BIBW 2992 and BSC Versus Placebo and BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-LUNG 1)

• ClinicalTrials.gov Identifier: NCT00656136
• Recruitment Status: Completed
• First Posted: April 10, 2008
• Results First Posted: November 27, 2013
• Last Update Posted: July 26, 2016
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: April 4, 2008
• First Posted Date: April 10, 2008
• Results First Submitted Date: August 8, 2013
• Results First Posted Date: November 27, 2013
• Last Update Posted Date: July 26, 2016
• Study Start Date: April 2008
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 15, 2014)

Overall Survival [ Time Frame: From randomization until death or the last patient out date, an average of 12 months ]

Overall survival was the duration from the date of randomization to the date of death. Patients who were alive were censored at the last contact date prior to the database lock. For the primary analysis 11 patients were lost to follow-up and were censored at the last contact date when they were known to be still alive. Primary analysis data cut-off date was 08 July 2010. For the final analysis 13 patients were lost to follow-up and were censored at the last contact date when they were known to be still alive. Final analysis data cut-off date was 04 October 2013.

• Original Primary Outcome Measures (submitted: April 9, 2008): Overall survival time (OS) [ Time Frame: 9 months ]

Current Secondary Outcome Measures (submitted: September 25, 2014)

• Progression-free Survival (PFS) [ Time Frame: From randomization to disease progression, death or the data cutoff on 07 July 2010, an average of 3.3 months ]
  PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST 1.0).
• Objective Response Rate (OR) [ Time Frame: From randomization to disease progression, death or the data cutoff on 07 July 2010, an average of 3.3 months ]
  OR is defined as complete response (CR) and partial response (PR). Assessed by central independent review according to RECIST 1.0.

Original Secondary Outcome Measures (submitted: April 9, 2008)

• PFS, ORR, Duration of clinical benefit [ Time Frame: 7 months ]
• Time to ORR [ Time Frame: 7 months ]
• Duration of ORR [ Time Frame: 7 months ]
• Safety and PK of BIBW 2992 [ Time Frame: 7 months ]
• HRQOL [ Time Frame: 7 months ]

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

Descriptive Information

• Brief Title: BIBW 2992 and BSC Versus Placebo and BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-LUNG 1)
• Official Title: Phase IIb/III Randomized, Double-blind Trial of BIBW 2992 Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-Lung 1)

Brief Summary

This randomized, double-blind, multi-center Phase IIb/III trial will be performed in patients with NSCLC who have received previous treatment with at least one but not more than two lines of cytotoxic chemotherapy (one line must have been a platinum-containing regimen) and either gefitinib or erlotinib for a period of at least 12 weeks and then progressed.

The primary objective of this randomized trial is to determine the efficacy of BIBW 2992 as a single agent (Arm A) as compared to a matching placebo (Arm B) in this patient population. Patients on both treatment arms will receive best supportive care in addition to study treatment.

Patients enrolled into the trial will be treated and followed until death or lost to follow-up.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung

Intervention

• Drug: placebo
  Patients receive placebo once daily
• Drug: BIBW 2992
  Patients receive afatinib tablets once daily, and can reduce dose for adverse event management. Afatinib is given once daily, continuously until disease progression or unacceptable toxicity.

Study Arms

• Placebo Comparator: Placebo
  Patients receive placebo once daily
  Intervention: Drug: placebo
• Experimental: BIBW 2992
  Patients receive BIBW 2992 tablets once daily
  Intervention: Drug: BIBW 2992

• Publications *: Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. doi: 10.1016/S1470-2045(12)70087-6. Epub 2012 Mar 26. Erratum In: Lancet Oncol. 2012 May;13(5):e186.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 17, 2010): 585
• Original Enrollment (submitted: April 9, 2008): 400
• Actual Study Completion Date: October 2013
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

1. Patients with pathologic confirmation of NSCLC Stage III-B (with pleural effusion) or Stage IV adenocarcinoma who have failed at least one but not more than two lines of cytotoxic chemotherapy (including adjuvant chemotherapy). One of the chemotherapy regimens must have been platinum-based.
2. Progressive disease following at least 12 weeks of treatment with erlotinib (Tarceva®) or gefitinib (Iressa®)
3. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance Score 0, 1 or 2
4. Patients with at least one tumor lesion that can accurately be measured by magnetic resonance imaging (MRI), or computed tomography (CT) in at least one dimension with longest diameter to be recorded as >20 mm using conventional techniques or >10 mm with spiral CT scan
5. Male and female patients age >18 years
6. Life expectancy of at least three (3) months
7. Written informed consent that is consistent with ICH-GCP guidelines

Exclusion criteria:

1. Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within 14 days of treatment Day 1
2. Chemo-, hormone- (other than megestrol acetate or steroids required for maintenance non-cancer therapy) or immunotherapy within the past 4 weeks
3. Active brain metastases
4. Significant or recent acute gastrointestinal disorders with diarrhea
5. Patients who have any other life-threatening illness or organ system dysfunction,
6. Other malignancies diagnosed within the past five (5) years
7. Radiotherapy within the past 2 weeks prior to treatment
8. History of clinically significant or uncontrolled cardiac disease
9. Adequate ANC and platelet count
10. Adequate liver and kidney function
11. Patients with any serious active infection including known HIV, active hepatitis B or active hepatitis C

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: Belgium, Canada, China, France, Germany, Hong Kong, Italy, Korea, Republic of, Netherlands, Singapore, Spain, Taiwan, Thailand, United Kingdom, United States

Administrative Information

• NCT Number: NCT00656136
• Other Study ID Numbers: 1200.23; 2007-005983-28 ( EudraCT Number: EudraCT )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Boehringer Ingelheim
• Original Responsible Party: Not Provided
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

• PRS Account: Boehringer Ingelheim
• Verification Date: June 2016