A Study for Patients With Non-Squamous Non-Small Cell Lung Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00609518
• Collaborator: (none)
• Enrollment: 111
• Locations: 14
• Arms: 2
• Duration (Months): 28
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Chemotherapy for patients with non-squamous non-small cell lung cancer. Patients are given folic acid, vitamin B12 and steroids, both before and during treatment, to reduce the side effects associated with pemetrexed. The aim is whether it is possible to simplify the folic acid and steroid schedule without increasing toxicity.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: pemetrexed; Dietary Supplement: Folic acid; Dietary Supplement: Folic Acid; Dietary Supplement: Vitamin B12; Drug: dexamethasone; Drug: dexamethasone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 111 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pemetrexed With Simplified Folate and Dexamethasone Supplementation Versus Pemetrexed With Standard Supplementation as Second-line Chemotherapy for Patients With Non-squamous Non-small Cell Lung Cancer
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard Vitamin and Steroid Schedule + Pemetrexed Standard vitamin and steroid schedule that is used with pemetrexed consisting of a minimum of 5 daily doses of folic acid before first pemetrexed dose and dexamethasone on day before, day of, and day after treatment.	Drug: pemetrexed; 500 mg/m^2 intravenous infusion on day 1 of each 21-day cycle. Number of Cycles: Until progression or to a maximum of 6 cycles.; Other Names: Alimta LY231514 ; Dietary Supplement: Folic acid; 350-1000 micrograms taken orally for at least 5 daily doses during the 7-day period prior to the first dose of pemetrexed then continues daily throughout treatment until 3 weeks after the last dose of pemetrexed.; Other Names: Folate ; Dietary Supplement: Vitamin B12; 1000 micrograms intramuscular injection of vitamin B12 during the week prior to the first dose of pemetrexed then further injections given approximately every 9 weeks until 3 weeks after the last dose of pemetrexed.; Drug: dexamethasone; 4 mg taken orally [or equivalent] twice per day the day before, the day of, and the day after the first day of pemetrexed. Continue to give dexamethasone twice per day the day before, the day of, and the day after each dose of pemetrexed.
Experimental: Simplified Vitamin and Steroid Schedule + Pemetrexed Simplified vitamin and steroid schedule to be used with pemetrexed consisting of 2 daily doses of folic acid before first pemetrexed dose and dexamethasone on day of treatment only.	Drug: pemetrexed; 500 mg/m^2 intravenous infusion on day 1 of each 21-day cycle. Number of Cycles: Until progression or to a maximum of 6 cycles.; Other Names: Alimta LY231514 ; Dietary Supplement: Folic Acid; 350-1000 micrograms taken orally for two consecutive daily doses of folic acid the day before and the day of the first dose of pemetrexed the continues throughout treatment and for 3 weeks after the last dose of pemetrexed.; Other Names: Folate ; Dietary Supplement: Vitamin B12; 1000 micrograms intramuscular injection of vitamin B12 during the week prior to the first dose of pemetrexed then further injections given approximately every 9 weeks until 3 weeks after the last dose of pemetrexed.; Drug: dexamethasone; 4 mg taken orally [or equivalent] twice per day on the day of the first dose of pemetrexed. Continue to give dexamethasone twice per day on the day of each dose of pemetrexed.

Outcome Measures

Primary Outcome Measures

1. Safety: Number of Participants With Drug-Related Grade 3 or 4 Toxicity [From first dose of treatment to last dose of treatment plus 30 days]

   Results are presented for the number of participants with drug-related Grade 3 or 4 toxicity/adverse event (AE). Grades range from 0 (none) to 5 (death), with Grade 3 and 4 being defined as follows: Grade 0 = No AE; Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. A detailed list of Serious and non-serious adverse events is provided in the Reported Adverse Event section.

Secondary Outcome Measures

1. Proportion of Participants With Best Overall Tumor Response (Response Rate) [Baseline until disease progression, new therapy initiated, or death from any cause, up to 12 months after enrollment.]

   Response defined per Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=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. Best Overall Tumor Response is complete response plus partial response.

2. Overall Survival [Randomization (≤4 weeks from baseline visit) to 12 months after randomization]

   Overall survival is the duration from randomization to death. For patients who are alive, overall survival is censored at the date of last contact.

3. Progression-free Survival (PFS) [Randomization (≤4 weeks from baseline visit) to 12 months after randomization]

   Defined as the time from date of first dose to the first observation of disease progression, or death due to any cause. For patients who are alive and have not progressed, PFS is censored at the date of last radiological assessment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologic or cytologic diagnosis of non-small cell lung cancer (NSCLC) with locally advanced or metastatic disease (Stage IIIA, IIIB or IV)that is of non-squamous histology

• Patients must have failed only one prior chemotherapy regime and must be considered eligible for further chemotherapy following progression of their disease.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

• Adequate organ function

Exclusion Criteria:

• Concurrent administration of any other anti-tumor therapy

• Other co-existing malignancies

• Pregnancy or breast feeding

• Serious concomitant disorders

• Inability or unwillingness to take folic acid or vitamin B12 supplementation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bankstown	New South Wales	Australia	2200
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Concord	New South Wales	Australia	2139
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kingswood Penrith	New South Wales	Australia	2747
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Liverpool	New South Wales	Australia	2170
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Redcliffe	Queensland	Australia	4020
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bologna		Italy	40100
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Milano		Italy	20132
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Napoli		Italy	80100
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pisa		Italy	56100
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rome		Italy	00149
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mexico City		Mexico	14000
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Toluca		Mexico	CP50180
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pozuelo De Alarcon		Spain	28223
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sevilla		Spain	41014

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00609518
• Other Study ID Numbers: 11652; H3E-CR-S111
• First Posted: Feb 7, 2008
• Last Update Posted: Dec 28, 2010
• Last Verified: Dec 1, 2010

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Folic Acid; Vitamin B 12; Hydroxocobalamin; Vitamin B Complex; Dexamethasone; Dexamethasone acetate; Pemetrexed; BB 1101

Study Results

Participant Flow

Pre-assignment Detail	Completed is defined as:The patient has completed follow-up visits until 12 months after the randomization date. Qualified Intent-to-Treat (Q-ITT) is defined as: Include all randomized patients, with nonsquamous histology, who comply with their pretreatment folic acid and steroid supplementation schedule and take at least one dose of pemetrexed.

Arm/Group Title	Standard Vitamin and Steroid Schedule + Pemetrexed	Simplified Vitamin and Steroid Schedule + Pemetrexed
Arm/Group Description	Standard vitamin and steroid schedule that is used with pemetrexed consisting of a minimum of 5 daily doses of folic acid before first pemetrexed dose and dexamethasone on day before, day of, and day after treatment.	Simplified vitamin and steroid schedule to be used with pemetrexed consisting of 2 daily doses of folic acid before first pemetrexed dose and dexamethasone on day of treatment only.
Period Title: Overall Study
STARTED	54	57
Completed 6 Treatment Cycles	19	22
COMPLETED	11	17
NOT COMPLETED	43	40

Baseline Characteristics

Arm/Group Title	Standard Vitamin and Steroid Schedule + Pemetrexed	Simplified Vitamin and Steroid Schedule + Pemetrexed	Total
Arm/Group Description	Standard vitamin and steroid schedule that is used with pemetrexed consisting of a minimum of 5 daily doses of folic acid before first pemetrexed dose and dexamethasone on day before, day of, and day after treatment.	Simplified vitamin and steroid schedule to be used with pemetrexed consisting of 2 daily doses of folic acid before first pemetrexed dose and dexamethasone on day of treatment only.	Total of all reporting groups
Overall Participants	54	57	111
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.1 (11.08)	60.9 (12.13)	61.4 (11.60)
Sex: Female, Male (Count of Participants)
Female	22 40.7%	18 31.6%	40 36%
Male	32 59.3%	39 68.4%	71 64%
Region of Enrollment (participants) [Number]
Spain	8 14.8%	9 15.8%	17 15.3%
Mexico	27 50%	27 47.4%	54 48.6%
Italy	15 27.8%	18 31.6%	33 29.7%
Australia	4 7.4%	3 5.3%	7 6.3%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
0- Fully Active	26 48.1%	26 45.6%	52 46.8%
1- Ambulatory, Restricted Strenuous Activity	28 51.9%	28 49.1%	56 50.5%
2- Ambulatory, No Work Activities	0 0%	2 3.5%	2 1.8%
Not Assessed	0 0%	1 1.8%	1 0.9%
Smoking Status (Number) [Number]
Past Smoker	32 59.3%	33 57.9%	65 58.6%
Never Smoked	14 25.9%	15 26.3%	29 26.1%
Current Smoker	8 14.8%	9 15.8%	17 15.3%
Pathological Diagnosis (Number) [Number]
Cytological	17 31.5%	21 36.8%	38 34.2%
Histopathological	37 68.5%	36 63.2%	73 65.8%
Disease Stage (Number) [Number]
IIIA	3 5.6%	1 1.8%	4 3.6%
IIIB	9 16.7%	13 22.8%	22 19.8%
IV	42 77.8%	43 75.4%	85 76.6%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.3 (3.98)	26.0 (5.20)	25.7 (4.64)

Outcome Measures

1. Primary Outcome

Title	Safety: Number of Participants With Drug-Related Grade 3 or 4 Toxicity
Description	Results are presented for the number of participants with drug-related Grade 3 or 4 toxicity/adverse event (AE). Grades range from 0 (none) to 5 (death), with Grade 3 and 4 being defined as follows: Grade 0 = No AE; Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. A detailed list of Serious and non-serious adverse events is provided in the Reported Adverse Event section.
Time Frame	From first dose of treatment to last dose of treatment plus 30 days

Outcome Measure Data

Analysis Population Description

Qualified Intention to Treat (Q-ITT)

Arm/Group Title	Standard Vitamin and Steroid Schedule + Pemetrexed	Simplified Vitamin and Steroid Schedule + Pemetrexed
Arm/Group Description	Standard vitamin and steroid schedule that is used with pemetrexed consisting of a minimum of 5 daily doses of folic acid before first pemetrexed dose and dexamethasone on day before, day of, and day after treatment.	Simplified vitamin and steroid schedule to be used with pemetrexed consisting of 2 daily doses of folic acid before first pemetrexed dose and dexamethasone on day of treatment only.
Measure Participants	51	47
Number [participants]	15 27.8%	18 31.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Vitamin and Steroid Schedule + Pemetrexed, Simplified Vitamin and Steroid Schedule + Pemetrexed
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Proportion of Participants With Best Overall Tumor Response (Response Rate)
Description	Response defined per Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=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. Best Overall Tumor Response is complete response plus partial response.
Time Frame	Baseline until disease progression, new therapy initiated, or death from any cause, up to 12 months after enrollment.

Outcome Measure Data

Analysis Population Description

Qualified Intent to Treat (Q-ITT)

Arm/Group Title	Standard Vitamin and Steroid Schedule + Pemetrexed	Simplified Vitamin and Steroid Schedule + Pemetrexed
Arm/Group Description	Standard vitamin and steroid schedule that is used with pemetrexed consisting of a minimum of 5 daily doses of folic acid before first pemetrexed dose and dexamethasone on day before, day of, and day after treatment.	Simplified vitamin and steroid schedule to be used with pemetrexed consisting of 2 daily doses of folic acid before first pemetrexed dose and dexamethasone on day of treatment only.
Measure Participants	51	47
Mean (95% Confidence Interval) [proportion of patients]	0.118	0.064

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Vitamin and Steroid Schedule + Pemetrexed, Simplified Vitamin and Steroid Schedule + Pemetrexed
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4902
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival is the duration from randomization to death. For patients who are alive, overall survival is censored at the date of last contact.
Time Frame	Randomization (≤4 weeks from baseline visit) to 12 months after randomization

Outcome Measure Data

Analysis Population Description

Qualified Intent to Treat (Q-ITT)

Arm/Group Title	Standard Vitamin and Steroid Schedule + Pemetrexed	Simplified Vitamin and Steroid Schedule + Pemetrexed
Arm/Group Description	Standard vitamin and steroid schedule that is used with pemetrexed consisting of a minimum of 5 daily doses of folic acid before first pemetrexed dose and dexamethasone on day before, day of, and day after treatment.	Simplified vitamin and steroid schedule to be used with pemetrexed consisting of 2 daily doses of folic acid before first pemetrexed dose and dexamethasone on day of treatment only.
Measure Participants	51	47
Median (95% Confidence Interval) [months]	8.2	9.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Vitamin and Steroid Schedule + Pemetrexed, Simplified Vitamin and Steroid Schedule + Pemetrexed
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6791
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard Vitamin and Steroid Schedule + Pemetrexed, Simplified Vitamin and Steroid Schedule + Pemetrexed
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Defined as the time from date of first dose to the first observation of disease progression, or death due to any cause. For patients who are alive and have not progressed, PFS is censored at the date of last radiological assessment.
Time Frame	Randomization (≤4 weeks from baseline visit) to 12 months after randomization

Outcome Measure Data

Analysis Population Description

Qualified Intent to Treat (Q-ITT)

Arm/Group Title	Standard Vitamin and Steroid Schedule + Pemetrexed	Simplified Vitamin and Steroid Schedule + Pemetrexed
Arm/Group Description	Standard vitamin and steroid schedule that is used with pemetrexed consisting of a minimum of 5 daily doses of folic acid before first pemetrexed dose and dexamethasone on day before, day of, and day after treatment.	Simplified vitamin and steroid schedule to be used with pemetrexed consisting of 2 daily doses of folic acid before first pemetrexed dose and dexamethasone on day of treatment only.
Measure Participants	51	47
Median (95% Confidence Interval) [months]	3.7	3.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Vitamin and Steroid Schedule + Pemetrexed, Simplified Vitamin and Steroid Schedule + Pemetrexed
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5870
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard Vitamin and Steroid Schedule + Pemetrexed, Simplified Vitamin and Steroid Schedule + Pemetrexed
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.57 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Standard Vitamin and Steroid Schedule + Pemetrexed		Simplified Vitamin and Steroid Schedule + Pemetrexed
Arm/Group Description	Standard vitamin and steroid schedule that is used with pemetrexed consisting of a minimum of 5 daily doses of folic acid before first pemetrexed dose and dexamethasone on day before, day of, and day after treatment.		Simplified vitamin and steroid schedule to be used with pemetrexed consisting of 2 daily doses of folic acid before first pemetrexed dose and dexamethasone on day of treatment only.
All Cause Mortality
	Standard Vitamin and Steroid Schedule + Pemetrexed		Simplified Vitamin and Steroid Schedule + Pemetrexed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard Vitamin and Steroid Schedule + Pemetrexed		Simplified Vitamin and Steroid Schedule + Pemetrexed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/54 (33.3%)		18/57 (31.6%)
Blood and lymphatic system disorders
Anaemia	2/54 (3.7%)	2	1/57 (1.8%)	1
Febrile neutropenia	0/54 (0%)	0	2/57 (3.5%)	2
Leukopenia	0/54 (0%)	0	1/57 (1.8%)	1
Neutropenia	0/54 (0%)	0	1/57 (1.8%)	1
Pancytopenia	0/54 (0%)	0	1/57 (1.8%)	1
Thrombocytopenia	1/54 (1.9%)	1	0/57 (0%)	0
Cardiac disorders
Atrial fibrillation	1/54 (1.9%)	1	0/57 (0%)	0
Cardiac failure congestive	1/54 (1.9%)	1	0/57 (0%)	0
Sinus tachycardia	0/54 (0%)	0	1/57 (1.8%)	1
Gastrointestinal disorders
Constipation	1/54 (1.9%)	2	0/57 (0%)	0
Gastrointestinal inflammation	0/54 (0%)	0	1/57 (1.8%)	1
Nausea	0/54 (0%)	0	1/57 (1.8%)	1
Vomiting	0/54 (0%)	0	1/57 (1.8%)	1
General disorders
Chest pain	0/54 (0%)	0	2/57 (3.5%)	2
Oedema peripheral	1/54 (1.9%)	1	0/57 (0%)	0
Pyrexia	0/54 (0%)	0	1/57 (1.8%)	1
Infections and infestations
Bronchiectasis	0/54 (0%)	0	1/57 (1.8%)	1
Bronchitis	0/54 (0%)	0	1/57 (1.8%)	1
Cellulitis	1/54 (1.9%)	1	0/57 (0%)	0
Lobar pneumonia	0/54 (0%)	0	1/57 (1.8%)	1
Pneumonia	2/54 (3.7%)	2	1/57 (1.8%)	1
Respiratory tract infection	1/54 (1.9%)	1	0/57 (0%)	0
Urinary tract infection	0/54 (0%)	0	1/57 (1.8%)	1
Injury, poisoning and procedural complications
Humerus fracture	1/54 (1.9%)	1	0/57 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/54 (0%)	0	2/57 (3.5%)	2
Hyponatraemia	1/54 (1.9%)	1	0/57 (0%)	0
Musculoskeletal and connective tissue disorders
Bone pain	1/54 (1.9%)	1	1/57 (1.8%)	1
Muscular weakness	1/54 (1.9%)	1	0/57 (0%)	0
Pain in extremity	0/54 (0%)	0	1/57 (1.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion	0/54 (0%)	0	1/57 (1.8%)	1
Tumour pain	1/54 (1.9%)	1	0/57 (0%)	0
Nervous system disorders
Ataxia	0/54 (0%)	0	1/57 (1.8%)	1
Complex regional pain syndrome	0/54 (0%)	0	1/57 (1.8%)	1
Renal and urinary disorders
Renal failure	1/54 (1.9%)	1	1/57 (1.8%)	1
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/54 (0%)	0	1/57 (1.8%)	1
Dyspnoea	3/54 (5.6%)	3	1/57 (1.8%)	1
Hydropneumothorax	2/54 (3.7%)	2	0/57 (0%)	0
Hypoxia	1/54 (1.9%)	1	0/57 (0%)	0
Laryngeal oedema	1/54 (1.9%)	1	0/57 (0%)	0
Oesophagobronchial fistula	0/54 (0%)	0	1/57 (1.8%)	1
Pleural effusion	2/54 (3.7%)	2	2/57 (3.5%)	2
Pneumonitis	0/54 (0%)	0	1/57 (1.8%)	1
Pulmonary embolism	1/54 (1.9%)	1	1/57 (1.8%)	1
Respiratory failure	1/54 (1.9%)	1	1/57 (1.8%)	1
Skin and subcutaneous tissue disorders
Erythema multiforme	1/54 (1.9%)	1	1/57 (1.8%)	1
Swelling face	1/54 (1.9%)	1	0/57 (0%)	0
Other (Not Including Serious) Adverse Events
	Standard Vitamin and Steroid Schedule + Pemetrexed		Simplified Vitamin and Steroid Schedule + Pemetrexed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/54 (87%)		54/57 (94.7%)
Blood and lymphatic system disorders
Anaemia	13/54 (24.1%)	17	18/57 (31.6%)	24
Leukopenia	8/54 (14.8%)	13	18/57 (31.6%)	36
Lymphopenia	9/54 (16.7%)	9	15/57 (26.3%)	20
Neutropenia	13/54 (24.1%)	21	17/57 (29.8%)	31
Thrombocytopenia	7/54 (13%)	9	7/57 (12.3%)	8
Gastrointestinal disorders
Abdominal pain	3/54 (5.6%)	3	2/57 (3.5%)	2
Constipation	3/54 (5.6%)	3	4/57 (7%)	4
Diarrhoea	2/54 (3.7%)	2	4/57 (7%)	5
Nausea	11/54 (20.4%)	15	19/57 (33.3%)	21
Vomiting	6/54 (11.1%)	10	8/57 (14%)	8
General disorders
Asthenia	14/54 (25.9%)	16	14/57 (24.6%)	14
Chest pain	4/54 (7.4%)	4	2/57 (3.5%)	2
Fatigue	6/54 (11.1%)	7	7/57 (12.3%)	9
Pyrexia	0/54 (0%)	0	6/57 (10.5%)	9
Hepatobiliary disorders
Hyperbilirubinaemia	0/54 (0%)	0	3/57 (5.3%)	3
Investigations
Alanine aminotransferase increased	6/54 (11.1%)	10	9/57 (15.8%)	15
Aspartate aminotransferase increased	2/54 (3.7%)	4	6/57 (10.5%)	11
Blood alkaline phosphatase increased	3/54 (5.6%)	3	5/57 (8.8%)	7
Gamma-glutamyltransferase increased	0/54 (0%)	0	3/57 (5.3%)	3
Metabolism and nutrition disorders
Decreased appetite	1/54 (1.9%)	2	8/57 (14%)	8
Hyperglycaemia	4/54 (7.4%)	4	6/57 (10.5%)	7
Hyponatraemia	4/54 (7.4%)	5	8/57 (14%)	9
Musculoskeletal and connective tissue disorders
Back pain	0/54 (0%)	0	3/57 (5.3%)	3
Bone pain	1/54 (1.9%)	1	3/57 (5.3%)	3
Nervous system disorders
Headache	3/54 (5.6%)	3	1/57 (1.8%)	1
Respiratory, thoracic and mediastinal disorders
Cough	8/54 (14.8%)	9	11/57 (19.3%)	13
Dyspnoea	7/54 (13%)	8	11/57 (19.3%)	13
Skin and subcutaneous tissue disorders
Rash	8/54 (14.8%)	8	7/57 (12.3%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.