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

Study Type:	Interventional
Study Design:	Randomized, Open Label, Active Control, Parallel Assignment
Condition:	Cancer of Cervix
Interventions:	Drug: Gemcitabine Drug: Cisplatin Radiation: Brachytherapy Radiation: Pelvic radiation

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Gemcitabine/Cisplatin/Radiation	Gemcitabine: 125 mg/m2, once weekly (QW), intravenous (IV), 6 weeks Cisplatin: 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks 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, 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
Cisplatin/Radiation	Cisplatin: 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks Pelvic radiation: 1.8 Gy/day, 5 days/week, 6 weeks Brachytherapy, 30-35 Gy over 1 week

Description

Gemcitabine/Cisplatin/Radiation

Gemcitabine: 125 mg/m2, once weekly (QW), intravenous (IV), 6 weeks Cisplatin: 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks 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, 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

Cisplatin/Radiation

Cisplatin: 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks Pelvic radiation: 1.8 Gy/day, 5 days/week, 6 weeks

Brachytherapy, 30-35 Gy over 1 week

Participant Flow: Overall Study

	Gemcitabine/Cisplatin/Radiation	Cisplatin/Radiation
STARTED	259	256
COMPLETED	217	244
NOT COMPLETED	42	12
Adverse Event	18	1
Lost to Follow-up	2	0
Patient Moved	0	1
Withdrawal by Subject	9	3
Protocol Entry Criteria Not Met	2	1
Clinical Relapse	2	1
Lack of Efficacy, Progressive Disease	1	2
Lack of Efficacy, Stable Disease	1	0
Physician Decision	3	1
Death from Study Drug Toxicity	2	0
Protocol Violation	1	1
Death from Other Cause	1	0
Reason Not Specified	0	1

Baseline Characteristics

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Reporting Groups

	Description
Gemcitabine/Cisplatin/Radiation	Gemcitabine: 125 mg/m2, once weekly (QW), intravenous (IV), 6 weeks Cisplatin: 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks 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, 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
Cisplatin/Radiation	Cisplatin: 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks Pelvic radiation: 1.8 Gy/day, 5 days/week, 6 weeks Brachytherapy, 30-35 Gy over 1 week

Description

Gemcitabine/Cisplatin/Radiation

Gemcitabine: 125 mg/m2, once weekly (QW), intravenous (IV), 6 weeks Cisplatin: 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks 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, 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

Cisplatin/Radiation

Cisplatin: 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks Pelvic radiation: 1.8 Gy/day, 5 days/week, 6 weeks

Brachytherapy, 30-35 Gy over 1 week

Baseline Measures

	Gemcitabine/Cisplatin/Radiation	Cisplatin/Radiation	Total
Number of Participants [units: participants]	259	256	515
Age [units: years] Mean ± Standard Deviation	45.8 ± 9.8	46.5 ± 9.2	46.1 ± 9.5
Gender [units: participants]
Female	259	256	515
Male	0	0	0
Region of Enrollment [units: participants]
Pakistan	27	29	56
Mexico	28	31	59
Argentina	17	18	35
Thailand	34	33	67
Peru	29	31	60
India	60	56	116
Bosnia and Herzegovina	33	28	61
Panama	31	30	61
Grade of Histological Diagnosis [units: participants]
Moderately Differentiated	114	119	233
Poorly Differentiated	48	44	92
Unknown	69	69	138
Undifferentiated	2	0	2
Well Differentiated	26	24	50
Karnofsky Performance Status Scale^[1] [units: participants]
Unknown (Missing)	1	0	1
70 - Unable to carry on normal activity	0	1	1
80 - Activity with effort; some signs of disease	8	9	17
90 - Normal activity; minor signs of disease	147	145	292
100 - Normal no complaints; no evidence of disease	103	101	204
Pathological Diagnosis [units: participants]
Adenocarcinoma of Cervix	17	15	32
Adeno/Squamous Cell Carcinoma	198	199	397
Other - Poorly Differentiated Carcinoma	1	0	1
Other - Squamous	43	42	85
Race/Ethnicity [units: participants]
Western Asian	87	85	172
Caucasian	33	29	62
East/Southeast Asian	34	33	67
Hispanic	105	109	214
Stage of Disease [units: participants]
Stage IIIA	1	1	2
Stage IIIB	94	94	188
Stage IIB	160	156	316
Stage IVA	4	5	9
Height [units: centimeters] Mean ± Standard Deviation	155.2 ± 6.6	154.6 ± 6.7	154.9 ± 6.6
Weight [units: kilograms] Mean ± Standard Deviation	61.2 ± 11.3	62.4 ± 13.0	61.8 ± 12.2

[1]	Classifies patients according to their functional impairment. Scores range from 0-100, the lower the score, the worse the survival for most serious illnesses.

Outcome Measures

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1. Primary:

Number of Participants With Progressive Disease or Death Due to Any Cause at 3 Years [ 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 ]

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Measure Type	Primary
Measure Title	Number of Participants With Progressive Disease or Death Due to Any Cause at 3 Years
Measure Description	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.
Time Frame	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention-to-treat population includes all randomized participants. Participants were analyzed according to treatment they were randomly assigned.

Reporting Groups

	Description
Gemcitabine/Cisplatin/Radiation	Gemcitabine: 125 mg/m2, once weekly (QW), intravenous (IV), 6 weeks Cisplatin: 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks 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, 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
Cisplatin/Radiation	Cisplatin: 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks Pelvic radiation: 1.8 Gy/day, 5 days/week, 6 weeks Brachytherapy, 30-35 Gy over 1 week

Description

Gemcitabine/Cisplatin/Radiation

Gemcitabine: 125 mg/m2, once weekly (QW), intravenous (IV), 6 weeks Cisplatin: 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks 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, 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

Cisplatin/Radiation

Cisplatin: 40 mg/m2, once weekly (QW), intravenous (IV), 6 weeks Pelvic radiation: 1.8 Gy/day, 5 days/week, 6 weeks

Brachytherapy, 30-35 Gy over 1 week

Measured Values

	Gemcitabine/Cisplatin/Radiation	Cisplatin/Radiation
Number of Participants Analyzed [units: participants]	259	256
Number of Participants With Progressive Disease or Death Due to Any Cause at 3 Years [units: participants]
3 Years: Number of Patients with Event	55	83
3 Years: Number of Patients at Risk	149	141

Statistical Analysis 1 for Number of Participants With Progressive Disease or Death Due to Any Cause at 3 Years

Groups ^[1]	All groups
Method ^[2]	Z Statistic
P Value ^[3]	0.029
PFS Probability Difference at 3 Years ^[4]	0.095
95% Confidence Interval	( 0.010 to 0.179 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The p-value is two-sided and was tested at the 0.05 significance level.
[4]	Other relevant estimation information:
	Difference in progression-free survival probability between Gem/Cis/Rad and Cis/Rad. The difference in PFS probability between the two treatment arms can also be presented as a percentage (ie, PFS at 3 years was 9.5% better in the Gem/Cis/Rad arm).

2. Secondary:

Number of Participants With Progressive Disease or Death Due to Disease Under Study at Various Time Points [ 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 ]

Show Outcome Measure 2

3. Secondary:

Local Failure Rate [ 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 ]

Show Outcome Measure 3

4. Secondary:

Tumor 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 ]

Show Outcome Measure 4

5. Secondary:

Number of Participants Who Died From Any Cause at Various Time Points [ baseline to date of death from any cause (includes 60 month follow-up period) ]

Show Outcome Measure 5

6. Secondary:

Number of Participants With Progressive Disease or Death Due to Any Cause at Various Time Points [ 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 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 1-800-545-5979

No publications provided

Responsible Party:	Eli Lilly ( Chief Medical Officer )
Study ID Numbers:	4015, B9E-MC-JHQS
Study First Received:	September 12, 2005
Results First Received:	March 30, 2009
Last Updated:	August 8, 2009
ClinicalTrials.gov Identifier:	NCT00191100 History of Changes
Health Authority:	Mexico: National Institute of Public Health, Health Secretariat