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

• ClinicalTrials.gov Identifier: NCT00102804
• Recruitment Status: Completed
• First Posted: February 2, 2005
• Results First Posted: December 29, 2014
• Last Update Posted: December 29, 2014
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: February 1, 2005
• First Posted Date: February 2, 2005
• Results First Submitted Date: December 17, 2014
• Results First Posted Date: December 29, 2014
• Last Update Posted Date: December 29, 2014
• Study Start Date: March 2005
• Actual Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 17, 2014)

Progression-Free Survival (PFS) Time [ Time Frame: 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.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: December 17, 2014)

• Overall Survival (OS) Time [ Time Frame: 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.
• Time to Objective Progressive Disease (TPD) [ Time Frame: 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.
• Time to Worsening of Symptoms (TWS) [ Time Frame: 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.
• 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) ]
  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) ]
  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) ]
  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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pemetrexed and Best Supportive Care Versus Placebo and Best Supportive Care in Non-Small Cell Lung Cancer (NSCLC)
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

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

  • LY231514
  • Alimta
• 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.

Study Arms

• Experimental: Pemetrexed and Best Supportive Care
  Interventions:

  • Drug: Pemetrexed
  • Other: Best Supportive Care
• Placebo Comparator: Placebo and Best Supportive Care
  Interventions:

  • Drug: Placebo
  • Other: Best Supportive Care

Publications *

• Belani CP, Brodowicz T, Ciuleanu TE, Krzakowski M, Yang SH, Franke F, Cucevic B, Madhavan J, Santoro A, Ramlau R, Liepa AM, Visseren-Grul C, Peterson P, John WJ, Zielinski CC. Quality of life in patients with advanced non-small-cell lung cancer given maintenance treatment with pemetrexed versus placebo (H3E-MC-JMEN): results from a randomised, double-blind, phase 3 study. Lancet Oncol. 2012 Mar;13(3):292-9. doi: 10.1016/S1470-2045(11)70339-4. Epub 2012 Feb 14.
• Gridelli C, Brodowicz T, Langer CJ, Peterson P, Islam M, Guba SC, Moore P, Visseren-Grul CM, Scagliotti G. Pemetrexed therapy in elderly patients with good performance status: analysis of two phase III trials of patients with nonsquamous non-small-cell lung cancer. Clin Lung Cancer. 2012 Sep;13(5):340-6. doi: 10.1016/j.cllc.2011.12.002. Epub 2012 Jan 23.
• Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, Wu YL, Bover I, Begbie S, Tzekova V, Cucevic B, Pereira JR, Yang SH, Madhavan J, Sugarman KP, Peterson P, John WJ, Krejcy K, Belani CP. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet. 2009 Oct 24;374(9699):1432-40. doi: 10.1016/S0140-6736(09)61497-5. Epub 2009 Sep 18.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 17, 2014): 663
• Original Enrollment: Not Provided
• Actual Study Completion Date: December 2013
• Actual Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Brazil, Bulgaria, China, Croatia, Czech Republic, Germany, Greece, Hungary, India, Italy, Korea, Republic of, Netherlands, Poland, Romania, Spain, Taiwan, Turkey, United States

Administrative Information

• NCT Number: NCT00102804
• Other Study ID Numbers: 5122; H3E-MC-JMEN ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Not Provided
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: Eli Lilly and Company
• Verification Date: December 2014