Dosage Schedule Study of Pemetrexed Monochemotherapy for Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

This study has been completed.

Sponsor:

Information provided by:

Eli Lilly and Company

ClinicalTrials.gov Identifier:

NCT00370292

First received: August 29, 2006

Last updated: October 15, 2009

Last verified: October 2009

History of Changes

Results First Received: September 9, 2009

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Non Small Cell Lung Cancer
Interventions:	Drug: Pemetrexed - Before Protocol Amendment Drug: Pemetrexed - After Protocol Amendment

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 19 enrolled patients, 12 were enrolled before the protocol amendment was made effective (i.e. 2-weekly administration) and 7 were enrolled after the amendment (i.e. 3-weekly administration).

Reporting Groups

	Description
Pemetrexed	500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles (pre-amendement) or 21 days x 6 cycles (post-amendment) or disease progression, unacceptable toxicity or patient decision to discontinue.

Participant Flow: Overall Study

	Pemetrexed
STARTED	19
COMPLETED	6
NOT COMPLETED	13
Disease Progression	4
Adverse Event	7
Physician Decision	2

Baseline Characteristics

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Reporting Groups

	Description
Pemetrexed - Before Amendment	500 milligrams per square meter (mg/m2), intravenous (IV), every 14 days x 8 cycles or disease progression, unacceptable toxicity or patient decision to discontinue.
Pemetrexed - After Amendment	500 milligrams per square meter (mg/m2), intravenous (IV), every 21 days x 6 cycles or disease progression, unacceptable toxicity or patient decision to discontinue.
Total	Total of all reporting groups

Baseline Measures

	Pemetrexed - Before Amendment	Pemetrexed - After Amendment	Total
Number of Participants [units: participants]	12	7	19
Age [units: years] Mean ± Standard Deviation	69.1 ± 10.34	69.4 ± 6.45	69.2 ± 8.90
Gender [units: participants]
Female	3	5	8
Male	9	2	11
Region of Enrollment [units: participants]
Italy	12	7	19
Disease Stages ^[1] [units: participants]
Not Known	0	1	1
Stage IA	2	0	2
Stage IB	1	0	1
Stage IIA	1	0	1
Stage IIB	0	1	1
Stage IIIA	0	1	1
Stage IIIB	3	2	5
Stage IV	5	2	7
Eastern Cooperative Oncology Group Performance Status ^[2] [units: participants]
0 - Fully Active	4	1	5
1 - Ambulatory, Restricted Strenuous Activity	6	5	11
2 - Ambulatory, No Work Activities	2	1	3
Histopathological Grade ^[3] [units: participants]
Not Done	7	2	9
G1 - Well-Differentiated	1	1	2
G2 - Moderately Differentiated	2	1	3
G3 - Poorly Differentiated	2	3	5
Previous Anti-Tumor Treatment [units: participants]
No	5	1	6
Yes	7	6	13
Previous Surgery ^[4] [units: participants]
Surgery - No	4	1	5
Surgery - Yes: Pneumonectomy	0	1	1
Surgery - Yes: Lobectomy	3	3	6
Surgery - Yes: Other	5	3	8
Surgery - Yes: Radical	5	4	9
Race/Ethnicity [units: participants]
Caucasian	12	7	19
Tumor Type [units: participants]
Adenocarcinoma	5	6	11
Squamous Cell Carcinoma	5	1	6
Other	2	0	2
Blood Pressure [units: mmHg] Mean ± Standard Deviation
Systolic Blood Pressure (SBP)	138.0 ± 13.17	146.9 ± 21.54	141.6 ± 17.08
Diastolic Blood Pressure (DBP)	81.8 ± 7.97	83.6 ± 9.45	82.5 ± 8.37
Body Surface Area (BSA) ^[5] [units: square meters (m^2)] Mean ± Standard Deviation	1.7 ± 0.17	1.7 ± 0.13	1.7 ± 0.16
Body Temperature [units: degrees Celsius (°C)] Mean ± Standard Deviation	36.1 ± 0.58	35.9 ± 0.36	36.0 ± 0.49
Heart Rate [units: beats per minute (bpm)] Mean ± Standard Deviation	82.9 ± 14.98	78.6 ± 8.52	81.1 ± 12.58
Height ^[6] [units: centimeters (cm)] Mean ± Standard Deviation	169.2 ± 10.15	162.1 ± 9.04	166.4 ± 10.09
Weight ^[7] [units: kilograms (kg)] Mean ± Standard Deviation	70.2 ± 15.28	66.3 ± 9.43	68.7 ± 13.13

[1]	Stage means how big the tumor is and how far it's spread. Stages range from 0 (tumor has not spread) to IV (tumor has spread to other organs).
[2]	Classifies patients according to their functional impairment. Scores range from 0 (Fully Active) to 5 (Death).
[3]	Assesses the extent to which cancer cells are similar in appearance and function to healthy cells of the same tissue type. Grades range from 1 (least aggressive and best prognosis) to 4 (most aggressive and worst prognosis).
[4]	Participants having surgery could have more than one type of surgery.
[5]	BSA = 0.007184 x weight(kg)^0.425 x height(cm)^0.725
[6]	One participant in the Pemetrexed - Before Amendment group was missing a baseline height measurement.
[7]	One participant in the Pemetrexed - Before Amendment group was missing a baseline weight measurement.

Outcome Measures

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1. Primary:

Mean Deoxycytidine Kinase (dCK) Expression Evaluated at Cycle 1, Cycle 2, and Cycle 3 [ Time Frame: pre-dose, 1, 2, 4, 6, 24, and 48 hours post-dose (3 cycles) ]

Show Outcome Measure 1

2. Primary:

Mean Human Equilibrative Nucleoside Transporter 1 (hENT) Expression Evaluated at Cycle 1, Cycle 2, and Cycle 3 [ Time Frame: pre-dose, 1, 2, 4, 6, 24, and 48 hours post-dose (3 cycles) ]

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Measure Type	Primary
Measure Title	Mean Human Equilibrative Nucleoside Transporter 1 (hENT) Expression Evaluated at Cycle 1, Cycle 2, and Cycle 3
Measure Description	dCK (see Outcome #1)and hENT expression (see Outcome #2) on normal lymphocytes were measured after Pemetrexed administration to evaluate if there was reproducible timing of maximum dCK expression, and to assess proper time interval between pemetrexed and gemcitabine for treatment of patients with advanced Non-Small Cell Lung Cancer (NSCLC). Values are calculated as ratio between thereshold cycles (number of polymerase chain reaction [PCR] cycles) with respect to a reference gene; in this case glyceraldehyde 3-phosphate dehydrogenase (GAPDH).
Time Frame	pre-dose, 1, 2, 4, 6, 24, and 48 hours post-dose (3 cycles)
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.
Number of participants who received at least one dose of study drug.

Reporting Groups

	Description
hENT - Cycle 1	Mean hENT expression evaluated at Cycle 1.
hENT - Cycle 2	Mean hENT expression evaluated at Cycle 2.
hENT - Cycle 3	Mean hENT expression evaluated at Cycle 3.

Measured Values

	hENT - Cycle 1	hENT - Cycle 2	hENT - Cycle 3
Number of Participants Analyzed [units: participants]	19	19	19
Mean Human Equilibrative Nucleoside Transporter 1 (hENT) Expression Evaluated at Cycle 1, Cycle 2, and Cycle 3 [units: mRNA relative values (ratio with GAPDH)] Mean ± Standard Deviation
Pre-Dose	0.86 ± 0.03	0.86 ± 0.03	0.87 ± 0.02
1 Hour Post-Dose	0.88 ± 0.04	0.89 ± 0.04	0.90 ± 0.03
2 Hours Post-Dose	0.88 ± 0.04	0.90 ± 0.04	0.90 ± 0.04
4 Hours Post-Dose	0.86 ± 0.04	0.88 ± 0.05	0.86 ± 0.03
6 Hours Post-Dose	0.86 ± 0.04	0.86 ± 0.04	0.86 ± 0.02
24 Hours Post-Dose	0.89 ± 0.04	0.91 ± 0.04	0.91 ± 0.02
48 Hours Post-Dose	0.90 ± 0.04	0.91 ± 0.04	0.91 ± 0.02

Statistical Analysis 1 for Mean Human Equilibrative Nucleoside Transporter 1 (hENT) Expression Evaluated at Cycle 1, Cycle 2, and Cycle 3

Groups ^[1]	All groups
Method ^[2]	Repeated Measures Analysis of Variance
P Value ^[3]	<0.001

[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:
	P-value for 1 Hour Post-Dose (1 hour across cycles compared with pre-dose across cycles).

Statistical Analysis 2 for Mean Human Equilibrative Nucleoside Transporter 1 (hENT) Expression Evaluated at Cycle 1, Cycle 2, and Cycle 3

Groups ^[1]	All groups
Method ^[2]	Repeated Measures Analysis of Variance
P Value ^[3]	<0.001

[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:
	P-value for 2 Hours Post-Dose (2 hours across cycles compared with pre-dose across cycles).

Statistical Analysis 3 for Mean Human Equilibrative Nucleoside Transporter 1 (hENT) Expression Evaluated at Cycle 1, Cycle 2, and Cycle 3

Groups ^[1]	All groups
Method ^[2]	Repeated Measures Analysis of Variance
P Value ^[3]	0.333

[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:
	P-value for 4 Hours Post-Dose (4 hours across cycles compared with pre-dose across cycles).

Statistical Analysis 4 for Mean Human Equilibrative Nucleoside Transporter 1 (hENT) Expression Evaluated at Cycle 1, Cycle 2, and Cycle 3

Groups ^[1]	All groups
Method ^[2]	Repeated Measures Analysis of Variance
P Value ^[3]	0.849

[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:
	P-value for 6 Hours Post-Dose (6 hours across cycles compared with pre-dose across cycles).

Statistical Analysis 5 for Mean Human Equilibrative Nucleoside Transporter 1 (hENT) Expression Evaluated at Cycle 1, Cycle 2, and Cycle 3

Groups ^[1]	All groups
Method ^[2]	Repeated Measures Analysis of Variance
P Value ^[3]	<0.001

[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:
	P-value for 24 Hours Post-Dose (24 hours across cycles compared with pre-dose across cycles).

Statistical Analysis 6 for Mean Human Equilibrative Nucleoside Transporter 1 (hENT) Expression Evaluated at Cycle 1, Cycle 2, and Cycle 3

Groups ^[1]	All groups
Method ^[2]	Repeated Measures Analysis of Variance
P Value ^[3]	<0.001

[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:
	P-value for 48 Hours Post-Dose (48 hours across cycles compared with pre-dose across cycles).

3. Secondary:

Best Objective Tumor Response [ Time Frame: baseline to measured response (every 14 days for 6 cycles) ]

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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
No text entered.

Results Point of Contact:

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

No publications provided

Responsible Party:	Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier:	NCT00370292 History of Changes
Other Study ID Numbers:	10940, H3E-IT-S105
Study First Received:	August 29, 2006
Results First Received:	September 9, 2009
Last Updated:	October 15, 2009
Health Authority:	Italy: Ministry of Health

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