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Pemetrexed and Best Supportive Care Versus Placebo and Best Supportive Care in Non-Small Cell Lung Cancer (NSCLC)

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00102804
Collaborator
(none)
663
Enrollment
73
Locations
2
Arms
105
Duration (Months)
9.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a randomized Phase 3, double-blind study of maintenance pemetrexed plus best supportive care versus placebo plus best supportive care in NSCLC. Participants must have received 1 of 6 induction regimens for 4 cycles and did not have progressive disease prior to randomization (enrollment) into this trial.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
663 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Double-Blind, Placebo-Controlled Study of Maintenance Pemetrexed Plus Best Supportive Care Versus Best Supportive Care Immediately Following Induction Treatment for Advanced Non-Small Cell Lung Cancer
Study Start Date :
Mar 1, 2005
Actual Primary Completion Date :
Aug 1, 2007
Actual Study Completion Date :
Dec 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pemetrexed and Best Supportive Care

Drug: Pemetrexed
500 milligrams per square meter (mg/m^2), intravenous (IV) administration, every (q) 21 days, until disease progression
Other Names:
  • LY231514
  • Alimta

    • Other: Best Supportive Care
    Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
    Placebo Comparator: Placebo and Best Supportive Care

    Drug: Placebo
    IV administration, q 21 days

    Other: Best Supportive Care
    Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.

    Outcome Measures

    Primary Outcome Measures

    1. Progression-Free Survival (PFS) Time [Randomization to measured PD or death from any cause (up to 41 months)]

      PFS time was the elapsed time from the date of randomization to the first date of objective progression of disease or death from any cause. PFS was censored at the date of the participant's last tumor assessment for participants who were not known to have died or to have PD as of the data-inclusion cut-off date for analysis. PD, defined using Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0), was at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.

    Secondary Outcome Measures

    1. Overall Survival (OS) Time [Randomization to date of death from any cause (up to 41 months)]

      OS time was the elapsed time from the date of randomization to the date of death from any cause. OS was censored at the last date of contact for participants who were not known to have died as of the data-inclusion cut-off date for analysis.

    2. Time to Objective Progressive Disease (TPD) [Randomization to measured PD (up to 41 months)]

      TPD was the elapsed time from the date of randomization to the first date of objective PD. TPD was censored at the date of the participant's last tumor assessment for participants who were not known to have PD as of the data-inclusion cut-off date for analysis or who died without objective PD. PD, defined using RECIST v1.0, was at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.

    3. Time to Worsening of Symptoms (TWS) [Randomization to worsening of each LCSS item (up to 39 months)]

      TWS was the elapsed time from the date of randomization to the first date of worsening [defined as a 15-millimeter (mm) increase from baseline based on a 100-mm scale] of each symptom and summary item in the Lung Cancer Symptom Scale (LCSS). The participant-reported LCSS was a 9-item questionnaire. Six items were symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items described total symptomatic distress, interference with activity level, and global quality of life. Participant (pt) responses to each item were measured using visual analogue scales (VAS) from 0 (for best outcome) to 100 (for worst outcome). TWS was censored at the date of the last LCSS assessment for pts who were not known to have LCSS worsening.

    4. Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Tumor Response Rate) [Baseline to measured PD (up to 41 months)]

      Response was defined using RECIST v1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined either A) at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LDs or B) complete disappearance of target lesions, with persistence (but not worsening) of 1 or more nontarget lesions. In either case, no new lesions may have appeared. The percentage of participants with CR or PR=(Number of participants with CR or PR)/(Number of participants assessed)*100.

    5. Number of Participants With Adverse Events (AEs) [Baseline to study completion (up to 41 Months)]

      Clinically significant events were defined as serious adverse events (SAEs) and other non-serious AEs regardless of causality. A summary of serious and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

    6. Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS [Baseline through 30 days post discontinuation of study treatment (up to 39 Months)]

      The participant-reported LCSS was a 9-item questionnaire. Six items were symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items described total symptomatic distress, interference with activity level, and global quality of life. Participant responses to each item were measured using VAS from 0 (for best outcome) to 100 (for worst outcome). The average symptom burden index (ASBI) was the mean of the 6 symptom-specific items. The LCSS total score was the mean of the 9 items.

    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 NSCLC Stage IIIB (with pleural effusion and/or positive supraclavicular lymph nodes) or Stage IV prior to induction therapy.

    • Participants must have had 1 of the following induction therapies for treatment for Stage IIIB (with pleural effusion and/or positive supraclavicular lymph nodes) or IV NSCLC: Gemcitabine plus carboplatin, paclitaxel plus carboplatin, or docetaxel plus carboplatin, gemcitabine plus cisplatin, paclitaxel plus cisplatin or docetaxel plus cisplatin.

    • Participants must have received only 1 chemotherapeutic doublet lasting precisely 4 cycles.

    • Induction regimens must be based on 21-day cycles.

    • Documented evidence of a tumor response of complete response (CR), partial response (PR), or stable disease (SD). Tumor assessment must occur between Cycle 4 (Day 1) of induction therapy and the date of randomization. This response does not have to be confirmed in order for the participant to be randomized. Positron emission tomography (PET) scans and ultrasounds may not be used for lesion measurements for response determination.

    Exclusion Criteria:

    • With the exception of those chemotherapies listed as inclusion criterion, participants will not be included if they have received prior systemic anticancer therapy (including adjuvant early-stage treatment for NSCLC) or any systemic treatment for any other cancer.

    • Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.

    • Inability to comply with protocol or study procedures.

    • A serious concomitant systemic disorder that would compromise the participant's ability to complete the study.

    • A serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV.

    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. Minneapolis Minnesota United States 55455
    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. Portsmouth New Hampshire United States 03801
    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. Pittsburgh Pennsylvania United States 15213
    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. Memphis Tennessee United States 38120
    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. Dallas Texas United States 75204
    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. Marshfield Wisconsin United States 54449
    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. Bankstown New South Wales Australia 2200
    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. Coffs Harbour New South Wales Australia 2450
    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. Kogarah New South Wales Australia 2217
    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. Port Macquarie New South Wales Australia 2444
    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. Nambour Queensland Australia 4560
    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. Townsville Queensland Australia 4810
    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. Ashford South Australia Australia 5035
    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. Frankston Victoria Australia VIC 3199
    15 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. Vienna Austria 1130
    16 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. Ijui Brazil 98700 000
    17 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. Sao Paulo Brazil 01277-900
    18 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. Sofia Bulgaria 1527
    19 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. Varna Bulgaria 9010
    20 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. Beijing China 100730
    21 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. Dalian China 116023
    22 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. Guang Zhou China 510080
    23 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. Hangzhou China 310016
    24 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. Ji Nan China 250012
    25 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. Nan Jing China 210009
    26 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. Shanghai China 200025
    27 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. Zagreb Croatia 10000
    28 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. Brno Czech Republic 656 91
    29 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. Ostrava-Poruba Czech Republic 708 52
    30 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. Prague Czech Republic 128 08
    31 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. Hamburg Germany D-20246
    32 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. Hamm Germany 59071
    33 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. Hannover Germany D-30625
    34 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. Magdeburg Germany D-39120
    35 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. Ulm Germany D-89081
    36 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. Athens Greece 11527
    37 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. Chania Greece 73300
    38 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. Mosdos Hungary 7257
    39 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. Szombathely Hungary H-9700
    40 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. Banglagore India 560034
    41 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. Jaipur India 302017
    42 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. Mumbai India 400 026
    43 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. P.O Ernakulam India 682304
    44 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. Trivandrum India 695 011
    45 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. Bari Italy 70126
    46 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
    47 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. Genova Italy 16132
    48 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. Livorno Italy 57128
    49 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. Messina Italy 98122
    50 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. Padova Italy 35128
    51 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
    52 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 00168
    53 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. Rozzano Italy 20089
    54 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. Seoul Korea, Republic of 139-706
    55 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. Amsterdam Netherlands 1105 AZ
    56 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. Ede Netherlands 6716 RP
    57 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. Zutphen Netherlands 7207 BA
    58 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. Zwolle Netherlands 80211 JW
    59 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. Poznan Poland 60-569
    60 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. Warsaw Poland 02-781
    61 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. Cluj-Napoca Romania 3400
    62 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. Oradea Romania 3700
    63 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. Alcoi Spain 03804
    64 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. Alcorcon Spain 28922
    65 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. Barcelona Spain 08003
    66 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. Granada Spain 18014
    67 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. Mataró Spain 08304
    68 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. Murcia Spain 30008
    69 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. Palma De Mallorca Spain 07198
    70 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. Santa Cruz De Tenerife Spain 38320
    71 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. Taipei Taiwan 112
    72 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. Ankara Turkey 06100
    73 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. Izmir Turkey 35100

    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:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT00102804
    Other Study ID Numbers:
    • 5122
    • H3E-MC-JMEN
    First Posted:
    Feb 2, 2005
    Last Update Posted:
    Dec 29, 2014
    Last Verified:
    Dec 1, 2014
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Pemetrexed

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Participants who signed the informed consent form (ICF) and completed the randomized process are presented in the participant flow by the treatment arm to which they were randomized. Participants who did not sign the ICF or complete the randomization process were removed from the database and excluded from all analyses.
    Arm/Group Title Pemetrexed and BSC Placebo and BSC
    Arm/Group Description Pemetrexed: 500 milligrams per square meter (mg/m^2), intravenous (IV) administration, every (q) 21 days, until disease progression. Best Supportive Care (BSC): Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician. Placebo: IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
    Period Title: Overall Study
    STARTED 441 222
    Received at Least 1 Dose of Study Drug 434 222
    COMPLETED 0 0
    NOT COMPLETED 441 222

    Baseline Characteristics

    Arm/Group Title Pemetrexed and BSC Placebo and BSC Total
    Arm/Group Description Pemetrexed: 500 mg/m^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician. Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician. Total of all reporting groups
    Overall Participants 441 222 663
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    60.6
    60.4
    60.6
    Sex: Female, Male (Count of Participants)
    Female
    119
    27%
    61
    27.5%
    180
    27.1%
    Male
    322
    73%
    161
    72.5%
    483
    72.9%
    Race/Ethnicity, Customized (participants) [Number]
    Aboriginal
    0
    0%
    1
    0.5%
    1
    0.2%
    African
    6
    1.4%
    0
    0%
    6
    0.9%
    Caucasian
    279
    63.3%
    149
    67.1%
    428
    64.6%
    East Asian
    104
    23.6%
    50
    22.5%
    154
    23.2%
    Hispanic
    13
    2.9%
    6
    2.7%
    19
    2.9%
    West Asian
    39
    8.8%
    16
    7.2%
    55
    8.3%
    Region of Enrollment (participants) [Number]
    United States
    20
    4.5%
    12
    5.4%
    32
    4.8%
    Taiwan
    5
    1.1%
    4
    1.8%
    9
    1.4%
    Greece
    18
    4.1%
    9
    4.1%
    27
    4.1%
    Spain
    30
    6.8%
    19
    8.6%
    49
    7.4%
    Turkey
    7
    1.6%
    4
    1.8%
    11
    1.7%
    Austria
    2
    0.5%
    2
    0.9%
    4
    0.6%
    Italy
    18
    4.1%
    16
    7.2%
    34
    5.1%
    India
    39
    8.8%
    16
    7.2%
    55
    8.3%
    Hungary
    8
    1.8%
    6
    2.7%
    14
    2.1%
    Czech Republic
    5
    1.1%
    2
    0.9%
    7
    1.1%
    Poland
    25
    5.7%
    11
    5%
    36
    5.4%
    Brazil
    24
    5.4%
    10
    4.5%
    34
    5.1%
    Croatia
    10
    2.3%
    3
    1.4%
    13
    2%
    Romania
    51
    11.6%
    26
    11.7%
    77
    11.6%
    Australia
    19
    4.3%
    8
    3.6%
    27
    4.1%
    Bulgaria
    11
    2.5%
    8
    3.6%
    19
    2.9%
    Netherlands
    10
    2.3%
    4
    1.8%
    14
    2.1%
    Germany
    40
    9.1%
    16
    7.2%
    56
    8.4%
    China
    62
    14.1%
    37
    16.7%
    99
    14.9%
    Korea, Republic of
    37
    8.4%
    9
    4.1%
    46
    6.9%

    Outcome Measures

    1. Primary Outcome
    Title Progression-Free Survival (PFS) Time
    Description PFS time was the elapsed time from the date of randomization to the first date of objective progression of disease or death from any cause. PFS was censored at the date of the participant's last tumor assessment for participants who were not known to have died or to have PD as of the data-inclusion cut-off date for analysis. PD, defined using Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0), was at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
    Time Frame Randomization to measured PD or death from any cause (up to 41 months)

    Outcome Measure Data

    Analysis Population Description
    Participants who signed the ICF and completed the randomized process are reported according to the treatment arm to which they were randomized. Participants censored: N = 123, 36 participants in the pemetrexed and placebo treatment arms, respectively.
    Arm/Group Title Pemetrexed and BSC Placebo and BSC
    Arm/Group Description Pemetrexed: 500 mg/m^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician. Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
    Measure Participants 441 222
    Median (95% Confidence Interval) [months]
    4.27
    2.60
    2. Secondary Outcome
    Title Overall Survival (OS) Time
    Description OS time was the elapsed time from the date of randomization to the date of death from any cause. OS was censored at the last date of contact for participants who were not known to have died as of the data-inclusion cut-off date for analysis.
    Time Frame Randomization to date of death from any cause (up to 41 months)

    Outcome Measure Data

    Analysis Population Description
    Participants who signed the ICF and completed the randomized process are reported according to the treatment arm to which they were randomized. Participants censored: N = 138, 48 participants in the pemetrexed and placebo treatment arms, respectively.
    Arm/Group Title Pemetrexed and BSC Placebo and BSC
    Arm/Group Description Pemetrexed: 500 mg/m^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician. Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
    Measure Participants 441 222
    Median (95% Confidence Interval) [months]
    13.37
    10.58
    3. Secondary Outcome
    Title Time to Objective Progressive Disease (TPD)
    Description TPD was the elapsed time from the date of randomization to the first date of objective PD. TPD was censored at the date of the participant's last tumor assessment for participants who were not known to have PD as of the data-inclusion cut-off date for analysis or who died without objective PD. PD, defined using RECIST v1.0, was at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
    Time Frame Randomization to measured PD (up to 41 months)

    Outcome Measure Data

    Analysis Population Description
    Participants who signed the ICF and completed the randomized process are reported according to the treatment arm to which they were randomized. Participants censored: N = 145, 40 participants in the pemetrexed and placebo treatment arms, respectively.
    Arm/Group Title Pemetrexed and BSC Placebo and BSC
    Arm/Group Description Pemetrexed: 500 mg/m^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician. Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
    Measure Participants 441 222
    Median (95% Confidence Interval) [months]
    4.27
    2.60
    4. Secondary Outcome
    Title Time to Worsening of Symptoms (TWS)
    Description TWS was the elapsed time from the date of randomization to the first date of worsening [defined as a 15-millimeter (mm) increase from baseline based on a 100-mm scale] of each symptom and summary item in the Lung Cancer Symptom Scale (LCSS). The participant-reported LCSS was a 9-item questionnaire. Six items were symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items described total symptomatic distress, interference with activity level, and global quality of life. Participant (pt) responses to each item were measured using visual analogue scales (VAS) from 0 (for best outcome) to 100 (for worst outcome). TWS was censored at the date of the last LCSS assessment for pts who were not known to have LCSS worsening.
    Time Frame Randomization to worsening of each LCSS item (up to 39 months)

    Outcome Measure Data

    Analysis Population Description
    Pts who signed ICF and completed randomization, according to treatment randomized. Pts censored: Loss of appetite 236,140; fatigue 237,130; cough 274,146; dyspnea 271,143, hemoptysis 404,198; pain 271,135; symptom distress 247,141; interference with activity level 267,141, global quality of life 262,137 pts in pemetrexed, placebo arm, respectively.
    Arm/Group Title Pemetrexed and BSC Placebo and BSC
    Arm/Group Description Pemetrexed: 500 mg/m^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician. Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
    Measure Participants 441 222
    Loss of appetite
    3.78
    4.40
    Fatigue
    3.06
    3.09
    Cough
    6.05
    4.67
    Dyspnea
    5.36
    4.40
    Hemoptysis
    NA
    NA
    Pain
    6.11
    4.63
    Symptomatic distress
    4.21
    3.78
    Interference with activity level
    6.51
    3.98
    Global quality of life
    5.75
    3.71
    5. Secondary Outcome
    Title Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Tumor Response Rate)
    Description Response was defined using RECIST v1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined either A) at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LDs or B) complete disappearance of target lesions, with persistence (but not worsening) of 1 or more nontarget lesions. In either case, no new lesions may have appeared. The percentage of participants with CR or PR=(Number of participants with CR or PR)/(Number of participants assessed)*100.
    Time Frame Baseline to measured PD (up to 41 months)

    Outcome Measure Data

    Analysis Population Description
    Participants who signed the ICF and completed the randomized process are reported according to the treatment arm to which they were randomized.
    Arm/Group Title Pemetrexed and BSC Placebo and BSC
    Arm/Group Description Pemetrexed: 500 mg/m^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician. Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
    Measure Participants 441 222
    Number (95% Confidence Interval) [percentage of participants]
    6.8
    1.5%
    1.8
    0.8%
    6. Secondary Outcome
    Title Number of Participants With Adverse Events (AEs)
    Description Clinically significant events were defined as serious adverse events (SAEs) and other non-serious AEs regardless of causality. A summary of serious and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
    Time Frame Baseline to study completion (up to 41 Months)

    Outcome Measure Data

    Analysis Population Description
    Participants who signed the ICF, completed the randomized process and received at least 1 dose of study drug are reported according to the treatment to which they were received.
    Arm/Group Title Pemetrexed and BSC Placebo and BSC
    Arm/Group Description Pemetrexed: 500 mg/m^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician. Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
    Measure Participants 438 218
    SAEs
    83
    18.8%
    31
    14%
    Other Non-Serious AEs
    386
    87.5%
    178
    80.2%
    7. Secondary Outcome
    Title Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS
    Description The participant-reported LCSS was a 9-item questionnaire. Six items were symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items described total symptomatic distress, interference with activity level, and global quality of life. Participant responses to each item were measured using VAS from 0 (for best outcome) to 100 (for worst outcome). The average symptom burden index (ASBI) was the mean of the 6 symptom-specific items. The LCSS total score was the mean of the 9 items.
    Time Frame Baseline through 30 days post discontinuation of study treatment (up to 39 Months)

    Outcome Measure Data

    Analysis Population Description
    Participants who signed the ICF, completed the randomization process, had LCSS data at baseline and at least once postdose are reported according to the treatment arm to which they were randomized.
    Arm/Group Title Pemetrexed and BSC Placebo and BSC
    Arm/Group Description Pemetrexed: 500 mg/m^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician. Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
    Measure Participants 403 197
    Loss of appetite (n=403, 197)
    7.3
    (25.90)
    10.6
    (25.25)
    Fatigue (n=403, 197)
    10.2
    (27.10)
    10.4
    (23.92)
    Cough (n=402, 197)
    7.6
    (20.09)
    6.7
    (23.81)
    Dyspnea (n=400, 196)
    7.6
    (22.50)
    5.4
    (20.44)
    Pain (n=401, 197)
    5.4
    (20.96)
    4.3
    (21.93)
    Hemoptysis (n=402, 196)
    1.5
    (9.41)
    2.1
    (9.23)
    Symptom distress (n=401, 196)
    6.5
    (21.13)
    8.2
    (22.5)
    Interference with activity level (n=400, 197)
    10.8
    (27.08)
    9.3
    (25.50)
    Global quality of life (n=401, 195)
    10.7
    (24.94)
    10.5
    (22.98)
    ASBI (n=392, 195)
    3.7
    (12.34)
    3.8
    (13.24)
    Total LCSS (n=388, 193)
    4.07
    (12.76)
    4.04
    (13.03)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description Participants are reported under the treatment to which they received.
    Arm/Group Title Pemetrexed and BSC Placebo and BSC
    Arm/Group Description Pemetrexed: 500 mg/m^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician. Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
    All Cause Mortality
    Pemetrexed and BSC Placebo and BSC
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Pemetrexed and BSC Placebo and BSC
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 83/438 (18.9%) 31/218 (14.2%)
    Blood and lymphatic system disorders
    Anaemia 6/438 (1.4%) 7 0/218 (0%) 0
    Anaemia of malignant disease 0/438 (0%) 0 1/218 (0.5%) 1
    Febrile neutropenia 4/438 (0.9%) 4 0/218 (0%) 0
    Leukopenia 1/438 (0.2%) 1 0/218 (0%) 0
    Neutropenia 2/438 (0.5%) 2 1/218 (0.5%) 1
    Thrombocytopenia 3/438 (0.7%) 3 0/218 (0%) 0
    Cardiac disorders
    Acute myocardial infarction 1/438 (0.2%) 1 0/218 (0%) 0
    Atrial fibrillation 1/438 (0.2%) 1 0/218 (0%) 0
    Cardiac failure 0/438 (0%) 0 1/218 (0.5%) 1
    Cardio-respiratory arrest 1/438 (0.2%) 1 0/218 (0%) 0
    Myocardial infarction 1/438 (0.2%) 1 0/218 (0%) 0
    Myocardial ischaemia 1/438 (0.2%) 1 0/218 (0%) 0
    Pericardial effusion 1/438 (0.2%) 1 0/218 (0%) 0
    Sinus tachycardia 1/438 (0.2%) 1 0/218 (0%) 0
    Ear and labyrinth disorders
    Vertigo 0/438 (0%) 0 1/218 (0.5%) 1
    Gastrointestinal disorders
    Abdominal pain 1/438 (0.2%) 1 1/218 (0.5%) 1
    Constipation 1/438 (0.2%) 1 0/218 (0%) 0
    Dysphagia 2/438 (0.5%) 2 0/218 (0%) 0
    Haematemesis 1/438 (0.2%) 1 0/218 (0%) 0
    Large intestine perforation 1/438 (0.2%) 1 0/218 (0%) 0
    Nausea 1/438 (0.2%) 1 1/218 (0.5%) 1
    Reflux oesophagitis 1/438 (0.2%) 2 0/218 (0%) 0
    Vomiting 0/438 (0%) 0 2/218 (0.9%) 2
    General disorders
    Asthenia 4/438 (0.9%) 4 0/218 (0%) 0
    Chest pain 3/438 (0.7%) 3 0/218 (0%) 0
    Death 0/438 (0%) 0 1/218 (0.5%) 1
    Fatigue 3/438 (0.7%) 3 0/218 (0%) 0
    General physical health deterioration 3/438 (0.7%) 3 0/218 (0%) 0
    Mucosal inflammation 2/438 (0.5%) 2 0/218 (0%) 0
    Multi-organ failure 1/438 (0.2%) 1 0/218 (0%) 0
    Pain 0/438 (0%) 0 1/218 (0.5%) 1
    Performance status decreased 1/438 (0.2%) 1 0/218 (0%) 0
    Pyrexia 4/438 (0.9%) 5 1/218 (0.5%) 1
    Infections and infestations
    Bronchitis 2/438 (0.5%) 2 1/218 (0.5%) 1
    Bronchopneumonia 0/438 (0%) 0 1/218 (0.5%) 1
    Cellulitis 2/438 (0.5%) 2 0/218 (0%) 0
    Erysipelas 1/438 (0.2%) 1 0/218 (0%) 0
    Gastrointestinal infection 1/438 (0.2%) 1 0/218 (0%) 0
    Herpes zoster 1/438 (0.2%) 1 0/218 (0%) 0
    Infection 1/438 (0.2%) 1 0/218 (0%) 0
    Oral candidiasis 1/438 (0.2%) 1 0/218 (0%) 0
    Pneumonia 10/438 (2.3%) 10 3/218 (1.4%) 3
    Pulmonary sepsis 1/438 (0.2%) 1 0/218 (0%) 0
    Respiratory tract infection 1/438 (0.2%) 1 1/218 (0.5%) 1
    Sepsis 1/438 (0.2%) 1 0/218 (0%) 0
    Skin infection 0/438 (0%) 0 1/218 (0.5%) 1
    Urinary tract infection 3/438 (0.7%) 3 1/218 (0.5%) 1
    Urosepsis 1/438 (0.2%) 1 0/218 (0%) 0
    Viral upper respiratory tract infection 0/438 (0%) 0 1/218 (0.5%) 1
    Injury, poisoning and procedural complications
    Femur fracture 1/438 (0.2%) 1 0/218 (0%) 0
    Rib fracture 1/438 (0.2%) 1 0/218 (0%) 0
    Investigations
    Weight decreased 1/438 (0.2%) 1 0/218 (0%) 0
    Metabolism and nutrition disorders
    Anorexia 4/438 (0.9%) 5 0/218 (0%) 0
    Dehydration 1/438 (0.2%) 2 0/218 (0%) 0
    Diabetic ketoacidosis 1/438 (0.2%) 1 0/218 (0%) 0
    Hypercalcaemia 1/438 (0.2%) 1 0/218 (0%) 0
    Hypercholesterolaemia 0/438 (0%) 0 1/218 (0.5%) 1
    Hypoglycaemia 1/438 (0.2%) 1 0/218 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/438 (0%) 0 1/218 (0.5%) 1
    Back pain 0/438 (0%) 0 1/218 (0.5%) 1
    Bone pain 0/438 (0%) 0 1/218 (0.5%) 1
    Intervertebral disc degeneration 1/438 (0.2%) 1 0/218 (0%) 0
    Joint effusion 1/438 (0.2%) 1 0/218 (0%) 0
    Muscle contracture 0/438 (0%) 0 1/218 (0.5%) 1
    Muscular weakness 0/438 (0%) 0 1/218 (0.5%) 1
    Myalgia 1/438 (0.2%) 1 0/218 (0%) 0
    Pain in extremity 1/438 (0.2%) 1 0/218 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Meningioma 1/438 (0.2%) 1 0/218 (0%) 0
    Metastases to central nervous system 1/438 (0.2%) 1 0/218 (0%) 0
    Tumour pain 0/438 (0%) 0 1/218 (0.5%) 1
    Nervous system disorders
    Convulsion 1/438 (0.2%) 1 0/218 (0%) 0
    Dizziness 0/438 (0%) 0 2/218 (0.9%) 2
    Epilepsy 0/438 (0%) 0 1/218 (0.5%) 1
    Headache 1/438 (0.2%) 1 1/218 (0.5%) 2
    Hemiparesis 1/438 (0.2%) 1 0/218 (0%) 0
    Hypoaesthesia 0/438 (0%) 0 1/218 (0.5%) 1
    Ischaemic stroke 1/438 (0.2%) 1 0/218 (0%) 0
    Paraparesis 1/438 (0.2%) 1 0/218 (0%) 0
    Paraplegia 1/438 (0.2%) 1 0/218 (0%) 0
    Partial seizures 1/438 (0.2%) 1 0/218 (0%) 0
    Spinal cord compression 1/438 (0.2%) 1 0/218 (0%) 0
    Transient ischaemic attack 1/438 (0.2%) 1 0/218 (0%) 0
    Psychiatric disorders
    Confusional state 1/438 (0.2%) 1 1/218 (0.5%) 1
    Renal and urinary disorders
    Dysuria 1/438 (0.2%) 1 1/218 (0.5%) 1
    Nephrolithiasis 1/438 (0.2%) 1 0/218 (0%) 0
    Renal failure 1/438 (0.2%) 1 0/218 (0%) 0
    Renal failure acute 1/438 (0.2%) 1 0/218 (0%) 0
    Urinary retention 1/438 (0.2%) 1 1/218 (0.5%) 1
    Reproductive system and breast disorders
    Balanitis 1/321 (0.3%) 1 0/158 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 1/438 (0.2%) 1 0/218 (0%) 0
    Bronchial obstruction 0/438 (0%) 0 1/218 (0.5%) 1
    Cough 1/438 (0.2%) 1 1/218 (0.5%) 1
    Dyspnoea 14/438 (3.2%) 14 6/218 (2.8%) 6
    Haemoptysis 1/438 (0.2%) 1 1/218 (0.5%) 1
    Hypoxia 1/438 (0.2%) 1 0/218 (0%) 0
    Pleural effusion 1/438 (0.2%) 1 1/218 (0.5%) 1
    Pneumonia aspiration 1/438 (0.2%) 1 0/218 (0%) 0
    Pneumonitis 0/438 (0%) 0 1/218 (0.5%) 1
    Pulmonary embolism 1/438 (0.2%) 1 0/218 (0%) 0
    Pulmonary fibrosis 1/438 (0.2%) 1 0/218 (0%) 0
    Respiratory failure 4/438 (0.9%) 4 0/218 (0%) 0
    Vascular disorders
    Deep vein thrombosis 2/438 (0.5%) 2 0/218 (0%) 0
    Pelvic venous thrombosis 1/438 (0.2%) 1 0/218 (0%) 0
    Superior vena caval occlusion 1/438 (0.2%) 1 0/218 (0%) 0
    Other (Not Including Serious) Adverse Events
    Pemetrexed and BSC Placebo and BSC
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 386/438 (88.1%) 178/218 (81.7%)
    Blood and lymphatic system disorders
    Anaemia 65/438 (14.8%) 97 12/218 (5.5%) 15
    Anaemia of malignant disease 1/438 (0.2%) 1 0/218 (0%) 0
    Febrile neutropenia 1/438 (0.2%) 1 0/218 (0%) 0
    Leukocytosis 0/438 (0%) 0 1/218 (0.5%) 1
    Leukopenia 25/438 (5.7%) 64 5/218 (2.3%) 8
    Lymph node pain 0/438 (0%) 0 1/218 (0.5%) 1
    Lymphadenopathy 3/438 (0.7%) 4 0/218 (0%) 0
    Lymphopenia 3/438 (0.7%) 3 1/218 (0.5%) 1
    Neutropenia 21/438 (4.8%) 66 5/218 (2.3%) 5
    Neutrophilia 2/438 (0.5%) 2 0/218 (0%) 0
    Thrombocythaemia 1/438 (0.2%) 1 0/218 (0%) 0
    Thrombocytopenia 17/438 (3.9%) 29 2/218 (0.9%) 3
    Cardiac disorders
    Arrhythmia 1/438 (0.2%) 1 1/218 (0.5%) 1
    Arrhythmia supraventricular 0/438 (0%) 0 1/218 (0.5%) 1
    Atrial fibrillation 2/438 (0.5%) 2 0/218 (0%) 0
    Atrial tachycardia 1/438 (0.2%) 1 1/218 (0.5%) 1
    Bradycardia 1/438 (0.2%) 1 0/218 (0%) 0
    Cyanosis 1/438 (0.2%) 1 0/218 (0%) 0
    Myocardial ischaemia 0/438 (0%) 0 1/218 (0.5%) 1
    Palpitations 1/438 (0.2%) 2 3/218 (1.4%) 3
    Pericardial effusion 1/438 (0.2%) 1 0/218 (0%) 0
    Sinus tachycardia 1/438 (0.2%) 1 1/218 (0.5%) 1
    Tachycardia 3/438 (0.7%) 4 1/218 (0.5%) 1
    Ear and labyrinth disorders
    Cerumen impaction 1/438 (0.2%) 1 0/218 (0%) 0
    Deafness 2/438 (0.5%) 3 0/218 (0%) 0
    Ear discomfort 1/438 (0.2%) 1 0/218 (0%) 0
    Ear pain 1/438 (0.2%) 1 0/218 (0%) 0
    Hypoacusis 1/438 (0.2%) 1 0/218 (0%) 0
    Motion sickness 1/438 (0.2%) 1 0/218 (0%) 0
    Tinnitus 5/438 (1.1%) 5 1/218 (0.5%) 1
    Vertigo 2/438 (0.5%) 2 1/218 (0.5%) 1
    Endocrine disorders
    Goitre 1/438 (0.2%) 1 0/218 (0%) 0
    Hyperthyroidism 1/438 (0.2%) 1 0/218 (0%) 0
    Hypothyroidism 1/438 (0.2%) 1 0/218 (0%) 0
    Eye disorders
    Blepharitis 1/438 (0.2%) 1 0/218 (0%) 0
    Cataract 2/438 (0.5%) 2 1/218 (0.5%) 1
    Conjunctivitis 20/438 (4.6%) 24 1/218 (0.5%) 1
    Conjunctivitis allergic 1/438 (0.2%) 1 0/218 (0%) 0
    Dry eye 1/438 (0.2%) 1 1/218 (0.5%) 1
    Eye pain 2/438 (0.5%) 2 0/218 (0%) 0
    Eye swelling 2/438 (0.5%) 2 0/218 (0%) 0
    Eyelid oedema 3/438 (0.7%) 3 0/218 (0%) 0
    Keratoconjunctivitis sicca 4/438 (0.9%) 4 0/218 (0%) 0
    Lacrimation increased 20/438 (4.6%) 21 0/218 (0%) 0
    Ocular surface disease 3/438 (0.7%) 5 1/218 (0.5%) 2
    Photophobia 2/438 (0.5%) 2 0/218 (0%) 0
    Pterygium 1/438 (0.2%) 1 0/218 (0%) 0
    Vision blurred 8/438 (1.8%) 10 1/218 (0.5%) 1
    Visual acuity reduced 1/438 (0.2%) 1 1/218 (0.5%) 1
    Visual disturbance 1/438 (0.2%) 1 0/218 (0%) 0
    Gastrointestinal disorders
    Abdominal distension 4/438 (0.9%) 4 2/218 (0.9%) 2
    Abdominal pain 18/438 (4.1%) 18 8/218 (3.7%) 8
    Abdominal pain lower 1/438 (0.2%) 1 0/218 (0%) 0
    Abdominal pain upper 7/438 (1.6%) 7 3/218 (1.4%) 11
    Aphthous stomatitis 0/438 (0%) 0 1/218 (0.5%) 1
    Ascites 1/438 (0.2%) 1 0/218 (0%) 0
    Constipation 59/438 (13.5%) 85 17/218 (7.8%) 22
    Dental caries 2/438 (0.5%) 2 0/218 (0%) 0
    Diarrhoea 52/438 (11.9%) 88 15/218 (6.9%) 17
    Dry mouth 10/438 (2.3%) 10 3/218 (1.4%) 3
    Dyspepsia 13/438 (3%) 18 6/218 (2.8%) 21
    Dysphagia 4/438 (0.9%) 5 1/218 (0.5%) 2
    Faecal incontinence 1/438 (0.2%) 1 0/218 (0%) 0
    Faecaloma 0/438 (0%) 0 2/218 (0.9%) 2
    Flatulence 4/438 (0.9%) 7 0/218 (0%) 0
    Gastric disorder 1/438 (0.2%) 1 0/218 (0%) 0
    Gastritis 4/438 (0.9%) 5 1/218 (0.5%) 1
    Gastrointestinal pain 0/438 (0%) 0 1/218 (0.5%) 1
    Gastrooesophageal reflux disease 1/438 (0.2%) 1 2/218 (0.9%) 2
    Gingival pain 2/438 (0.5%) 2 0/218 (0%) 0
    Gingivitis 1/438 (0.2%) 1 1/218 (0.5%) 1
    Haemorrhoids 1/438 (0.2%) 1 0/218 (0%) 0
    Hiatus hernia 1/438 (0.2%) 1 0/218 (0%) 0
    Ileus 1/438 (0.2%) 1 0/218 (0%) 0
    Inflammatory bowel disease 0/438 (0%) 0 1/218 (0.5%) 1
    Lip ulceration 1/438 (0.2%) 1 0/218 (0%) 0
    Mouth ulceration 3/438 (0.7%) 3 0/218 (0%) 0
    Nausea 102/438 (23.3%) 209 22/218 (10.1%) 24
    Odynophagia 4/438 (0.9%) 5 1/218 (0.5%) 1
    Oesophageal haemorrhage 1/438 (0.2%) 1 0/218 (0%) 0
    Oesophagitis 2/438 (0.5%) 2 0/218 (0%) 0
    Oral pain 2/438 (0.5%) 2 1/218 (0.5%) 1
    Paraesthesia oral 2/438 (0.5%) 4 0/218 (0%) 0
    Periodontal disease 2/438 (0.5%) 2 0/218 (0%) 0
    Rectal haemorrhage 1/438 (0.2%) 1 1/218 (0.5%) 1
    Stomatitis 19/438 (4.3%) 22 1/218 (0.5%) 1
    Tongue black hairy 1/438 (0.2%) 1 0/218 (0%) 0
    Tongue coated 1/438 (0.2%) 1 0/218 (0%) 0
    Toothache 4/438 (0.9%) 4 0/218 (0%) 0
    Vomiting 56/438 (12.8%) 88 9/218 (4.1%) 12
    General disorders
    Asthenia 48/438 (11%) 74 10/218 (4.6%) 11
    Axillary pain 2/438 (0.5%) 2 0/218 (0%) 0
    Catheter site erythema 1/438 (0.2%) 1 0/218 (0%) 0
    Chest discomfort 3/438 (0.7%) 14 0/218 (0%) 0
    Chest pain 44/438 (10%) 67 16/218 (7.3%) 17
    Chills 7/438 (1.6%) 9 0/218 (0%) 0
    Condition aggravated 1/438 (0.2%) 1 0/218 (0%) 0
    Cyst 0/438 (0%) 0 1/218 (0.5%) 1
    Extravasation 1/438 (0.2%) 1 0/218 (0%) 0
    Face oedema 6/438 (1.4%) 7 2/218 (0.9%) 2
    Facial pain 1/438 (0.2%) 1 0/218 (0%) 0
    Fatigue 145/438 (33.1%) 227 49/218 (22.5%) 63
    Feeling abnormal 1/438 (0.2%) 1 0/218 (0%) 0
    Gait disturbance 1/438 (0.2%) 1 0/218 (0%) 0
    General physical health deterioration 7/438 (1.6%) 9 0/218 (0%) 0
    Influenza like illness 10/438 (2.3%) 17 3/218 (1.4%) 4
    Injection site reaction 4/438 (0.9%) 4 0/218 (0%) 0
    Irritability 1/438 (0.2%) 1 0/218 (0%) 0
    Localised oedema 4/438 (0.9%) 4 0/218 (0%) 0
    Malaise 2/438 (0.5%) 4 0/218 (0%) 0
    Mucosal inflammation 12/438 (2.7%) 19 2/218 (0.9%) 2
    Obstruction 1/438 (0.2%) 1 0/218 (0%) 0
    Oedema 12/438 (2.7%) 16 1/218 (0.5%) 1
    Oedema peripheral 27/438 (6.2%) 34 2/218 (0.9%) 3
    Pain 24/438 (5.5%) 28 13/218 (6%) 13
    Peripheral coldness 0/438 (0%) 0 1/218 (0.5%) 1
    Pyrexia 56/438 (12.8%) 78 25/218 (11.5%) 33
    Swelling 1/438 (0.2%) 1 0/218 (0%) 0
    Visceral oedema 1/438 (0.2%) 1 0/218 (0%) 0
    Hepatobiliary disorders
    Cholelithiasis 1/438 (0.2%) 1 0/218 (0%) 0
    Hepatic pain 0/438 (0%) 0 1/218 (0.5%) 1
    Hepatitis 1/438 (0.2%) 1 0/218 (0%) 0
    Hepatomegaly 1/438 (0.2%) 1 0/218 (0%) 0
    Hyperbilirubinaemia 1/438 (0.2%) 1 1/218 (0.5%) 1
    Immune system disorders
    Contrast media allergy 1/438 (0.2%) 1 0/218 (0%) 0
    Hypersensitivity 6/438 (1.4%) 8 1/218 (0.5%) 1
    Seasonal allergy 1/438 (0.2%) 1 0/218 (0%) 0
    Infections and infestations
    Abscess 2/438 (0.5%) 2 0/218 (0%) 0
    Bronchitis 15/438 (3.4%) 17 2/218 (0.9%) 2
    Candidiasis 2/438 (0.5%) 2 0/218 (0%) 0
    Cellulitis 1/438 (0.2%) 2 1/218 (0.5%) 1
    Cystitis 2/438 (0.5%) 3 0/218 (0%) 0
    Diverticulitis 1/438 (0.2%) 1 0/218 (0%) 0
    Ear infection 0/438 (0%) 0 1/218 (0.5%) 1
    Erysipelas 2/438 (0.5%) 2 0/218 (0%) 0
    Folliculitis 1/438 (0.2%) 1 0/218 (0%) 0
    Fungal infection 1/438 (0.2%) 1 0/218 (0%) 0
    Gastroenteritis 2/438 (0.5%) 2 0/218 (0%) 0
    Gastroenteritis viral 1/438 (0.2%) 1 0/218 (0%) 0
    Hepatic infection 0/438 (0%) 0 1/218 (0.5%) 1
    Herpes simplex 1/438 (0.2%) 1 0/218 (0%) 0
    Herpes virus infection 1/438 (0.2%) 1 0/218 (0%) 0
    Herpes zoster 3/438 (0.7%) 3 1/218 (0.5%) 1
    Infection 3/438 (0.7%) 3 3/218 (1.4%) 3
    Influenza 10/438 (2.3%) 12 0/218 (0%) 0
    Laryngitis 0/438 (0%) 0 2/218 (0.9%) 2
    Lower respiratory tract infection 1/438 (0.2%) 1 0/218 (0%) 0
    Lung infection 3/438 (0.7%) 3 1/218 (0.5%) 1
    Nasopharyngitis 14/438 (3.2%) 17 3/218 (1.4%) 3
    Oral candidiasis 4/438 (0.9%) 4 0/218 (0%) 0
    Oral herpes 0/438 (0%) 0 2/218 (0.9%) 2
    Otitis media 1/438 (0.2%) 1 0/218 (0%) 0
    Paronychia 2/438 (0.5%) 2 0/218 (0%) 0
    Parotitis 1/438 (0.2%) 1 0/218 (0%) 0
    Pharyngitis 1/438 (0.2%) 1 0/218 (0%) 0
    Pneumonia 2/438 (0.5%) 2 2/218 (0.9%) 2
    Pyothorax 0/438 (0%) 0 1/218 (0.5%) 1
    Respiratory tract infection 1/438 (0.2%) 1 0/218 (0%) 0
    Respiratory tract infection viral 1/438 (0.2%) 1 0/218 (0%) 0
    Rhinitis 2/438 (0.5%) 2 0/218 (0%) 0
    Sinusitis 3/438 (0.7%) 3 0/218 (0%) 0
    Soft tissue infection 1/438 (0.2%) 1 0/218 (0%) 0
    Tonsillitis 1/438 (0.2%) 1 0/218 (0%) 0
    Tooth abscess 1/438 (0.2%) 1 0/218 (0%) 0
    Tooth infection 1/438 (0.2%) 1 0/218 (0%) 0
    Upper respiratory tract infection 15/438 (3.4%) 20 3/218 (1.4%) 3
    Urinary tract infection 5/438 (1.1%) 7 4/218 (1.8%) 4
    Injury, poisoning and procedural complications
    Arterial injury 0/438 (0%) 0 1/218 (0.5%) 1
    Contusion 3/438 (0.7%) 3 1/218 (0.5%) 1
    Fall 1/438 (0.2%) 1 0/218 (0%) 0
    Foot fracture 0/438 (0%) 0 1/218 (0.5%) 1
    Fracture 1/438 (0.2%) 1 0/218 (0%) 0
    Incision site pain 0/438 (0%) 0 1/218 (0.5%) 1
    Procedural headache 1/438 (0.2%) 1 0/218 (0%) 0
    Radiation skin injury 1/438 (0.2%) 1 1/218 (0.5%) 1
    Rib fracture 0/438 (0%) 0 1/218 (0.5%) 1
    Thermal burn 1/438 (0.2%) 1 1/218 (0.5%) 1
    Wound 1/438 (0.2%) 1 0/218 (0%) 0
    Investigations
    Alanine aminotransferase 0/438 (0%) 0 1/218 (0.5%) 1
    Alanine aminotransferase decreased 1/438 (0.2%) 1 1/218 (0.5%) 1
    Alanine aminotransferase increased 60/438 (13.7%) 87 9/218 (4.1%) 11
    Aspartate aminotransferase increased 52/438 (11.9%) 63 8/218 (3.7%) 10
    Blood albumin decreased 2/438 (0.5%) 2 0/218 (0%) 0
    Blood alkaline phosphatase 1/438 (0.2%) 1 1/218 (0.5%) 2
    Blood alkaline phosphatase increased 12/438 (2.7%) 16 4/218 (1.8%) 4
    Blood bicarbonate decreased 1/438 (0.2%) 1 0/218 (0%) 0
    Blood bilirubin increased 1/438 (0.2%) 1 0/218 (0%) 0
    Blood calcium decreased 1/438 (0.2%) 1 0/218 (0%) 0
    Blood creatinine decreased 3/438 (0.7%) 10 1/218 (0.5%) 1
    Blood creatinine increased 21/438 (4.8%) 30 4/218 (1.8%) 4
    Blood fibrinogen increased 1/438 (0.2%) 1 0/218 (0%) 0
    Blood glucose increased 1/438 (0.2%) 3 0/218 (0%) 0
    Blood iron decreased 1/438 (0.2%) 1 0/218 (0%) 0
    Blood lactate dehydrogenase increased 9/438 (2.1%) 15 1/218 (0.5%) 1
    Blood potassium decreased 1/438 (0.2%) 1 0/218 (0%) 0
    Blood potassium increased 1/438 (0.2%) 2 0/218 (0%) 0
    Blood sodium decreased 1/438 (0.2%) 1 0/218 (0%) 0
    Blood sodium increased 1/438 (0.2%) 1 0/218 (0%) 0
    Blood uric acid increased 2/438 (0.5%) 2 0/218 (0%) 0
    C-reactive protein increased 1/438 (0.2%) 1 1/218 (0.5%) 1
    Creatinine renal clearance decreased 18/438 (4.1%) 28 2/218 (0.9%) 2
    Forced expiratory volume decreased 0/438 (0%) 0 1/218 (0.5%) 1
    Gamma-glutamyltransferase increased 6/438 (1.4%) 7 5/218 (2.3%) 5
    Glomerular filtration rate 1/438 (0.2%) 3 0/218 (0%) 0
    Glomerular filtration rate decreased 5/438 (1.1%) 10 0/218 (0%) 0
    Granulocyte count decreased 1/438 (0.2%) 1 0/218 (0%) 0
    Granulocyte count increased 0/438 (0%) 0 1/218 (0.5%) 2
    Haemoglobin 1/438 (0.2%) 1 0/218 (0%) 0
    Haemoglobin decreased 19/438 (4.3%) 30 2/218 (0.9%) 2
    Neutrophil count decreased 11/438 (2.5%) 16 1/218 (0.5%) 1
    Neutrophil count increased 3/438 (0.7%) 4 0/218 (0%) 0
    Platelet count 1/438 (0.2%) 1 0/218 (0%) 0
    Platelet count decreased 5/438 (1.1%) 5 2/218 (0.9%) 2
    Platelet count increased 1/438 (0.2%) 1 2/218 (0.9%) 3
    Red blood cell count decreased 2/438 (0.5%) 5 1/218 (0.5%) 1
    Red blood cell microcytes present 0/438 (0%) 0 1/218 (0.5%) 1
    Renal function test abnormal 1/438 (0.2%) 3 0/218 (0%) 0
    Sensory level 1/438 (0.2%) 1 0/218 (0%) 0
    Transaminases increased 1/438 (0.2%) 1 0/218 (0%) 0
    Troponin t 1/438 (0.2%) 1 0/218 (0%) 0
    Weight decreased 17/438 (3.9%) 20 3/218 (1.4%) 3
    Weight increased 5/438 (1.1%) 5 1/218 (0.5%) 1
    White blood cell count decreased 4/438 (0.9%) 5 0/218 (0%) 0
    White blood cell count increased 1/438 (0.2%) 1 2/218 (0.9%) 3
    Metabolism and nutrition disorders
    Acidosis 1/438 (0.2%) 1 0/218 (0%) 0
    Alcohol intolerance 1/438 (0.2%) 1 0/218 (0%) 0
    Alkalosis 1/438 (0.2%) 1 0/218 (0%) 0
    Anorexia 124/438 (28.3%) 238 40/218 (18.3%) 43
    Dehydration 7/438 (1.6%) 8 1/218 (0.5%) 1
    Diabetes mellitus 3/438 (0.7%) 3 0/218 (0%) 0
    Fluid retention 2/438 (0.5%) 3 0/218 (0%) 0
    Glucose tolerance impaired 1/438 (0.2%) 1 0/218 (0%) 0
    Hypercalcaemia 3/438 (0.7%) 3 2/218 (0.9%) 3
    Hypercholesterolaemia 1/438 (0.2%) 2 1/218 (0.5%) 1
    Hypercreatininaemia 1/438 (0.2%) 1 0/218 (0%) 0
    Hyperglycaemia 18/438 (4.1%) 20 6/218 (2.8%) 7
    Hyperkalaemia 4/438 (0.9%) 6 1/218 (0.5%) 1
    Hyperlipidaemia 1/438 (0.2%) 1 0/218 (0%) 0
    Hypernatraemia 2/438 (0.5%) 3 0/218 (0%) 0
    Hypertriglyceridaemia 0/438 (0%) 0 1/218 (0.5%) 1
    Hyperuricaemia 1/438 (0.2%) 1 3/218 (1.4%) 3
    Hypoalbuminaemia 2/438 (0.5%) 3 1/218 (0.5%) 1
    Hypocalcaemia 2/438 (0.5%) 2 0/218 (0%) 0
    Hypokalaemia 4/438 (0.9%) 4 1/218 (0.5%) 2
    Hyponatraemia 7/438 (1.6%) 7 0/218 (0%) 0
    Hypophosphataemia 0/438 (0%) 0 1/218 (0.5%) 2
    Increased appetite 1/438 (0.2%) 1 0/218 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 12/438 (2.7%) 16 7/218 (3.2%) 7
    Arthritis 1/438 (0.2%) 1 0/218 (0%) 0
    Back pain 41/438 (9.4%) 48 8/218 (3.7%) 8
    Bone pain 14/438 (3.2%) 14 10/218 (4.6%) 10
    Flank pain 1/438 (0.2%) 2 1/218 (0.5%) 1
    Muscle spasms 3/438 (0.7%) 3 0/218 (0%) 0
    Muscular weakness 5/438 (1.1%) 6 2/218 (0.9%) 2
    Musculoskeletal chest pain 8/438 (1.8%) 8 5/218 (2.3%) 5
    Musculoskeletal discomfort 1/438 (0.2%) 1 0/218 (0%) 0
    Musculoskeletal pain 12/438 (2.7%) 14 5/218 (2.3%) 6
    Myalgia 15/438 (3.4%) 17 5/218 (2.3%) 7
    Neck pain 3/438 (0.7%) 5 5/218 (2.3%) 6
    Pain in extremity 11/438 (2.5%) 14 9/218 (4.1%) 11
    Pain in jaw 2/438 (0.5%) 7 0/218 (0%) 0
    Scleroderma 1/438 (0.2%) 1 0/218 (0%) 0
    Tendonitis 1/438 (0.2%) 1 0/218 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Angiolipoma 1/438 (0.2%) 1 0/218 (0%) 0
    Cancer pain 11/438 (2.5%) 11 4/218 (1.8%) 4
    Metastatic pain 1/438 (0.2%) 1 0/218 (0%) 0
    Neoplasm 0/438 (0%) 0 1/218 (0.5%) 1
    Oesophageal carcinoma 1/438 (0.2%) 1 0/218 (0%) 0
    Tumour pain 5/438 (1.1%) 5 5/218 (2.3%) 5
    Nervous system disorders
    Ageusia 0/438 (0%) 0 1/218 (0.5%) 1
    Aphasia 1/438 (0.2%) 1 0/218 (0%) 0
    Aphonia 1/438 (0.2%) 1 0/218 (0%) 0
    Ataxia 5/438 (1.1%) 6 0/218 (0%) 0
    Balance disorder 1/438 (0.2%) 1 0/218 (0%) 0
    Brain injury 1/438 (0.2%) 1 0/218 (0%) 0
    Burning sensation 1/438 (0.2%) 1 0/218 (0%) 0
    Cerebral ischaemia 0/438 (0%) 0 2/218 (0.9%) 2
    Cognitive disorder 2/438 (0.5%) 2 1/218 (0.5%) 1
    Coma 1/438 (0.2%) 1 0/218 (0%) 0
    Convulsion 3/438 (0.7%) 3 1/218 (0.5%) 1
    Depressed level of consciousness 1/438 (0.2%) 1 0/218 (0%) 0
    Disturbance in attention 1/438 (0.2%) 1 0/218 (0%) 0
    Dizziness 34/438 (7.8%) 39 7/218 (3.2%) 7
    Dysaesthesia 1/438 (0.2%) 2 1/218 (0.5%) 1
    Dysgeusia 10/438 (2.3%) 14 1/218 (0.5%) 1
    Dysphasia 2/438 (0.5%) 2 0/218 (0%) 0
    Formication 1/438 (0.2%) 1 0/218 (0%) 0
    Headache 51/438 (11.6%) 62 19/218 (8.7%) 26
    Hemicephalalgia 1/438 (0.2%) 1 0/218 (0%) 0
    Hemiparesis 1/438 (0.2%) 1 0/218 (0%) 0
    Hypoaesthesia 5/438 (1.1%) 6 3/218 (1.4%) 3
    Memory impairment 2/438 (0.5%) 2 0/218 (0%) 0
    Neuralgia 4/438 (0.9%) 4 1/218 (0.5%) 1
    Neuropathy peripheral 10/438 (2.3%) 11 2/218 (0.9%) 2
    Neurotoxicity 1/438 (0.2%) 1 0/218 (0%) 0
    Paraesthesia 27/438 (6.2%) 29 11/218 (5%) 12
    Peripheral motor neuropathy 1/438 (0.2%) 1 0/218 (0%) 0
    Peripheral sensory neuropathy 22/438 (5%) 22 6/218 (2.8%) 6
    Poor quality sleep 1/438 (0.2%) 1 0/218 (0%) 0
    Somnolence 0/438 (0%) 0 1/218 (0.5%) 1
    Speech disorder 2/438 (0.5%) 2 0/218 (0%) 0
    Stupor 1/438 (0.2%) 1 0/218 (0%) 0
    Syncope 1/438 (0.2%) 1 1/218 (0.5%) 1
    Syncope vasovagal 2/438 (0.5%) 2 0/218 (0%) 0
    Transient ischaemic attack 1/438 (0.2%) 1 0/218 (0%) 0
    Tremor 3/438 (0.7%) 3 0/218 (0%) 0
    Psychiatric disorders
    Abnormal behaviour 1/438 (0.2%) 1 0/218 (0%) 0
    Agitation 0/438 (0%) 0 1/218 (0.5%) 1
    Anxiety 5/438 (1.1%) 5 1/218 (0.5%) 1
    Confusional state 4/438 (0.9%) 4 0/218 (0%) 0
    Depressed mood 3/438 (0.7%) 3 0/218 (0%) 0
    Depression 9/438 (2.1%) 9 1/218 (0.5%) 1
    Insomnia 28/438 (6.4%) 31 8/218 (3.7%) 8
    Suicidal ideation 1/438 (0.2%) 1 0/218 (0%) 0
    Tic 1/438 (0.2%) 1 0/218 (0%) 0
    Renal and urinary disorders
    Bladder spasm 1/438 (0.2%) 1 0/218 (0%) 0
    Calculus bladder 1/438 (0.2%) 1 0/218 (0%) 0
    Dysuria 3/438 (0.7%) 8 0/218 (0%) 0
    Glycosuria 1/438 (0.2%) 1 0/218 (0%) 0
    Haematuria 1/438 (0.2%) 1 0/218 (0%) 0
    Haemorrhage urinary tract 0/438 (0%) 0 1/218 (0.5%) 1
    Incontinence 1/438 (0.2%) 1 0/218 (0%) 0
    Micturition urgency 0/438 (0%) 0 1/218 (0.5%) 1
    Nocturia 1/438 (0.2%) 1 0/218 (0%) 0
    Pollakiuria 3/438 (0.7%) 4 0/218 (0%) 0
    Renal failure 3/438 (0.7%) 3 0/218 (0%) 0
    Urinary hesitation 1/438 (0.2%) 3 0/218 (0%) 0
    Urinary incontinence 1/438 (0.2%) 1 2/218 (0.9%) 2
    Urinary retention 5/438 (1.1%) 5 0/218 (0%) 0
    Reproductive system and breast disorders
    Balanitis 1/321 (0.3%) 1 0/158 (0%) 0
    Breast swelling 0/438 (0%) 0 1/218 (0.5%) 1
    Pelvic pain 1/438 (0.2%) 1 1/218 (0.5%) 1
    Testicular disorder 1/321 (0.3%) 1 0/158 (0%) 0
    Testicular pain 1/321 (0.3%) 1 0/158 (0%) 0
    Vaginal haemorrhage 2/117 (1.7%) 2 0/60 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 0/438 (0%) 0 1/218 (0.5%) 1
    Bronchial obstruction 1/438 (0.2%) 1 0/218 (0%) 0
    Cough 95/438 (21.7%) 118 47/218 (21.6%) 50
    Dysphonia 2/438 (0.5%) 2 4/218 (1.8%) 4
    Dyspnoea 98/438 (22.4%) 118 43/218 (19.7%) 45
    Dyspnoea exertional 2/438 (0.5%) 2 1/218 (0.5%) 1
    Epistaxis 5/438 (1.1%) 8 1/218 (0.5%) 1
    Haemoptysis 24/438 (5.5%) 26 10/218 (4.6%) 11
    Hiccups 9/438 (2.1%) 17 3/218 (1.4%) 3
    Hypoxia 3/438 (0.7%) 3 0/218 (0%) 0
    Pharyngolaryngeal pain 10/438 (2.3%) 11 5/218 (2.3%) 5
    Pleural effusion 2/438 (0.5%) 2 0/218 (0%) 0
    Pleurisy 1/438 (0.2%) 1 0/218 (0%) 0
    Pleuritic pain 1/438 (0.2%) 1 0/218 (0%) 0
    Pneumonitis 2/438 (0.5%) 2 0/218 (0%) 0
    Postnasal drip 3/438 (0.7%) 5 0/218 (0%) 0
    Productive cough 11/438 (2.5%) 15 3/218 (1.4%) 3
    Pulmonary embolism 0/438 (0%) 0 1/218 (0.5%) 1
    Pulmonary haemorrhage 0/438 (0%) 0 3/218 (1.4%) 3
    Rales 1/438 (0.2%) 1 0/218 (0%) 0
    Rhinitis allergic 4/438 (0.9%) 7 1/218 (0.5%) 1
    Rhinorrhoea 6/438 (1.4%) 6 0/218 (0%) 0
    Rhonchi 1/438 (0.2%) 1 0/218 (0%) 0
    Wheezing 4/438 (0.9%) 4 1/218 (0.5%) 1
    Skin and subcutaneous tissue disorders
    Acne 1/438 (0.2%) 2 2/218 (0.9%) 2
    Alopecia 21/438 (4.8%) 23 1/218 (0.5%) 1
    Dermal cyst 1/438 (0.2%) 1 0/218 (0%) 0
    Dermatitis acneiform 2/438 (0.5%) 6 4/218 (1.8%) 4
    Dermatitis exfoliative 1/438 (0.2%) 1 0/218 (0%) 0
    Dermatosis 1/438 (0.2%) 2 0/218 (0%) 0
    Dry skin 5/438 (1.1%) 6 1/218 (0.5%) 1
    Erythema 2/438 (0.5%) 2 0/218 (0%) 0
    Hyperhidrosis 12/438 (2.7%) 15 0/218 (0%) 0
    Madarosis 1/438 (0.2%) 1 0/218 (0%) 0
    Nail disorder 0/438 (0%) 0 1/218 (0.5%) 1
    Night sweats 2/438 (0.5%) 2 1/218 (0.5%) 1
    Pain of skin 0/438 (0%) 0 2/218 (0.9%) 2
    Periorbital oedema 1/438 (0.2%) 1 0/218 (0%) 0
    Petechiae 2/438 (0.5%) 5 0/218 (0%) 0
    Photosensitivity reaction 1/438 (0.2%) 1 0/218 (0%) 0
    Pigmentation disorder 4/438 (0.9%) 7 0/218 (0%) 0
    Pruritus 18/438 (4.1%) 22 7/218 (3.2%) 8
    Pruritus generalised 1/438 (0.2%) 1 0/218 (0%) 0
    Psoriasis 1/438 (0.2%) 1 0/218 (0%) 0
    Rash 62/438 (14.2%) 81 14/218 (6.4%) 16
    Rash pruritic 3/438 (0.7%) 3 0/218 (0%) 0
    Skin discolouration 1/438 (0.2%) 1 0/218 (0%) 0
    Skin exfoliation 1/438 (0.2%) 1 0/218 (0%) 0
    Skin hyperpigmentation 9/438 (2.1%) 9 1/218 (0.5%) 1
    Skin hypopigmentation 1/438 (0.2%) 1 0/218 (0%) 0
    Skin toxicity 1/438 (0.2%) 1 0/218 (0%) 0
    Swelling face 2/438 (0.5%) 2 0/218 (0%) 0
    Urticaria 1/438 (0.2%) 4 0/218 (0%) 0
    Surgical and medical procedures
    Medical device implantation 1/438 (0.2%) 1 0/218 (0%) 0
    Pneumatic compression therapy 1/438 (0.2%) 1 0/218 (0%) 0
    Tumour excision 1/438 (0.2%) 1 0/218 (0%) 0
    Vascular disorders
    Deep vein thrombosis 1/438 (0.2%) 1 0/218 (0%) 0
    Flushing 8/438 (1.8%) 10 5/218 (2.3%) 7
    Haemorrhage 1/438 (0.2%) 1 0/218 (0%) 0
    Hot flush 2/438 (0.5%) 2 1/218 (0.5%) 1
    Hypertension 11/438 (2.5%) 11 4/218 (1.8%) 4
    Hypotension 6/438 (1.4%) 6 3/218 (1.4%) 3
    Orthostatic hypotension 1/438 (0.2%) 1 1/218 (0.5%) 1
    Peripheral ischaemia 1/438 (0.2%) 1 0/218 (0%) 0
    Phlebitis 2/438 (0.5%) 2 0/218 (0%) 0
    Shock 1/438 (0.2%) 1 0/218 (0%) 0
    Superior vena caval occlusion 3/438 (0.7%) 3 1/218 (0.5%) 1
    Thrombosis 3/438 (0.7%) 3 2/218 (0.9%) 2

    Limitations/Caveats

    Four participants (pts) assigned to placebo received pemetrexed; pts analyzed for efficacy as randomized. Three treated pts did not sign ICF, 1 treated pt signed ICF but did not complete entire randomization process; pts excluded from all analyses.

    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.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT00102804
    Other Study ID Numbers:
    • 5122
    • H3E-MC-JMEN
    First Posted:
    Feb 2, 2005
    Last Update Posted:
    Dec 29, 2014
    Last Verified:
    Dec 1, 2014