Prophylactic Irradiation of the Para-Aortic Lymph Nodes and Supraclavicular Lymph Nodes in Locally Advanced Uterine Cervical Cancer

Study Overview
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Brief Summary
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This study is an open-label, randomized study, which is designed to investigate the efficacy of Extended-field irradiation (EFI) on reducing recurrences at the para-aortic lymph node (PAN) and supraclavicular lymph nodes, and also on improving disease-free survival of locally advanced uterine cervical cancer. This study includes a translational research component in that all the primary tumors and lymph node are stained with Sema4c, before randomization. According to the investigators study result, patients with more pelvic lymph node metastasis are more likely to develop distant metastasis including the recurrences at PAN and supraclavicular lymph node. Primary cervical cancer tissues and lymph nodes are examined for expression of Sema4c just after registration, and before the patients are randomized to each arm (pelvis only vs. EFI). The investigators expect a higher benefit of EFI in patients with Sema4c-positive lymph node.

Official Title
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Molecular Markers in Lymph Node Metastasis of Cervical Cancer and Prophylactic Irradiation of the Para-Aortic Lymph Nodes and Supraclavicular Lymph Nodes in Locally Advanced Uterine Cervical Cancer

Conditions
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Cervical Cancer

Intervention / Treatment
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* Radiation: Prophylactic Irradiation of the Para-Aortic Lymph Nodes and supraclavicular lymph nodes in Locally Advanced Uterine Cervical Cancer
* Radiation: Prophylactic Irradiation of the Para-Aortic Lymph Nodes and supraclavicular lymph nodes in Locally Advanced Uterine Cervical Cancer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients (who have been adequately clinically staged) with primary, untreated, histologically confirmed invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, FIGO stage IB1 with pelvic lymph node metastasis, IB2, IIA(≥4cm in tumor size, or pelvic LN metastasis), IIB, IIIA, IIIB? with only unilateral pelvic wall extension Patients with negative, para-aortic lymphadenopathy determined by pelvic MRI and/or PET/CT scan. Patients with adequate bone marrow function: ANC greater than or equal to 1,500/ul, platelets greater than or equal to 100,000/ul at the beginning. Patients with adequate renal function: creatinine equal to or less than 2.0 mg/dL. Patients who have signed an approved informed consent and authorization Patients with ECOG Performance Status of 0, 1, 2 and Karnofsky Performance Scale of 100, 90, 80, 70, 60, 50 Age: 18≤age≤80 Exclusion Criteria: Stage IIIb with bilateral pelvic wall extension and stage IVB lesions are not eligible. Patients with histology other than squamous, adeno, adenosquamous cell carcinoma Patients who have received prior radiotherapy of pelvis or total hysterectomy Patients who have diagnosis of other malignant tumors other than non-malignant melanoma skin cancer or stage I. II papillary, follicular thyroid cancer.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| No Intervention: Sema4c positive +Common iliac lymph nodes control<br>Sema4c Positive & Radical hysterectomy +Pelvic Radiotherapy  | |
| Active Comparator: Sema4c positive +Common iliac lymph nodes Experimental<br>Sema4c Positive & Radical hysterectomy+ EFI(whole pelvis + para-aortic lymph node irradiation)  | Radiation: Prophylactic Irradiation of the Para-Aortic Lymph Nodes and supraclavicular lymph nodes in Locally Advanced Uterine Cervical Cancer<br>* Sema4c positive +Common iliac lymph nodes metastasis Experimental :Radical hysterectomy+ EFI(whole pelvis + para-aortic lymph node irradiation)<br>|
| No Intervention: Sema4c Positive + PAN positive control arm<br>Sema4c Positive &  Radical hysterectomy+ EFI(whole pelvis + para-aortic lymph node irradiation)  | |
| Experimental: Sema4c positive+ PAN positive Experimental<br>Sema4c Positive & Radical hysterectomy+ EFI(whole pelvis + para-aortic lymph node irradiation+ supraclavicular lymph nodes irradiation) ' | Radiation: Prophylactic Irradiation of the Para-Aortic Lymph Nodes and supraclavicular lymph nodes in Locally Advanced Uterine Cervical Cancer<br>* Sema4c positive+ Para-aortic lymph node metastasis Experimental : Radiation: Extended-field Irradiation (EFI) Prophylactic irradiation of supraclavicular lymph node<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of the Extended-Field Irradiation on the recurrence rate in para-aortic lymph nodes, supraclavicular lymph nodes and the disease-free survival rate of the patients with locally advanced uterine cervical cancer |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate overall survival, toxicities and quality of life (QOL) of the patients treated by EFI compared to the control group of patients |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical cancer,semaphorin 4C (Sema4C),, Prophylactic Irradiation