Study on Early Stage Bulky Cervical Cancers

Study Overview
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Brief Summary
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The aim of this study is to establish the role of neoadjuvant chemotherapy and chemo irradiation in carcinoma cervix and to compare its results with the concurrent chemo irradiation in terms of overall survival, disease free survival and quality of life.

Detailed Description
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Early stage bulky cancers of the cervix, (defined as FIGO Stages IB2, IIA2 and IIB) form a distinctive subset of curable cervical cancers with good 5 year survival rates with adequate treatment. Concurrent chemo radiation with or without salvage surgery is at present the standard of care for this group of cervical cancers. However, when pelvic recurrences occur, the morbidity of salvage surgery after radiotherapy, especially brachytherapy is often higher than the morbidity of salvage radiotherapy following radical surgery. The advantages of downsizing the disease without the use of brachytherapy are tempting and open a completely new philosophy in radical treatment for curable early stage bulky cancers of the cervix. This approach is appealing especially in developing countries where the load of cervical cancers is high and radiotherapy (brachytherapy) resources are scarce. The results of two Phase II trials conducted at Govt. Royapettah Hospital, Chennai (Neoadjuvant Chemotherapy followed by Radical Hysterectomy: Cisplatin + 5FU vs. Cisplatin +Paclitaxel) and at Govt. General Hospital,Chennai (Neoadjuvant Chemoradiation with weekly cisplatin and 50 EBRT followed by radical Hysterectomy) and one retrospective study ( Preoperative 50 GY EBRT followed by Radical Hysterectomy) have shown similar response rates and acceptable toxicity profiles when compared to concurrent chemoradiation (EBRT + Brachytherapy+ Chemotherapy). Similar studies have been published elsewhere with similar results. With this in mind we are planning to conduct a Phase III Randomised control trial comparing Neoadjuvant Chemotherapy + Radical Hysterectomy and Neoadjuvant Chemoradiation + Radical Hysterectomy with concurrent chemoradiation in this subset of cervical cancers

Official Title
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Randomised Phase III Clinical Trial on Concurent Chemoradiation vs. Neoadjuvant Chemoradiation and Surgery vs. Neoadjuvant Chemotherapy and Surgery in Early Stage Bulky Cervical Cancers (FIGO Stages IB2, IIA2 and IIB)

Conditions
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Carcinoma Cervix

Intervention / Treatment
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* Drug: Chemotherapy
* Radiation: External Beam Radiotherapy
* Radiation: Brachytherapy
* Procedure: Radical Hysterectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed bulky cervical Squamous cell carcinoma (FIGO stage IB2, II A2, IIB). Age 18-60 years Karnofsky performance status of ≥70%; ECOG PS ≤ 2 Exclusion Criteria: Nonsquamous Histologies Other systemic diseases, comorbidities precluding full participation in the study Concomitant treatment with any experimental drug Pregnant or nursing women Previous or concomitant malignant diseases other than non-melanoma skin cancer Previous radiation to the pelvis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Concurrent Radical Chemoradiation<br>Paclitaxel(175 mg/sq.m) + Cisplatin (75 mg/sq.m) chemotherapy - 2 cycles of 3 weekly cycle Concurrent Radiotherapy - 50 Gy EBRT + Brachytherapy (7Gy HDR x 3 doses) All to be completed within 8-10 weeks | Drug: Chemotherapy<br>* cisplatin 75 mg/m2 Paclitaxel 175 mg/m2<br>Radiation: External Beam Radiotherapy<br>* 50 Gy/2 Gy/25 # external beam RT to cervix. four field technique. given concurrently with chemotherapy weeks 1 - 5<br>Radiation: Brachytherapy<br>* Ir - 192 HDR Brachytherapy - intracavitary. 7Gy x 3#. given after completion of chemoRT.<br>|
| Experimental: Neoadjuvant Chemoradiation + Radical Hysterectomy<br>Paclitaxel(175 mg/m2) + Cisplatin(75 mg/m2) chemotherapy - 2 cycles of 3 weekly cycle Concurrent Radiotherapy - 50 Gy EBRT - completed within 5 weeks Radical Hysterectomy - 3 weeks after completion of RT All to be completed within 8-10 weeks | Drug: Chemotherapy<br>* cisplatin 75 mg/m2 Paclitaxel 175 mg/m2<br>Radiation: External Beam Radiotherapy<br>* 50 Gy/2 Gy/25 # external beam RT to cervix. four field technique. given concurrently with chemotherapy weeks 1 - 5<br>Procedure: Radical Hysterectomy<br>* Type III Radical Hysterectomy + Bilateral Pelvic Node Dissection<br>|
| Experimental: Neoadjuvant Chemotherapy + Radical Hysterectomy<br>Paclitaxel(175 mg/m2) + Cisplatin (75 mg/m2) chemotherapy - 3 cycles of 3 weekly cycle Radical Hysterectomy - 3 weeks after completion of chemotherapy All to be completed within 8-10 weeks | Drug: Chemotherapy<br>* cisplatin 75 mg/m2 Paclitaxel 175 mg/m2<br>Procedure: Radical Hysterectomy<br>* Type III Radical Hysterectomy + Bilateral Pelvic Node Dissection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall and Disease free Survival |  | 3 year | 
| Overall and Disease free Survival |  | 5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Adverse reactions and complications |  | Less than 10 weeks | 
| SubAcute Adverse reactions and complications |  | 10 weeks - 6 months | 
| Chronic Adverse reactions and complications |  | 6 months to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bulky cervical cancers, Neoadjuvant Chemotherapy, Neoadjuvant Chemoradiotherapy