Comparative Study of Gemcitabine,Cisplatin and Radiation Versus Cisplatin and Radiation in Cancer of the Cervix

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness of two methods of treating cancer of the cervix. Half the patients will receive gemcitabine plus cisplatin while undergoing radiation therapy, followed by adjuvant gemcitabine and cisplatin and the other half will receive cisplatin along with radiation therapy without adjuvant therapy.

Official Title
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Phase 3 Randomized Comparison of Concurrent Gemcitabine, Cisplatin, and Radiation Followed by Adjuvant Gemcitabine and Cisplatin Versus Concurrent Cisplatin and Radiation in Cancer of the Cervix Stages IIB to IVA

Conditions
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Cancer of Cervix

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Cisplatin
* Radiation: Brachytherapy
* Radiation: Pelvic radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed with cancer of cervix tumor that can be measured no previous treatment with chemotherapy or radiation for this cancer Karnofsky Performance Status Score >=70 able to give written consent willing and able to participate in the study, both during the active treatment and the follow-up period. Exclusion Criteria: impairment such as hearing loss from prior cisplatin therapy damage to nerves such as being unable to distinguish hot and cold to touch used other experimental medication in past 30 days lab test results are not within the limits required for this study pregnancy or breast-feeding or possibility of becoming pregnant during this study and not using an approved method of birth control.

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 |
| --- | --- |
| Experimental: 1<br>Cisplatin, 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks and Gemcitabine 125 mg/m2, once weekly (QW), intravenous (IV), 6 weeks and Pelvic radiation, 1.8 Gy/day, 5 days/week, 6 weeks Brachytherapy, 30-35 Gy over 1 week Two week rest period with no chemotherapy or radiation Cisplatin, 50 mg/m2, intravenous (IV), day 1 of 21 day cycle for two 21-day cycles and Gemcitabine, 1000 mg/m2, day 1 and day 8 for two 21 day cycles | Drug: Gemcitabine<br> <br> * Other names: Gemzar;Drug: Cisplatin<br> <br> Radiation: Brachytherapy<br>* Brachytherapy, 30-35 Gy over 1 week<br>Radiation: Pelvic radiation<br>* Pelvic radiation, 1.8 Gy/day, 5 days/week, 6 weeks<br>|
| Active Comparator: 2<br>Cisplatin, 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks and Pelvic radiation, 1.8 Gy/day, 5 days/week, 6 weeks Brachytherapy, 30-35 Gy over 1 week | Drug: Cisplatin<br> <br> Radiation: Brachytherapy<br>* Brachytherapy, 30-35 Gy over 1 week<br>Radiation: Pelvic radiation<br>* Pelvic radiation, 1.8 Gy/day, 5 days/week, 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Progressive Disease or Death Due to Any Cause at 3 Years | Original outcome was Progression-Free Survival (PFS) probability at 3 years. PFS=time from baseline to progressive disease (PD) or death from any cause. Probability is not an accepted Measure Type, so number of progression-free patients still at risk and cumulative number of patients that had an event (PD or death of any cause) are presented. | Tumor assessments at baseline, weekly during chemoradiation & brachytherapy, on Day 1 of adjuvant Cycles 1&2 for Arm A, at the 30-day post-study visit, every 4/6 months for 12/48 months of the short/long post-study follow-up periods respectively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Progressive Disease or Death Due to Disease Under Study at Various Time Points | Original outcome was Time to Progressive Disease (TTPD), which is the time from baseline to event (progressive disease or death due to study disease). The median TTPD was not achieved and therefore the cumulative number of participants with event (and those still at risk) at various time points are presented. | Tumor assessments at baseline, weekly during chemoradiation & brachytherapy, on Day 1 of adjuvant Cycles 1&2 for Arm A, at the 30-day post-study visit, every 4/6 months for 12/48 months of the short/long post-study follow-up periods respectively | 
| Local Failure Rate | Local failure rate (LFR) was defined as the the proportion of per-protocol participants who had progressive disease (PD) in the cervix or pelvis. LFR = The number of (a) participants who progressed in the cervix or pelvis divided by (b) the number of participants in each arm. (LFR=a/b). | Tumor assessments at baseline, weekly during chemoradiation & brachytherapy, on Day 1 of adjuvant Cycles 1&2 for Arm A, at the 30-day post-study visit, every 4/6 months for 12/48 months of the short/long post-study follow-up periods respectively | 
| Tumor Response | Tumor response rate (TRR) defined as number of qualified responder patients with confirmed complete or partial response. | Tumor assessments at baseline, weekly during chemoradiation & brachytherapy, on Day 1 of adjuvant Cycles 1&2 for Arm A, at the 30-day post-study visit, every 4/6 months for 12/48 months of the short/long post-study follow-up periods respectively | 
| Number of Participants Who Died From Any Cause at Various Time Points | Original outcome was Overall Survival, which was defined as time from baseline to death from any cause. | baseline to date of death from any cause (includes 60 month follow-up period) | 
| Number of Participants With Progressive Disease or Death Due to Any Cause at Various Time Points | Original outome was Progression-Free Survival, which was defined as time from baseline to progressive disease or death due to any cause. | Tumor assessments at baseline, weekly during chemoradiation & brachytherapy, on Day 1 of adjuvant Cycles 1&2 for Arm A, at the 30-day post-study visit, every 4/6 months for 12/48 months of the short/long post-study follow-up periods respectively |