A Study of Tarceva (Erlotinib) or Placebo in Combination With Platinum-Based Therapy as First Line Treatment in Patients With Advanced or Recurrent Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT00883779
• Recruitment Status: Completed
• First Posted: April 20, 2009
• Results First Posted: December 14, 2015
• Last Update Posted: December 14, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: April 15, 2009
• First Posted Date: April 20, 2009
• Results First Submitted Date: November 10, 2015
• Results First Posted Date: December 14, 2015
• Last Update Posted Date: December 14, 2015
• Study Start Date: April 2009
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 10, 2015)

Median Progression Free Survival (PFS) Time [ Time Frame: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years]) ]

Tumor response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (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. PFS is the time (in months) between the date of randomization and the date of first documented disease progression or death from any cause, whichever comes first. Participants who had neither progressed nor died at the time of data cut-off or who were lost to follow-up were censored at the date of the last tumor assessment where non-progression was documented or last date of follow up for progression of disease, whichever was last. Participants without post baseline tumor assessments who were known to be alive were censored at the time of randomization. Analysis was performed using Kaplan-Meier method.

• Original Primary Outcome Measures (submitted: April 17, 2009): Progression-free survival [ Time Frame: Event driven--tumor assessments every 8 weeks ]

Current Secondary Outcome Measures (submitted: November 10, 2015)

• Percentage of Participants Alive and Free From Disease Progression [ Time Frame: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years]) ]
  Tumor response was evaluated according to RECIST (version 1.0). PD was defined as 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.
• Median PFS Time Based on Different Subgroups [ Time Frame: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years]) ]
  Tumor response was evaluated according to RECIST (version 1.0). PD was defined in outcome measure 1. PFS is the time (in months) between the date of randomization and the date of first documented disease progression or death from any cause, whichever comes first. Participants who had neither progressed nor died at the time of data cut-off or who were lost to follow-up were censored at the date of the last tumor assessment where non-progression was documented or last date of follow up for progression of disease, whichever was last. Participants without post baseline tumor assessments who were known to be alive were censored at the time of randomization. PFS among different subgroups of type of carcinoma, smoking habit, epidermal growth factor receptor (EGFR) mutation type, KRAS mutation type, EGFR immunohistochemistry (IHC) test result type, and EGFR fluorescent in situ hybridization (FISH) result type.
• Median Overall Survival (OS) Time-Overall and Among Different Subgroups [ Time Frame: Randomization until death (assessed at baseline and every 8 weeks thereafter until death or end of study [up to approximately 5.5 years]) ]
  OS was defined as the time between the date of randomization and the date of death from any cause. Participants for whom no death was captured on the clinical database were censored at the most recent date they were known to be alive. Participants with no post baseline information were censored at the time of randomization. OS among different subgroups of type of carcinoma, smoking habit, EGFR mutation type, KRAS mutation type, EGFR IHC test result type, and EGFR FISH result type. Analysis was performed using Kaplan-Meier method.
• Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups [ Time Frame: Randomization until death (assessed at baseline and every 8 weeks thereafter until death or end of study [up to approximately 5.5 years]) ]
• Non-Progression Rate: Percentage of Participants With a Confirmed Best Overall Response of Either Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) for At Least 16 Weeks [ Time Frame: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years]) ]
  Tumor response was evaluated according to RECIST (version 1.0). CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level; PR is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the screening sum LD; SD for target lesions is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started and SD for non-target lesions defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. Responses were confirmed with repeated assessment 4 weeks after initial response was observed.
• Objective Response Rate: Percentage of Participants With a Confirmed Best Overall Response of CR or PR [ Time Frame: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years]) ]
  Tumor response was evaluated according to RECIST (version 1.0). CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level; PR is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the screening sum LD. Responses were confirmed with repeated assessment 4 weeks after initial response was observed.
• Duration of Response [ Time Frame: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years]) ]
  Duration of response is defined as the time between the date of first documented response (CR or PR, as determined by the RECIST criteria) and the date of first documented PD or death. Participants who did not progress or die after they had a confirmed response (CR or PR) were censored at the date of their last tumor assessment where non-progression was documented or last date of follow-up for progression of disease, whichever was last. CR and PR are defined in Outcome Measure 7.
• Time to Progression [ Time Frame: Randomization until PD (assessed at baseline and every 8 weeks thereafter until PD or end of study [up to approximately 1.5 years]) ]
  Time to progression is defined as the time between the date of randomization and the date of the first documented disease progression. Participants who have not progressed at the time of study completion (or data cut off) or who were lost to follow up were censored at the date of the last tumor assessment where non-progression was documented or last date of follow-up for progression of disease, whichever was latest. PD was defined as 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. Participants with no post baseline tumor assessments were censored at the time of randomization. Analysis was performed using Kaplan-Meier method.
• Percentage of Participants With Symptomatic Progression Assessed Using the Lung Cancer Subscale (LCS) [ Time Frame: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years) ]
  LCS scores were obtained from a 7-item questionnaire from the Functional Assessment of Cancer Therapy - Lung (FACT-L) (version 4.0). Participants responded to questions such as shortness of breath, cough, tightness in chest, breathing difficulty, appetite loss, weight loss and unclear thinking; on a 5-point scale from 0-4, where 0 equaled (=) "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, scores range on a scale of 0 (most symptomatic) to 28 (asymptomatic); higher score indicates fewer symptoms. A clinically meaningful decline used to determine symptomatic progression in this study was at least a three point decline in LCS score from baseline. Participants without symptomatic progression at the time of analysis were censored at the time of the last FACT-L assessment.
• Time to Symptomatic Progression [ Time Frame: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years) ]
  Time to symptomatic progression was the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. LCS scores were obtained from a 7-item questionnaire from the FACT-L (version 4.0). Participants responded to questions such as shortness of breath, cough, tightness in chest, breathing difficulty, appetite loss, weight loss and unclear thinking; on a 5-point scale from 0-4, where 0 = "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, scores range on a scale of 0 (most symptomatic) to 28 (asymptomatic); higher score indicates fewer symptoms. A clinically meaningful decline used to determine symptomatic progression in this study was at least a three point decline in LCS score from baseline. Participants without symptomatic progression at the time of analysis were censored at the time of the last FACT-L assessment. Analysis was performed using Kaplan-Meier method.
• Percentage of Participants With Deterioration in Trial Outcome Index (TOI) Using FACT-L Version 4.0 [ Time Frame: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years) ]
  TOI was defined as the sum of the scores of the Physical Well-Being (PWB), Functional Well-Being (FWB), and LCS. PWB, FWB, and LCS scores were obtained from 7-item questionnaires from the FACT-L (Version 4.0). Participants responded to questions on a 5-point scale from 0-4, where 0 = "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, scores range on a scale of 0 to 84; higher score indicates better physical aspects of quality of life (QoL). A clinically meaningful decline used to determine deterioration in TOI was greater than or equal to (≥) 6-point decline from baseline. Participants without deterioration in TOI at the time of analysis were censored at the time of the last FACT-L assessment.
• Time to Deterioration in TOI Using FACT-L Version 4.0 [ Time Frame: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years) ]
  Time to deterioration in TOI is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in TOI or death on study. TOI is defined as the sum of the scores of the PWB, FWB, and LCS. PWB, FWB, and LCS scores were obtained from 7-item questionnaires from the FACT-L (Version 4.0). Participants responded to questions on a 5-point scale from 0-4, where 0 = "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, scores range on a scale of 0 to 84; higher score indicates better physical aspects of QoL. A clinically meaningful decline used to determine deterioration in TOI was ≥6-point decline from baseline. Participants without deterioration in TOI at the time of analysis were censored at the time of the last FACT-L assessment. Analysis was performed using Kaplan-Meier method.
• Percentage of Participants With Deterioration in Quality of Life (QOL) Using FACT-L Version 4.0 [ Time Frame: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years) ]
  Total FACT-L score was defined as the sum of the TOI, Social Well Being (SWB) and EWB of the FACT-L questionnaires. TOI (PWB + FWB + LCS), SWB and EWB scores were obtained from 7-item (6-item in the case of EWB) questionnaires from the FACT-L (Version 4.0). Participants responded to questions on a 5-point scale from 0-4, where 0 = "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, scores range on a scale of 0 to 136; higher score indicates better QoL. A clinically meaningful decline used to determine deterioration in QoL was ≥6-point decline from baseline. Participants without deterioration in QoL at the time of analysis were censored at the time of the last FACT-L assessment.
• Time to Deterioration in QOL Using FACT-L Version 4.0 [ Time Frame: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years) ]
  Time to deterioration in QoL is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in Total FACT-L or death on study. Total FACT-L score was defined as the sum of the TOI, SWB and EWB of the FACT-L questionnaires. TOI (PWB + FWB + LCS), SWB and EWB scores were obtained from 7-item (6-item in the case of EWB) questionnaires from the FACT-L (Version 4.0). Participants responded to questions on a 5-point scale from 0-4, where 0 = "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, scores range on a scale of 0 to 136; higher score indicates better QoL. A clinically meaningful decline used to determine deterioration in QoL was ≥6-point decline from baseline. Participants without deterioration in QoL at the time of analysis were censored at the time of the last FACT-L assessment. Analysis was performed using Kaplan-Meier method.
• Median Follow-up Time During the Study [ Time Frame: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 5.5 years]) ]
  Median follow-up was calculated using 'Reverse Kaplan-Meier' analysis for Overall survival.

Original Secondary Outcome Measures (submitted: April 17, 2009)

• Objective response rate; duration of response; time to progression; overall survival [ Time Frame: Event driven--tumor assessment every 8 weeks ]
• Non-progression rate [ Time Frame: 16 weeks ]
• AEs, SAEs, laboratory data [ Time Frame: At each clinic visit throughout study ]

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

Descriptive Information

• Brief Title: A Study of Tarceva (Erlotinib) or Placebo in Combination With Platinum-Based Therapy as First Line Treatment in Patients With Advanced or Recurrent Non-Small Cell Lung Cancer
• Official Title: A Randomized, Placebo-controlled, Double-blind Phase III Study of the Effect of First-line Treatment With Intercalated Tarceva Versus Placebo in Combination With Gemcitabine/Platinum on Progression-free Survival in Patients With Stage IIIB/IV Non-small Cell Lung Cancer
• Brief Summary: This 2 arm study will compare the efficacy and safety of sequential treatment with Tarceva or placebo, plus platinum-based therapy, as first line treatment in patients with advanced or recurrent non-small cell lung cancer. Patients will be randomized to receive gemcitabine (1250mg/m2 iv) on days 1 and 8, and cisplatin (75mg/m2) or carboplatin (5xAUC)on day 1, followed by Tarceva 150mg/day or placebo from day 15 to day 28 of each 4 week cycle for a total of 6 cycles,then followed by Tarceva or placebo monotherapy.The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-Squamous Non-Small Cell Lung Cancer

Intervention

• Drug: Placebo
  po on days 15-28 of each 4 week cycle until disease progression
• Drug: Platinum chemotherapy (cisplatin or carboplatin)
  cisplatin --75mg/m2 oon day 1 of each 4 week cycle for 6 cycles or carboplatin--5xAUC on day 1 of each 4 week cycle for 6 cycles
• Drug: erlotinib [Tarceva]
  150mg po on days 15-28 of each 4 week cycle until disease progression
• Drug: gemcitabine
  1250mg/m2 iv on days 1 and 8 of each 4 week cycle for 6 cycles

Study Arms

• Experimental: 1
  Interventions:

  • Drug: Platinum chemotherapy (cisplatin or carboplatin)
  • Drug: erlotinib [Tarceva]
  • Drug: gemcitabine
• Placebo Comparator: 2
  Interventions:

  • Drug: Placebo
  • Drug: Platinum chemotherapy (cisplatin or carboplatin)
  • Drug: gemcitabine

• Publications *: Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013 Jul;14(8):777-86. doi: 10.1016/S1470-2045(13)70254-7. Epub 2013 Jun 17.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 8, 2014): 451
• Original Estimated Enrollment (submitted: April 17, 2009): 450
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• adult patients, >=18 years of age;
• advanced (stage IIIB/IV)non-small cell lung cancer;
• measurable disease;
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.

Exclusion Criteria:

• prior exposure to agents directed at the HER axis;
• prior chemotherapy or systemic anti-tumor therapy after advanced disease;
• unstable systemic disease;
• any other malignancy within last 5 years, except cured basal cell cancer of skin or cured cancer in situ of cervix;
• brain metastasis or spinal cord compression.

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: China, Hong Kong, Indonesia, Korea, Republic of, Philippines, Taiwan, Thailand

Administrative Information

• NCT Number: NCT00883779
• Other Study ID Numbers: MO22201
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Clinical Trials, Study Director, Hoffmann-La Roche
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: November 2015