PARa-aOrtic LymphAdenectomy in Locally Advanced Cervical Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 510
- 试验地点
- 62
- 主要终点
- Disease Free Survival (DFS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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 V
- •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).
排除标准
- •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).
研究组 & 干预措施
Arm A
Control arm
干预措施: Standard treatment: Control arm (Other)
Arm B
Experimental arm
干预措施: Experimental arm (Procedure)
结局指标
主要结局
Disease Free Survival (DFS)
时间窗: 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.
次要结局
- Cost-utility analysis(5 years for each patient)
- 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)
- Morbidity and adverse events assessed by the toxicity grading of the National Cancer Institute (NCI-CTCAE v 5.0).(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.(5 years for each patient)
- Para-aortic Free Survival (PAFS)(5 years for each patient)
- False-negative rate of PET/CT and optional ultrasonography(3 months post-CRT (Chemo-radiotherapy and brachytherapy) treatment for each patient)