A Trial Comparing Adjuvant Chemotherapy With Observation After Concurrent Chemoradiotherapy of Cervical Cancer (With Pelvic or Para-aortic Node Involvement)

Study Overview
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Brief Summary
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Cervical cancer with pelvic or para-aortic node involvement has a poor prognosis. Despite low-quality data, the routine practice to treat these patients is radiation with concurrent cisplatin. The aim of this study is to compare systemic chemotherapy with observation after radiation with concurrent cisplatin of cervical cancer ( with pelvic or para-aortic node involvement) 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. Women with evidence of para-aortic node involvement have a poor prognosis with a five-year survival rate of approximately 40 percent. Despite low-quality data, the routine practice to treat these patients is radiation with concurrent cisplatin. It is not clear whether systemic chemotherapy delivered following RT will obtain survival benefit. Objective The aim of this study is to compare systemic chemotherapy with observation after radiation with concurrent cisplatin of cervical cancer ( with pelvic or para-aortic node involvement) for incidence of adverse events, 3y-PFS and 5y-OS, . Patients A patient will be enrolled when patient have: Pathologically diagnosed cervical cancer; pelvic or para-aortic lymph metastases, at least match one of following CT or MRI scan shows pelvic or para-aortic node with a minimal axial diameter diameter ≥ 7mm in the largest plane pelvic or para-aortic lymph node shows necrosis or extra capsular spread PET/CT scan finds positive pelvic or para-aortic node lymph node biopsy confirms lymph metastase Stage IB1-IVA diseases (FIGO system ver. 2014) without treatment before; Karnofsky Performance Scores ≥ 70; 4.Method Randomization is performed to divide the patients into the control group (Group A) and the experimental group (Group B). In Group A, observation is given after radiation with concurrent cisplatin. But in Group B, three cycles of adjuvant chemotherapy ( Paclitaxel plus Cisplatin) are administered after radiation with concurrent cisplatin. The regimen of adjuvant chemotherapy following radiation is Paclitaxel 135mg/m2 plus Cisplatin 60mg/m2 once 3 weeks.The Grade 3/4 adverse events (CTCAE criteria ver. 4.03), the 3-year progression-free survival of the 2 groups, the 5-year overall survival of the 2 groups are compared. In Group A and Group B, both the radiation method and the regimen of concurrent chemotherapy are the same.The gross tumor volume (GTVnd) is the lymph node lesion and given a dose of 60Gy. The clinical target volume (CTV) is according to the lymph drainage pathway and given a dose of 45Gy. The regimen of concurrent chemotherapy is Cisplatin 80mg/m2 once three weeks.

Official Title
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Adjuvant Chemotherapy Versus Observation After Radiation With Concurrent Cisplatin of Cervical Cancer (With Pelvic or Para-aortic Node Involvement) :A Phase 3 Prospective Multi-institutional Randomised Controlled Trial

Conditions
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Cervical Cancer, Adjuvant Chemotherapy, Radiation, Lymph Node Metastases

Intervention / Treatment
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* Radiation: chemoradiation
* Drug: Paclitaxel, Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically diagnosed cervical cancer; pelvic or para-aortic lymph metastases, at least match one of following CT or MRI scan shows pelvic or para-aortic node with a minimal axial diameter diameter ≥ 7mm in the largest plane pelvic or para-aortic lymph node shows necrosis or extra capsular spread PET/CT scan finds positive pelvic or para-aortic node lymph node biopsy confirms lymph metastase Stage IB1-IVA diseases (FIGO system ver. 2014) without treatment before; Karnofsky Performance Scores ≥ 70; 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 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, observation is given after chemoradiation | Radiation: chemoradiation<br>* radiation with concurrent ciplatin<br>|
| Experimental: The experiment group (Group B)<br>in Group B, three cycles of Paclitaxel, Cisplatin are administered after radiation with concurrent cisplatin. The regimen of additional adjuvant chemotherapy following radiation is Paclitaxel 135mg/m2 plus Cisplatin 60mg/m2 once 3 weeks. | Radiation: chemoradiation<br>* radiation with concurrent ciplatin<br>Drug: Paclitaxel, Cisplatin<br>* The regimen of additional adjuvant chemotherapy following radiation is Paclitaxel, Cisplatin once 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year progression-free survival (3y-PFS) | Percentage of patients in a treatment group who are alive without disease get worse for a 3-year period of follow-up after the date of adjuvant chemotherapy completion | 3 years after the date of adjuvant chemotherapy 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 adjuvant chemotherapy completion |