Pelvic RT Versus Prophylactic Extended-field RT in Patients With Cervical Cancer

Study Overview
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Brief Summary
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To investigate the value of prophylactic extended-field irradiation (EFI), we conduct a randomized clinical trial to compare the efficacy and toxicity of pelvic irradiation and prophylactic EFI in selected patients with cervical cancer treated with definitive concurrent chemoradiotherapy. External beam radiation therapy is delivered with intensity-modulated radiation therapy (IMRT).

Detailed Description
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This is a multicenter, open-label, phase III randomized clinical trial. Cervical cancer patients without evidence of para-aortic metastatic lymph nodes (MLNs) and with at least one of the following characteristics are included in the present study: (a) Number of pelvic MLNs ≥ 2; (b)Short diameter of pelvic MLNs ≥ 1.5cm; (c)Pelvic wall involvement. Patients are randomly assigned to pelvic irradiation group and prophylactic EFI group. Patients in pelvic irradiation group receive pelvic irradiation, intracavitary brachytherapy and concurrent chemotherapy. Patients in prophylactic EFI group receive irradiation for pelvis and para-aortic lymph nodes region, intracavitary brachytherapy and concurrent chemotherapy. The upper border of clinical target volume (CTV) is at the level of renal vessels for patients in prophylactic EFI group. A dose of 45-50.4 Gy is delivered to CTV with IMRT in both groups. Patients receive cisplatin based concurrent chemotherapy (single cisplatin or cisplatin plus paclitaxel). The primary endpoint is progression-free survival.

Official Title
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Pelvic Irradiation Versus Prophylactic Extended-field Irradiation in Selected Patients With Cervical Cancer Treated With Concurrent Chemoradiotherapy: A Multicenter, Open-label, Randomized, Phase 3 Trial

Conditions
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Uterine Cervical Neoplasms

Intervention / Treatment
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* Radiation: Prophylactic extended-field Irradiation
* Radiation: Pelvic irradiation
* Radiation: Intracavitary brachytherapy
* Drug: Concurrent chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be informed of the investigational nature of this study and give written informed consent with 30 days before treatment. Age ≥18 years and ≤ 70 years. Patients with newly histologically confirmed cervical cancer, including squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma, et al. No evidence of para-aortic metastatic lymph nodes (MLNs) on CT, MRI or positron emission tomograph (PET)/CT.* No evidence of distant metastasis (FIGO stage IVB). At least meet one of the following characteristics: Number of pelvic MLNs ≥ 2; Short diameter of pelvic MLNs ≥ 1.5cm; * Parametrial involvement to the pelvic wall ＃. Satisfactory performance: Eastern Cooperative Oncology Group (ECOG) score ≥ 2. Adequate marrow: neutrophile granulocyte count ≥1.5*10^9/L, hemoglobin ≥ 80 g/L, platelet count ≥100*10^9/L. Normal liver and kidney function: Creatinine (Cr) < 1.5 mg/dl, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) < 2*upper limit of normal (ULN). MLNs refer to positive lymph nodes confirmed by PET/CT or lymph nodes with short diameter ≥ 1 cm on CT or MRI. Parametrial involvement to the pelvic wall is diagnosed with gynecological examination or MRI; Exclusion Criteria: With common iliac MLNs. Tumor extended to the lower third of the vagina. Tumor spread to mucosa of the bladder or rectum. Prior surgery (including pelvic or para-aortic lymph nodes resection, except for tumor biopsy), radiotherapy or chemotherapy to primary tumor or nodes. Prior malignancy. History of previous radiotherapy to the abdomen or pelvis. Pregnancy or lactation. Active inflammatory bowel disease, or history of severe stomach or duodenal ulcer. Active infection with fever. Patients with unacceptable risk that intracavitary brachytherapy can not be conducted. Any severe disease which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control, and emotional disturbance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pelvic Irradiation<br>Patients receive concurrent chemoradiotherapy. The CTV includes the gross tumor, cervix, uterus, parametrium, upper part of the vagina, and pelvic lymph nodes regions. The upper border of CTV is at the level of aortic bifurcation. A dose of 45-50.4Gy is delivered to CTV with IMRT. | Radiation: Pelvic irradiation<br>* CTV covers pelvis.<br>* Other names: Pelvic radiotherapy;Radiation: Intracavitary brachytherapy<br>* The total dose delivered to point A or high-risk CTV is ≥80Gy. For patients with larger-volume cervical tumor, the total dose is ≥85Gy.<br>* Other names: Brachytherapy;Drug: Concurrent chemotherapy<br>* Cisplatin based concurrent chemotherapy, including cisplatin as a single agent or cisplatin plus Paclitaxel.<br>* Other names: Chemotherapy;|
| Experimental: Prophylactic EFI<br>Patients receive concurrent chemoradiotherapy. The CTV includes the gross tumor, cervix, uterus, parametrium, upper part of the vagina, pelvic lymph nodes regions and para-aortic lymph nodes region. The upper border of CTV is at the level of renal vessels. A dose of 45-50.4Gy is delivered to CTV with IMRT. | Radiation: Prophylactic extended-field Irradiation<br>* CTV covers pelvis and para-aortic lymph nodes region.<br>* Other names: Prophylactic radiotherapy for para-aortic lymph nodes region;Radiation: Intracavitary brachytherapy<br>* The total dose delivered to point A or high-risk CTV is ≥80Gy. For patients with larger-volume cervical tumor, the total dose is ≥85Gy.<br>* Other names: Brachytherapy;Drug: Concurrent chemotherapy<br>* Cisplatin based concurrent chemotherapy, including cisplatin as a single agent or cisplatin plus Paclitaxel.<br>* Other names: Chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival is defined as the time from randomization to disease progression or death from any cause, whichever is first. | 3-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is calculated from randomization to death from any cause. | 3-year | 
| Distant failure-free survival | Distant failure-free survival is defined as the time from randomization to distant metastasis or death from any cause, whichever is first. | 3-year | 
| Para-aortic lymph nodes failure rate | The incidence of para-aortic lymph nodes failure. | 3-year | 
| Acute toxicity evaluated with CTCAE 5.0 | Evaluated with CTCAE 5.0 | From the start of treatment to 3 months after treatment. | 
| Late toxicity evaluated with Radiation Therapy Oncology Group (RTOG)/EORTC late radiation morbidity scoring scheme | Evaluated with Radiation Therapy Oncology Group (RTOG)/EORTC late radiation morbidity scoring scheme | 3-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uterine Cervical Neoplasms, Extended-field irradiation