Comparison of Different Subsequent Treatments After Radical Surgery

Study Overview
=================
Brief Summary
-----------------
Cervical cancer is still the most common gynecologic cancer. There was no obvious increase of the survival over years. The risk of recurrence after radical surgery has increased with positive lymph nodes, positive surgical margins, positive lymphatic vascular space and deep invasion of the cervical stroma. In recent years, the role of chemotherapy for cervical cancer has been gradually recognized. But as a adjuvant therapy post-surgery, if chemotherapy can improve the overall survival rate of patients with adverse pathological prognostic factors is inconclusive. In this study, in order to investigate the effect and adverse reaction of chemotherapy as the adjuvant therapy post-surgery on patients with adverse pathological prognostic factors, nine hundred and ninety patients will be randomly divided into three groups, comparing radiotherapy alone, concurrent chemoradiation and sequence chemotherapy and radiotherapy (2 cycles chemotherapy of Paclitaxel and Cisplatin before and after the irradiation). The investigators aim to find out the best therapeutic regimen with lowest adverse reaction for cervical cancer with adverse pathological prognostic factors. To guide clinical treatment options.

Detailed Description
-----------------
After radical surgery, patients with stage IB1 to IIA2 cervical cancer who had one or more following pathological factors were recruited: lymph node metastases (LNM), positive parametrium or margins (PPM), lymphatic vascular space involvement (LVSI), deep invasion of cervical stromal (DIS). Eligible patients were randomized to three groups. Group A underwent 50 GY RT alone. Group B received concurrent weekly cisplatin and RT. Group C received paclitaxel and bolus cisplatin every three weeks for two cycles before RT, followed by two cycles. We have recruited 800 patients till November 2014.

Official Title
-----------------
Comparison of Different Adjuvant Treatments Following Radical Surgery in Early Stage Cervical Carcinoma

Conditions
-----------------
Cervical Cancer

Intervention / Treatment
-----------------
* Radiation: Radiotherapy (RT)
* Other: Concurrent chemoirradiation (CCRT)
* Other: Sequence chemotherapy and radiotherapy (SCRT)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with newly histologically confirmed cervical carcinoma Original clinical stage must be Ib IIa （FIGO） Age between 18-65 With the presence of these four factors after radical surgery:(1)positive lymph nodes,(2)positive parametria, or positive surgical margins,(3)positive lymphatic vascular space,(4)outer one-third invasion of the cervical stroma More than 3 months survival is to expect Patients must give signed informed consent Exclusion Criteria: The presence of uncontrolled life-threatening illness Receiving other ways of anti-cancer therapy Residual tumor which can not be removed in the surgery Investigator consider the patients can't finish the whole study With normal liver function test (ALT、AST>2.5×ULN) With normal renal function test (Creatinine>1.5×ULN) WBC<4,000/mm3 or PLT<100,000/mm3 Receive the external pelvic irradiation before the surgery

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: After radical surgery, eligible patients with risk pathological factors were randomize to three groups. Radiotherapy: Group A underwent 50 GY pelvic RT alone. Radiotherapy and drugs: Group B received concurrent weekly cisplatin and RT (CCRT). Radiotherapy and drugs: Group C received paclitaxel and bolus cisplatin every three weeks for two cycles before RT, followed by two cycles of chemotherapy (SCRT).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Radiotherapy (RT)<br>Radiotherapy | Radiation: Radiotherapy (RT)<br>* External irradiation 50Gy/5 weeks Lateral: 2 cm lateral to the bony margin of the pelvis Superior: Between L5 and S1 Inferior: 2 cm below the obturator foramen Intracavitary boost 30-35Gy/4 weeks(positive vaginal margins only)<br>|
| Experimental: Concurrent chemoirradiation (CCRT)<br>Concurrent chemoirradiation: External beam radiation with concurrent weekly platinum chemotherapy | Other: Concurrent chemoirradiation (CCRT)<br>* Cisplatin 40mg/m2 every week during external irradiation<br>|
| Experimental: Sequence chemo and radiation (SCRT)<br>Sequence chemotherapy and radiotherapy: 2 cycles chemotherapy of Paclitaxel and Cisplatin before and after the irradiation | Other: Sequence chemotherapy and radiotherapy (SCRT)<br>* Paclitaxel 135 175mg/m2 over 3 hours Cisplatin 60 75mg/m2<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival | DFS survival analysis | 3-Yr | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | OS survival analysis | 5-Yr | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cervical cancer, Concurrent chemoradiation, Randomized controlled clinical trials