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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00102804
First received: February 1, 2005
Last updated: December 17, 2014
Last verified: December 2014
  Purpose

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 Intervention Phase
Non-Small Cell Lung Cancer
Drug: Pemetrexed
Drug: Placebo
Other: Best Supportive Care
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) Time [ Time Frame: Randomization to measured PD or death from any cause (up to 41 months) ] [ Designated as safety issue: No ]
    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:
  • Overall Survival (OS) Time [ Time Frame: Randomization to date of death from any cause (up to 41 months) ] [ Designated as safety issue: No ]
    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 to Objective Progressive Disease (TPD) [ Time Frame: Randomization to measured PD (up to 41 months) ] [ Designated as safety issue: No ]
    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 to Worsening of Symptoms (TWS) [ Time Frame: Randomization to worsening of each LCSS item (up to 39 months) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Tumor Response Rate) [ Time Frame: Baseline to measured PD (up to 41 months) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline to study completion (up to 41 Months) ] [ Designated as safety issue: No ]
    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.

  • Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS [ Time Frame: Baseline through 30 days post discontinuation of study treatment (up to 39 Months) ] [ Designated as safety issue: No ]
    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.


Enrollment: 663
Study Start Date: March 2005
Study Completion Date: December 2013
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00102804

  Show 73 Study Locations
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
  More Information

Additional Information:
No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00102804     History of Changes
Other Study ID Numbers: 5122, H3E-MC-JMEN
Study First Received: February 1, 2005
Results First Received: December 17, 2014
Last Updated: December 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Pemetrexed
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on March 26, 2015