Study of Pemetrexed Plus Cisplatin in Advanced Gastric Cancer

• ClinicalTrials.gov Identifier: NCT00320515
• Recruitment Status: Completed
• First Posted: May 3, 2006
• Results First Posted: September 28, 2009
• Last Update Posted: September 28, 2009
• 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: Neoplasm, Gastric
• Interventions: Drug: pemetrexed; Drug: cisplatin
• Enrollment: 89

Participant Flow

Recruitment Details
Pre-assignment Details	This was a Phase 1/2 trial. There were 16 participants in Phase 1. None of them qualified for the Phase 2 portion of the trial. There were 73 participants in Phase 2; however, 4 were excluded from all analyses due to data quality issues at one site. Results presented here are for the 69 participants in Phase 2.

Arm/Group Title	Pemetrexed + Cisplatin
Arm/Group Description	Pemetrexed: 700 mg/m2, intravenous (IV), every 21 days, until disease progression Cisplatin: 75 mg/m2, intravenous (IV), every 21 days, until disease progression
Period Title: Overall Study
Started	69
Completed	20
Not Completed	49
Reason Not Completed
Death	33
Lost to Follow-up	6
Physician Decision	2
Withdrawal by Subject	8

Baseline Characteristics

Arm/Group Title		Pemetrexed + Cisplatin
Arm/Group Description		Pemetrexed: 700 mg/m2, intravenous (IV), every 21 days, until disease progression Cisplatin: 75 mg/m2, intravenous (IV), every 21 days, until disease progression
Overall Number of Baseline Participants		69
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	69 participants
		55.9 (10.20)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	69 participants
	Female	20 29.0%
	Male	49 71.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	69 participants
Taiwan		22
Mexico		4
Argentina		18
Korea, Republic of		25
Eastern Cooperative Oncology Group Performance Status [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	69 participants
0 - Fully Active		42
1 - Ambulatory, Restricted Strenuous Activity		27
		[1] Measure Description: Classifies patients according to their functional impairment. Scores range from 0 (Fully Active) to 5 (Death).
Race/Ethnicity; Measure Type: Number; Unit of measure: Participants	Number Analyzed	69 participants
Caucasian		1
East Asian		47
Hispanic		21

Outcome Measures

1. Primary Outcome

Title	Objective Best Tumor Response
Description	Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria.
Time Frame	baseline to measured progressive disease (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until disease progression, or up to 12 months after enrollment)

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug. One participant was excluded from analysis because of no measurable disease at baseline.

Arm/Group Title	Pemetrexed + Cisplatin
Arm/Group Description:	Pemetrexed: 700 mg/m2, intravenous (IV), every 21 days, until disease progression Cisplatin: 75 mg/m2, intravenous (IV), every 21 days, until disease progression
Overall Number of Participants Analyzed	68
Measure Type: Number; Unit of Measure: participants
Complete Response	1
Partial Response	15
Stable Disease	22
Progressive Disease	24
Unknown	6

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.
Time Frame	time of response to progressive disease or death (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until disease progression, or up to 12 months after enrollment)

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug, had measureable disease at baseline, and had confirmed complete or partial responses. There were 16 patients qualified for the analysis of duration of response. Twelve participants were censored.

Arm/Group Title	Pemetrexed + Cisplatin
Arm/Group Description:	Pemetrexed: 700 mg/m2, intravenous (IV), every 21 days, until disease progression Cisplatin: 75 mg/m2, intravenous (IV), every 21 days, until disease progression
Overall Number of Participants Analyzed	16
Median (95% Confidence Interval); Unit of Measure: months
	5.4; (4.6 to 6.9)

3. Secondary Outcome

Title	Progression Free Survival
Description	The period from study entry until disease progression or death on study, whichever occurred first.
Time Frame	baseline to measured progressive disease or death (Tumor assessments were performed every 2 cycles during therapy and 6-8 weeks during post-therapy until disease progression, or up to 12 months after enrollment)

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and had measureable disease at baseline. Twenty-six participants were censored.

Arm/Group Title	Pemetrexed + Cisplatin
Arm/Group Description:	Pemetrexed: 700 mg/m2, intravenous (IV), every 21 days, until disease progression Cisplatin: 75 mg/m2, intravenous (IV), every 21 days, until disease progression
Overall Number of Participants Analyzed	68
Median (95% Confidence Interval); Unit of Measure: months
	4.9; (2.8 to 7.1)

4. 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 (Survival follow-up were performed every 2 cycles during therapy and approximately every 3 months during post-therapy until death or up to 12 months after enrollment)

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least one dose of study drug and had measurable disease at baseline. Thirty-five participants were censored.

Arm/Group Title	Pemetrexed + Cisplatin
Arm/Group Description:	Pemetrexed: 700 mg/m2, intravenous (IV), every 21 days, until disease progression Cisplatin: 75 mg/m2, intravenous (IV), every 21 days, until disease progression
Overall Number of Participants Analyzed	68
Median (95% Confidence Interval); Unit of Measure: months
	11.8; (7.2 to 18.5)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Pemetrexed + Cisplatin
Arm/Group Description	Pemetrexed: 700 mg/m2, intravenous (IV), every 21 days, until disease progression Cisplatin: 75 mg/m2, intravenous (IV), every 21 days, until disease progression
All-Cause Mortality
	Pemetrexed + Cisplatin
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Pemetrexed + Cisplatin
	Affected / at Risk (%)	# Events
Total	14
Blood and lymphatic system disorders
Neutropenia † 1	1/69 (1.45%)	1
Gastrointestinal disorders
Abdominal pain † 1	1/69 (1.45%)	1
Abdominal pain upper † 1	1/69 (1.45%)	1
Ascites † 1	1/69 (1.45%)	1
Colonic obstruction † 1	1/69 (1.45%)	1
Ileus † 1	2/69 (2.90%)	2
Upper gastrointestinal haemorrhage † 1	2/69 (2.90%)	2
Vomiting † 1	1/69 (1.45%)	1
Metabolism and nutrition disorders
Dehydration † 1	1/69 (1.45%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage † 1	1/69 (1.45%)	1
Nervous system disorders
Central nervous system lesion † 1	1/69 (1.45%)	1
Ischaemic cerebral infarction † 1	1/69 (1.45%)	1
Renal and urinary disorders
Renal failure † 1	1/69 (1.45%)	1
Respiratory, thoracic and mediastinal disorders
Asthmatic crisis † 1	1/69 (1.45%)	1
Dyspnoea † 1	1/69 (1.45%)	1
Pulmonary embolism † 1	1/69 (1.45%)	1
Vascular disorders
Deep vein thrombosis † 1	1/69 (1.45%)	1
Hypotension † 1	1/69 (1.45%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 11.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pemetrexed + Cisplatin
	Affected / at Risk (%)	# Events
Total	69
Blood and lymphatic system disorders
Anaemia † 1	13/69 (18.84%)	24
Leukopenia † 1	6/69 (8.70%)	9
Lymphopenia † 1	12/69 (17.39%)	18
Neutropenia † 1	22/69 (31.88%)	43
Gastrointestinal disorders
Abdominal distension † 1	8/69 (11.59%)	9
Abdominal pain † 1	13/69 (18.84%)	14
Constipation † 1	24/69 (34.78%)	32
Diarrhoea † 1	16/69 (23.19%)	24
Dyspepsia † 1	4/69 (5.80%)	4
Nausea † 1	37/69 (53.62%)	89
Stomatitis † 1	4/69 (5.80%)	7
Vomiting † 1	26/69 (37.68%)	51
General disorders
Asthenia † 1	6/69 (8.70%)	6
Fatigue † 1	29/69 (42.03%)	52
Mucosal inflammation † 1	4/69 (5.80%)	6
Oedema † 1	5/69 (7.25%)	5
Investigations
Alanine aminotransferase increased † 1	6/69 (8.70%)	6
Aspartate aminotransferase increased † 1	8/69 (11.59%)	9
Blood alkaline phosphatase increased † 1	12/69 (17.39%)	17
Blood bilirubin increased † 1	4/69 (5.80%)	4
Blood creatinine increased † 1	7/69 (10.14%)	18
Creatinine renal clearance decreased † 1	4/69 (5.80%)	4
Haemoglobin decreased † 1	30/69 (43.48%)	45
Neutrophil count decreased † 1	26/69 (37.68%)	65
Platelet count decreased † 1	11/69 (15.94%)	21
Weight decreased † 1	10/69 (14.49%)	11
White blood cell count decreased † 1	18/69 (26.09%)	27
Metabolism and nutrition disorders
Anorexia † 1	27/69 (39.13%)	56
Decreased appetite † 1	6/69 (8.70%)	7
Diabetes mellitus † 1	4/69 (5.80%)	4
Hypercholesterolaemia † 1	5/69 (7.25%)	12
Hyperglycaemia † 1	14/69 (20.29%)	30
Hyperkalaemia † 1	11/69 (15.94%)	14
Hypocalcaemia † 1	9/69 (13.04%)	19
Hypokalaemia † 1	4/69 (5.80%)	7
Hypomagnesaemia † 1	5/69 (7.25%)	5
Hyponatraemia † 1	13/69 (18.84%)	15
Musculoskeletal and connective tissue disorders
Back pain † 1	7/69 (10.14%)	7
Myalgia † 1	6/69 (8.70%)	8
Nervous system disorders
Dizziness † 1	10/69 (14.49%)	19
Headache † 1	10/69 (14.49%)	14
Hypoaesthesia † 1	7/69 (10.14%)	7
Peripheral sensory neuropathy † 1	6/69 (8.70%)	6
Psychiatric disorders
Insomnia † 1	9/69 (13.04%)	9
Respiratory, thoracic and mediastinal disorders
Cough † 1	11/69 (15.94%)	13
Dyspnoea † 1	8/69 (11.59%)	8
Hiccups † 1	9/69 (13.04%)	10
Rhinorrhoea † 1	4/69 (5.80%)	4
Skin and subcutaneous tissue disorders
Pigmentation disorder † 1	10/69 (14.49%)	10
Pruritus † 1	7/69 (10.14%)	9
Rash † 1	7/69 (10.14%)	7
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 11.0

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

• Responsible Party: Chief Medical Officer, Eli Lilly
• ClinicalTrials.gov Identifier: NCT00320515
• Other Study ID Numbers: 7461; H3E-AA-S038
• First Submitted: April 28, 2006
• First Posted: May 3, 2006
• Results First Submitted: July 9, 2009
• Results First Posted: September 28, 2009
• Last Update Posted: September 28, 2009