A Trial Comparing Observation With Radiation on Pelvic Lymphocysts After Radical Hysterectomy of Cervical Cancer

Study Overview
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Brief Summary
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Cervical cancer of early stage is treated mainly by radical resection and (or) radiotherapy. And pelvic lymphocyst is one of the most common adverse events of radical resection. The aim of this study is to compare observation with radiation on pelvic lymphocyst of cervical cancer patients after radical resection, for incidence of adverse events and local recurrence rate.

Detailed Description
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Background Cervical Cancer is one of the most common malignant tumors of Chinese females. The early stage diseases (Stage Ia, Ib and IIa1) is treated mainly by radical resection and (or) radiotherapy. And pelvic lymphocyst is one of the most common adverse events (incidence 18-35%) of radical resection. When adjuvant radiotherapy (ART) is performed, lymphocyst is included in the clinical target volume (CTV) with a dose of 45-50Gy, in most hospitals of China. However, there is no pathologic and clinical evidence that lymphocyst is associated with local recurrence. However, inclusion of lymphocyst might enlarge CTV and increase irradiation dose of organs at risk (OARs) such as small intestine and kidneys. Objective The aim of this study is to compare observation with radiation on pelvic lymphocyst of cervical cancer patients after radical resection, for incidence of adverse events and local recurrence rate. Patients and methods A patient will be enrolled when patient have: pathologically diagnosed cervical cancer; Stage I-II diseases (FIGO system ver. 2014); treated with radical resection; need of ART according to NCCN guidelines ver. 2016v2. Randomization is performed to divide the patients into the control group (Group A) and the experimental group (Group B). In Group A, the CTV includes all the lymphocyst. But in Group B, the CTV is delineated according to the lymph drainage pathway (not all the lymphocyst included). ART is performed with a dose of 60Gy to the gross tumor volume, and 45Gy to the CTV. Chemotherapy is given concurrently with cisplatin 30mg/m2 every week regimen. The Grade 3/4 adverse events (CTCAE criteria ver. 4.03) and the 5-year local-recurrence-free survival of the 2 groups are compared after 5-year follow-up with an interval of 3 months.

Official Title
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Observation Versus Radiation on Pelvic Lymphocysts After Radical Hysterectomy of Cervical Cancer: A Phase 3 Prospective Multi-institutional Randomised Controlled Trial

Conditions
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Cervical Cancer, Lymphocyst, Radiation Therapy

Intervention / Treatment
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* Radiation: Radiation Method B
* Drug: Cisplatin
* Radiation: Radiation Method A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with pathological diagnosed cervical cancer and treated with radical resection Stage I-II diseases (FIGO system ver. 2014) Karnofsky Performance Scores ≥ 80 and expected survival ≥ 3 months Pelvic MRI or CT indicate existence of lymphocyst Need of adjuvant radiotherapy according to NCCN guidelines ver. 2016v2 (SEDLIS criteria) Exclusion Criteria: Patients with distant metastasis before or during radiotherapy Severe dysfunction of heart, lung, liver, kidney or hematopoietic system Severe neurological, mental or endocrine diseases History of other malignancies Prior chemotherapy, radiotherapy or application of monoclonal antibodies Patients participated in clinical trials of other drugs within last 3 months Pregnant or lactating women Those who are considered by the researchers unsuitable to participate

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: The control group (Group A)<br>In Group A, adjuvant radio-chemotherapy is applied. The radiotherapy is performed according to Radiation Method A. The regimen of chemotherapy is cisplatin 30mg/m2 every week. | Drug: Cisplatin<br>* The regimen of chemotherapy is cisplatin 30mg/m2 every week.<br>Radiation: Radiation Method A<br>* The gross tumor volume (GTV) is the residual lesion after radical resection and given a dose of 60Gy. The clinical target volume (CTV) is delineated according to the lymph drainage pathway and given a dose of 45Gy.<br>|
| Experimental: The experiment group (Group B)<br>In Group B, adjuvant radio-chemotherapy is applied. The radiotherapy is performed according to Radiation Method B. The regimen of chemotherapy is cisplatin 30mg/m2 every week. | Radiation: Radiation Method B<br>* The gross tumor volume (GTV) is the residual lesion after radical resection and given a dose of 60Gy. The clinical target volume (CTV) is delineated according to the lymph drainage pathway and included all the lymphocyst. The CTV is given a dose of 45Gy.<br>Drug: Cisplatin<br>* The regimen of chemotherapy is cisplatin 30mg/m2 every week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-year local-recurrence-free survival (5y-LRFS) | Percentage of patients in a treatment group who are alive without local recurrence for a 5-year period of follow-up after the date of radiotherapy completion | 5 years after the date of radiotherapy completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of grade 3/4 adverse event | Incidence of patients in a treatment group who manifest a specific adverse event (such as myelosuppression) of grade 3/4. Incidence is calculated for each adverse event respectively and severity is evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) criteria ver. 4.03. | Once a week during therapy, up to 5 years after the date of radiotherapy completion | 
| 5-year overall survival (5y-OS) | Percentage of patients in a treatment group who are alive for a 5-year period of follow-up after the date of radiotherapy completion | 5 years after the date of radiotherapy completion |