Prevention And Treatment Of Chemotherapy-Induced Peripheral Neuropathy In Subjects With Advanced Colorectal Cancer

This study has been terminated.

(See detailed description for termination reason)

Sponsor:

Information provided by:

Pfizer

ClinicalTrials.gov Identifier:

NCT00380874

First received: September 25, 2006

Last updated: October 1, 2009

Last verified: October 2009

History of Changes

Results First Received: March 10, 2009

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Chemotherapy-Induced Peripheral Neuropathy
Interventions:	Drug: Pregabalin Drug: Placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 69 subjects screened, 64 were randomized, and 61 received treatment. Of the 8 subjects screened but not treated, 1 was ineligible due to an abnormal laboratory test result, 6 were ineligible due to a reason categorized as other, and 1 was no longer willing to continue in the study.

Reporting Groups

	Description
Pregabalin	Pregabalin 150 to 600 milligrams per day (mg/day) flexible dose + chemotherapy (oxaliplatin combined with 5-fluorouracil/folinic acid (5-FU/FA). Possible dose levels of pregabalin were 150 mg/day (75 mg capsules twice a day [BID]), 300 mg/day (150 mg capsules BID) or 600 mg/day (300 mg capsules BID).
Placebo	matching placebo + chemotherapy (oxaliplatin combined with 5-fluorouracil/folinic acid (5-FU/FA).

Participant Flow: Overall Study

	Pregabalin	Placebo
STARTED	32	29
COMPLETED	19	19
NOT COMPLETED	13	10
Adverse Event	7	7
Death	1	0
Withdrawal by Subject	2	1
Not related to study drug	3	2

Baseline Characteristics

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Reporting Groups

	Description
Pregabalin	Pregabalin 150 to 600 milligrams per day (mg/day) flexible dose + chemotherapy (oxaliplatin combined with 5-fluorouracil/folinic acid (5-FU/FA). Possible dose levels of pregabalin were 150 mg/day (75 mg capsules twice a day [BID]), 300 mg/day (150 mg capsules BID) or 600 mg/day (300 mg capsules BID).
Placebo	matching placebo + chemotherapy (oxaliplatin combined with 5-fluorouracil/folinic acid (5-FU/FA).
Total	Total of all reporting groups

Baseline Measures

	Pregabalin	Placebo	Total
Number of Participants [units: participants]	32	29	61
Age [units: years] Mean ± Standard Deviation	58.9 ± 11.3	56.1 ± 12.9	57.6 ± 12.0
Gender [units: participants]
Female	11	8	19
Male	21	21	42

Outcome Measures

Show All Outcome Measures

1. Primary:

Duration Adjusted Average Change (DAAC) of Paresthesia From the Onset of Chemotherapy Measured by Numeric Rating Scale (NRS) [ Time Frame: Period of 10 days from the onset of chemotherapy to the last cycle: Last Observation Carried Forward (LOCF) ]

Show Outcome Measure 1

2. Secondary:

Duration Adjusted Average Change (DAAC) of Paresthesic Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS) [ Time Frame: Baseline to Cycle 9 ]

Show Outcome Measure 2

3. Secondary:

Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS) [ Time Frame: Baseline to Cycle 9, LOCF cycle endpoint ]

Hide Outcome Measure 3

Measure Type	Secondary
Measure Title	Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS)
Measure Description	Least squares (LS) mean of change: mean at cycle minus mean at Baseline. Dysesthesic Duration Adjusted Average Change (DAAC) endpoint was computed based on Numeric Rating Scale (NRS) of dysesthesis (collected 0=no pain; 1-3=mild pain; 4–6=moderate pain; 7-10=severe pain). DAAC endpoint was defined as the Area Under Curve (AUC) of the collected NRS over time, divided by collection time period (up to 10 days).
Time Frame	Baseline to Cycle 9, LOCF cycle endpoint
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.
ITT population, subjects with at lest 1 dose of study medication and for whom at least 1 post-baseline efficacy evaluation was obtained.

Reporting Groups

	Description
Pregabalin	Pregabalin 150 to 600 milligrams per day (mg/day) flexible dose + chemotherapy (oxaliplatin combined with 5-fluorouracil/folinic acid (5-FU/FA). Possible dose levels of pregabalin were 150 mg/day (75 mg capsules twice a day [BID]), 300 mg/day (150 mg capsules BID) or 600 mg/day (300 mg capsules BID).
Placebo	matching placebo + chemotherapy (oxaliplatin combined with 5-fluorouracil/folinic acid (5-FU/FA).

Measured Values

	Pregabalin	Placebo
Number of Participants Analyzed [units: participants]	32	29
Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS) [units: score on scale] Least Squares Mean ± Standard Error
Cycle 1 (n=25,27)	0.09 ± 0.08	0.13 ± 0.07
Cycle 2 (n=26,26)	0.75 ± 0.25	0.38 ± 0.25
Cycle 3 (n=24,23)	0.91 ± 0.33	0.65 ± 0.34
Cycle 4 (n=25,23)	1.01 ± 0.37	0.71 ± 0.39
Cycle 5 (n=24,22)	1.54 ± 0.48	0.80 ± 0.50
Cycle 6 (n=21,21)	0.88 ± 0.38	0.93 ± 0.38
Cycle 7 (n=17,22)	1.17 ± 0.39	1.17 ± 0.34
Cycle 8 (n=16,19)	1.33 ± 0.40	1.06 ± 0.36
Cycle 9 (n=16, 18)	1.24 ± 0.44	1.75 ± 0.42
LOCF endpoint (n=26, 27)	1.36 ± 0.38	1.33 ± 0.38

Statistical Analysis 1 for Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.7207
Mean Difference (Final Values) ^[4]	-0.04
Standard Error of the mean	± 0.11
95% Confidence Interval	( -0.25 to 0.17 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 1.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Cycle 1. No multiple comparisons adjustment was made.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Model terms include treatment, study center, and baseline score.
[4]	Other relevant estimation information:
	LS means and corresponding standard errors derived from ANCOVA model were used.

Statistical Analysis 2 for Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.3111
Mean Difference (Final Values) ^[4]	0.37
Standard Error of the mean	± 0.36
95% Confidence Interval	( -0.36 to 1.10 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 2.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Model terms include treatment, study center, and baseline score.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No multiple comparisons adjustment was made.
[4]	Other relevant estimation information:
	LS means and corresponding standard errors derived from ANCOVA model were used.

Statistical Analysis 3 for Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.5925
Mean Difference (Final Values) ^[4]	0.26
Standard Error of the mean	± 0.48
95% Confidence Interval	( -0.70 to 1.22 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 3.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Model terms include treatment, study center, and baseline score.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No multiple comparisons adjustment was made.
[4]	Other relevant estimation information:
	LS means and corresponding standard errors derived from ANCOVA model were used.

Statistical Analysis 4 for Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.5812
Mean Difference (Final Values) ^[4]	0.30
Standard Error of the mean	± 0.55
95% Confidence Interval	( -0.80 to 1.41 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 4.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Model terms include treatment, study center, and baseline score.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No multiple comparisons adjustment was made.
[4]	Other relevant estimation information:
	LS means and corresponding standard errors derived from ANCOVA model were used.

Statistical Analysis 5 for Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.2925
Mean Difference (Final Values) ^[4]	0.75
Standard Error of the mean	± 0.70
95% Confidence Interval	( -0.67 to 2.16 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 5.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Model terms include treatment, study center, and baseline score.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No multiple comparisons adjustment was made.
[4]	Other relevant estimation information:
	LS means and corresponding standard errors derived from ANCOVA model were used.

Statistical Analysis 6 for Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.9276
Mean Difference (Final Values) ^[4]	-0.05
Standard Error of the mean	± 0.54
95% Confidence Interval	( -1.15 to 1.05 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 6.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Model terms include treatment, study center, and baseline score.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No multiple comparisons adjustment was made.
[4]	Other relevant estimation information:
	LS means and corresponding standard errors derived from ANCOVA model were used.

Statistical Analysis 7 for Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.9952
Mean Difference (Final Values) ^[4]	0.00
Standard Error of the mean	± 0.53
95% Confidence Interval	( -1.06 to 1.07 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 7.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Model terms include treatment, study center, and baseline score.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 8 for Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.6265
Mean Difference (Final Values) ^[4]	0.27
Standard Error of the mean	± 0.55
95% Confidence Interval	( -0.85 to 1.38 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 8.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Model terms include treatment, study center, and baseline score.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	LS means and corresponding standard errors derived from ANCOVA model were used.

Statistical Analysis 9 for Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.4209
Mean Difference (Final Values) ^[4]	-0.51
Standard Error of the mean	± 0.62
95% Confidence Interval	( -1.77 to 0.76 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Cycle 9.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Model terms include treatment, study center, and baseline score.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No multiple comparisons adjustment was made.
[4]	Other relevant estimation information:
	LS means and corresponding standard errors derived from ANCOVA model were used.

Statistical Analysis 10 for Duration Adjusted Average Change (DAAC) of Dysesthesia Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS)

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.9657
Mean Difference (Final Values) ^[4]	0.02
Standard Error of the mean	± 0.54
95% Confidence Interval	( -1.06 to 1.11 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Last Observation Carried Forward (LOCF)endpoint.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Model terms include treatment, study center, and baseline score.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No multiple comparisons adjustment was made.
[4]	Other relevant estimation information:
	LS means and corresponding standard errors derived from ANCOVA model were used.

4. Secondary:

Duration Adjusted Average Change (DAAC) of Pain Symptom Score Within Each Cycle of Chemotherapy Measured by Numeric Rating Scale (NRS) [ Time Frame: Baseline to Cycle 9, LOCF cycle endpoint ]

Show Outcome Measure 4

5. Secondary:

Change in Pain Scores Rated on Neuropathic Pain Symptom Inventory (NPSI) Subscales From Baseline Cycle [ Time Frame: Baseline to Cycle 9, Last Observation Carried Forward (LOCF) cycle endpoint ]

Show Outcome Measure 5

6. Secondary:

Number of Participants With Persistent Paresthesic, Dysesthesic, and Pain Symptoms [ Time Frame: Cycle 9 and Last Observation Carried Forward (LOCF) cycle endpoint ]

Show Outcome Measure 6

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. Restriction Description: Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.

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
Due to lack of symptom emergence, enrollment was halted, and endpoint modified because primary assumptions upon which it was powered (emergence of symptomatology) were not met, and not all endpoints were able to be reliably analyzed.

Results Point of Contact:

Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc
phone: 1-800-718-1021
e-mail: ClinicalTrials.govCallCenter@pfizer.com

No publications provided

Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier:	NCT00380874 History of Changes
Other Study ID Numbers:	A0081124
Study First Received:	September 25, 2006
Results First Received:	March 10, 2009
Last Updated:	October 1, 2009
Health Authority:	United States: Food and Drug Administration

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