStandard chemo-radiotherapy and brachytherapy according to EMBRACE II and ESGO/ESTRO recommendations.
Experimental arm
Procedure/SurgeryPre-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.
Treatment groups
510 Participants
are divided into 2 treatment groupsGroup A: Arm AOther 1 intervention
Group B: Arm BExperimental treatment 1 intervention
Trial outcomes
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.
Time frame
5 years for each patientSecondary outcomes
1
Overall survival (OS)
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.
Time frame
5 years for each patient2
Cancer Specific survival (CSS)
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.
Time frame
5 years for each patient3
Metastasis Free Survival (MFS)
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.
Time frame
5 years for each patient4
Para-aortic Free Survival (PAFS)
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.
Time frame
5 years for each patientSponsors and contacts
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Institut Claudius Regaud
Lead sponsor
ARCAGY/ GINECO GROUP
Collaborator
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Collaborator
Gynecologic Cancer Intergroup (GCIG)
Collaborator
Grupo Español de Investigación en Cáncer de Ovario
Collaborator
Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies
Collaborator
Belgian Gynaecological Oncology Group
Collaborator
Swiss GO Trial Group
Collaborator
Institute of Cancer Research, United Kingdom
Collaborator
The Central and Eastern European Gynecologic Oncology Group
Collaborator
Hellenic Cooperative Oncology Group
Collaborator
Source ClinicalTrials.gov