A Study of the Combination of Pemetrexed and Irinotecan Every Two Weeks in Metastatic Colorectal Cancer

• ClinicalTrials.gov Identifier: NCT00191984
• Recruitment Status: Completed
• First Posted: September 19, 2005
• Results First Posted: June 15, 2009
• Last Update Posted: January 5, 2011
• Sponsor: Eli Lilly and Company
• Information provided by: Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Colorectal Cancer
• Interventions: Drug: pemetrexed; Drug: irinotecan
• Enrollment: 46

Participant Flow

Recruitment Details
Pre-assignment Details	Two participants discontinued the trial before receiving study treatment. One due to entry criteria exclusion and one due to withdrawal by subject. Therefore, 44 participants received at least one dose of chemotherapy and are included in the efficacy and safety analyses.

Arm/Group Title	Pemetrexed + Irinotecan
Arm/Group Description	Pemetrexed: 400 mg/m2, intravenous (IV), every 14 days x 12 cycles Irinotecan: 180 mg/m2, intravenous (IV), every 14 days x 12 cycles
Period Title: Overall Study
Started	46
Completed	7
Not Completed	39
Reason Not Completed
Disease Progression	21
Adverse Event	4
Death	2
Entry Criteria Exclusion	1
Withdrawal by Subject	7
Physician Decision	4

Baseline Characteristics

Arm/Group Title		Pemetrexed + Irinotecan
Arm/Group Description		Pemetrexed: 400 mg/m2, intravenous (IV), every 14 days x 12 cycles Irinotecan: 180 mg/m2, intravenous (IV), every 14 days x 12 cycles
Overall Number of Baseline Participants		44
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	44 participants
		60.8 (11.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	44 participants
	Female	13 29.5%
	Male	31 70.5%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
France	Number Analyzed	44 participants
		44
Eastern Cooperative Oncology Group (ECOG) Performance Status [1]; Measure Type: Number; Unit of measure: Units on a scale	Number Analyzed	44 participants
0 - Fully Active		24
1 - Ambulatory, Restricted Strenuous Activity		15
2 - Ambulatory, No Work Activities		5
		[1] Measure Description: Classifies patients according to their functional impairment. Scores range from 0 (Fully Active) to 5 (Death).
Pathological Diagnosis; Measure Type: Number; Unit of measure: Participants	Number Analyzed	44 participants
Adenocarcinoma of Colon		22
Adenocarcinoma of Rectum		20
Colorectal Cancer		2
Height; Mean (Standard Deviation); Unit of measure: Centimeters
	Number Analyzed	44 participants
		169.3 (8.5)
Weight; Mean (Standard Deviation); Unit of measure: Kilograms
	Number Analyzed	44 participants
		69.3 (11.7)

Outcome Measures

1. Primary Outcome

Title	Best Overall Tumor Response
Description	Best response recorded from the start of treatment until disease progression/recurrence using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve ("respond"), stay the same ("stable"), or worsen ("progression") during treatment. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) = small changes that do not meet above criteria.
Time Frame	baseline to measured progressive disease (up to 2 years follow-up)

Outcome Measure Data

Analysis Population Description

All enrolled participants with at least one completed cycle.

Arm/Group Title	Pemetrexed + Irinotecan
Arm/Group Description:	Pemetrexed: 400 mg/m2, intravenous (IV), every 14 days x 12 cycles Irinotecan: 180 mg/m2, intravenous (IV), every 14 days x 12 cycles
Overall Number of Participants Analyzed	44
Measure Type: Number; Unit of Measure: participants
Partial Response	6
Stable Disease	18
Progressive Disease	15
Unknown	5

2. Secondary Outcome

Title	Duration of Response
Description	The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. Response was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria that defines when participants improve ("respond"), stay the same ("stable"), or worsen ("progression") during treatment. Complete response (CR) = disappearance of all target lesions. Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions.
Time Frame	time of response to progressive disease or death (up to 2 years follow-up)

Outcome Measure Data

Analysis Population Description

All enrolled participants with at least completed cycle and who had a complete or partial response.

Arm/Group Title	Pemetrexed + Irinotecan
Arm/Group Description:	Pemetrexed: 400 mg/m2, intravenous (IV), every 14 days x 12 cycles Irinotecan: 180 mg/m2, intravenous (IV), every 14 days x 12 cycles
Overall Number of Participants Analyzed	6
Median (95% Confidence Interval); Unit of Measure: days
	236; (105 to 353)

3. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	Defined as the time from study enrollment to the first date of disease progression or death as a result of any cause. PFS was censored at the date of the last follow-up visit for participants who were still alive and who had not progressed.
Time Frame	baseline to measured progressive disease or death (up to 2 years follow-up)

Outcome Measure Data

Analysis Population Description

All enrolled participants with at least one completed cycle.

Arm/Group Title	Pemetrexed + Irinotecan
Arm/Group Description:	Pemetrexed: 400 mg/m2, intravenous (IV), every 14 days x 12 cycles Irinotecan: 180 mg/m2, intravenous (IV), every 14 days x 12 cycles
Overall Number of Participants Analyzed	44
Median (95% Confidence Interval); Unit of Measure: days
	123; (60 to 146)

4. Secondary Outcome

Title	Time to Treatment Failure
Description	Defined as the time from study enrollment to the first observation of disease progression, death as a result of any cause, or early discontinuation of treatment. Time to treatment failure was censored at the date of the last follow-up visit for patients who did not discontinue early, who were still alive, and who have not progressed.
Time Frame	baseline to stopping treatment (up to 2 years follow-up)

Outcome Measure Data

Analysis Population Description

All enrolled participants with at least one completed cycle.

Arm/Group Title	Pemetrexed + Irinotecan
Arm/Group Description:	Pemetrexed: 400 mg/m2, intravenous (IV), every 14 days x 12 cycles Irinotecan: 180 mg/m2, intravenous (IV), every 14 days x 12 cycles
Overall Number of Participants Analyzed	44
Median (95% Confidence Interval); Unit of Measure: days
	66; (55 to 105)

5. Secondary Outcome

Title	Overall Survival
Description	Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact.
Time Frame	baseline to date of death from any cause (up to 2 years follow-up)

Outcome Measure Data

Analysis Population Description

All enrolled participants with at least one completed cycle.

Arm/Group Title	Pemetrexed + Irinotecan
Arm/Group Description:	Pemetrexed: 400 mg/m2, intravenous (IV), every 14 days x 12 cycles Irinotecan: 180 mg/m2, intravenous (IV), every 14 days x 12 cycles
Overall Number of Participants Analyzed	44
Median (95% Confidence Interval); Unit of Measure: days
	422; (305 to 602)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Pemetrexed + Irinotecan
Arm/Group Description	Pemetrexed: 400 mg/m2, intravenous (IV), every 14 days x 12 cycles Irinotecan: 180 mg/m2, intravenous (IV), every 14 days x 12 cycles
All-Cause Mortality
	Pemetrexed + Irinotecan
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Pemetrexed + Irinotecan
	Affected / at Risk (%)	# Events
Total	13
Blood and lymphatic system disorders
Anaemia † 1	3/44 (6.82%)	3
Febrile neutropenia † 1	1/44 (2.27%)	1
Gastrointestinal disorders
Diarrhoea † 1	3/44 (6.82%)	4
Melaena † 1	1/44 (2.27%)	1
Nausea † 1	1/44 (2.27%)	1
Vomiting † 1	2/44 (4.55%)	2
General disorders
Asthenia † 1	1/44 (2.27%)	1
General physical health deterioration † 1	1/44 (2.27%)	1
Pyrexia † 1	1/44 (2.27%)	1
Hepatobiliary disorders
Hepatic pain † 1	1/44 (2.27%)	1
Immune system disorders
Hypersensitivity † 1	1/44 (2.27%)	1
Infections and infestations
Septic shock † 1	1/44 (2.27%)	1
Metabolism and nutrition disorders
Dehydration † 1	2/44 (4.55%)	2
Diabetes mellitus insulin-dependent † 1	1/44 (2.27%)	1
Musculoskeletal and connective tissue disorders
Bone pain † 1	1/44 (2.27%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	2/44 (4.55%)	2
Hypoxia † 1	1/44 (2.27%)	1
Skin and subcutaneous tissue disorders
Rash † 1	1/44 (2.27%)	1
Vascular disorders
Hypertensive crisis † 1	1/44 (2.27%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 7.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pemetrexed + Irinotecan
	Affected / at Risk (%)	# Events
Total	38
Blood and lymphatic system disorders
Anaemia † 1	10/44 (22.73%)	11
Neutropenia † 1	7/44 (15.91%)	11
Eye disorders
Conjunctivitis † 1	4/44 (9.09%)	5
Gastrointestinal disorders
Abdominal pain † 1	6/44 (13.64%)	10
Constipation † 1	8/44 (18.18%)	10
Diarrhoea † 1	15/44 (34.09%)	24
Nausea † 1	18/44 (40.91%)	38
Vomiting † 1	11/44 (25.00%)	24
General disorders
Asthenia † 1	24/44 (54.55%)	29
Mucosal inflammation † 1	4/44 (9.09%)	10
Pyrexia † 1	6/44 (13.64%)	12
Investigations
Alanine aminotransferase increased † 1	4/44 (9.09%)	5
Aspartate aminotransferase increased † 1	3/44 (6.82%)	3
Weight decreased † 1	9/44 (20.45%)	9
Weight increased † 1	3/44 (6.82%)	3
Metabolism and nutrition disorders
Anorexia † 1	8/44 (18.18%)	9
Psychiatric disorders
Anxiety † 1	3/44 (6.82%)	3
Skin and subcutaneous tissue disorders
Alopecia † 1	3/44 (6.82%)	3
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 7.0

Limitations and Caveats

[Not Specified]

More Information

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.

Results Point of Contact

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

Publications of Results:

Louvet C, André T, Gamelin E, Hebbar M, Mabro M, Bennamoun M, Rassam H, de Gramont A. Phase II Study of Biweekly Pemetrexed Plus Irinotecan as Second-Line Therapy for Metastatic Colorectal Cancer. J Oncol. 2010;2010:785934. doi: 10.1155/2010/785934. Epub 2010 Apr 8.

• Responsible Party: Chief Medical Officer, Eli Lilly
• ClinicalTrials.gov Identifier: NCT00191984
• Other Study ID Numbers: 8673; H3E-FP-S057 ( Other Identifier: Eli Lilly and Company )
• First Submitted: September 12, 2005
• First Posted: September 19, 2005
• Results First Submitted: April 27, 2009
• Results First Posted: June 15, 2009
• Last Update Posted: January 5, 2011