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LUX-Lung 8: A Phase III Trial of Afatinib (BIBW 2992) Versus Erlotinib for the Treatment of Squamous Cell Lung Cancer After at Least One Prior Platinum Based Chemotherapy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01523587
First received: January 30, 2012
Last updated: November 20, 2014
Last verified: November 2014
  Purpose

This randomised, open-label phase III trial will be performed in patients with advanced squamous cell carcinoma of the lung requiring second-line treatment after receiving first-line platinum-based chemotherapy. The primary objective of this trial is to compare the efficacy of BIBW 2992 to erlotinib as second-line treatment in this group of patients.


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: afatinib
Drug: erlotinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: LUX-Lung 8: A Randomized, Open-label Phase III Trial of Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung as Second-line Therapy Following First-line Platinum-based Chemotherapy

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Progression-free Survival, Based on Central Independent Review as Determined by RECIST 1.1 [ Time Frame: First treatment administration up until cut off date of 7th October 2013 (up to 78 weeks). ] [ Designated as safety issue: No ]
    The primary endpoint of this study was Progression Free Survival (PFS), as determined by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. PFS was defined as the time from randomisation to disease progression (or death if the patient died before progression).


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From randomisation until 632 deaths ] [ Designated as safety issue: No ]

    The primary analysis of Overall Survival (OS) will be conducted after 632 deaths have occured. This is predicted to be March 2015.

    Overall Survival is defined as the time from randomisation to death.


  • Objective Response According to RECIST 1.1 [ Time Frame: First treatment administration until cut off date of 7th October 2013 (up to 78 weeks). ] [ Designated as safety issue: No ]
    Objective response as defined by RECIST 1.1 as either complete response (CR) or partial response (PR).

  • Disease Control According to RECIST 1.1 [ Time Frame: First treatment administration until cut off date of 7th October 2013 (up to 78 weeks). ] [ Designated as safety issue: No ]
    Disease control (defined as CR, PR or Stable Disease (SD)) according to RECIST 1.1.

  • Tumour Shrinkage [ Time Frame: First treatment administration until cut off date of 7th October 2013 (up to 78 weeks). ] [ Designated as safety issue: No ]

    Maximum percentage decrease from baseline in the sum of target lesion diameters following independent review.

    The change in the size (i.e. the sum of diameters (SOD)) of target lesions from baseline was derived. Tumour shrinkage for each patient was measured (based on Independent Radiologic Review (IRR)) as the minimum SOD of target lesions after randomisation.

    A negative percentage indicates decrease from baseline; positive numbers indicate an increase of tumour size. The mean maximum decrease from baseline of +5 and +9.4 reflect an average increase in tumour size.


  • Status Change in Cough, Dyspnoea and Pain Related Items Over Time in Health Related Quality of Life Questionnaire [ Time Frame: First treatment administration up to 28 days after the last intake of study medication. ] [ Designated as safety issue: No ]

    Health-related quality of life (HRQoL) was measured with the following multi-dimensional questionnaires: the EORTC QLQ-C30 questionnaire and its lung cancer specific supplementary module EORTC QLQ-LC13 and the EQ-5D health status self-assessment questionnaire. The questionnaires were assessed at the first visit of each treatment course, at EOT and follow up prior to clinical assessment. The results displayed show improvement in the relevant criteria.

    For each of the summary scales and items measuring cough, dyspnoea and pain, the two treatment arms were compared in terms of: The proportion of patients that were improved: Change in cough; dyspnoea and pain scores over time.


  • Summary of Time to Deterioration in Coughing, Dyspnoea and Pain. [ Time Frame: First treatment administration up to 28 days after the last intake of study medication. ] [ Designated as safety issue: No ]
    Health-related quality of life (HRQoL) was measured with the following multi-dimensional questionnaires: the EORTC QLQ-C30. The questionnaires were assessed at the first visit of each treatment course. For each of the summary scales and items measuring cough, dyspnoea and pain, the two treatment arms were compared in terms of: Time to deterioration.

  • Change in Score Over Time in Coughing,Dyspnoea and Pain [ Time Frame: First treatment administration up to 28 days after last intake of study medication ] [ Designated as safety issue: No ]

    Health related quality of life (HRQoL) was measured with the following multi dimensional questionnaires: the EORTC QLQ-C30. The questionnaires were assessed at the first visit of each treatment course. For each of the summary scales and items measuring cough, dyspnoea and pain, the two treatment arms were compared in terms of change in score over time, adjusted for baseline score and race.

    Questionnaires have items relating to Cough, Dyspnoea and Pain. Overall Scores are transformed to a standardised scale of 0 to 100 with the larger value indicating a worse outcome. A change of (+/-) 10 points is considered to be relevant.

    The change in cough, dyspnea and pain will be assessed using a mixed effects growth curve model with the average profile over time for each endpoint described by a piecewise linear model (presented as post baseline in data table).



Enrollment: 795
Study Start Date: March 2012
Estimated Study Completion Date: November 2015
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Afatinib
Patients receive afatinib tablets once daily
Drug: afatinib
Afatinib taken once daily, continuously until disease progression or unacceptable toxicity.
Active Comparator: Erlotinib
Patients receive erlotinib tablets once daily
Drug: erlotinib
erlotinib taken once daily

  Eligibility

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

Inclusion criteria:

  1. Diagnosis of advanced stage NSCLC squamous histology.
  2. Platinum-based doublet chemotherapy as 1st line treatment of Stage IIIB/IV NSCLC.
  3. Eligible to receive 2nd line therapy in the opinion of the investigator.
  4. Measurable disease according to RECIST 1.1.
  5. Adequate Performance Status.
  6. Availability of tumour tissue material for correlative studies. Archived tumour tissue is acceptable.
  7. Adequate organ function.
  8. Age = 18 years and above.
  9. Written informed consent that is consistent with ICH-GCP guidelines.

Exclusion criteria:

  1. Prior treatment with EGFR directed small molecules or antibodies.
  2. Radiotherapy within 4 weeks prior to randomization.
  3. Active brain metastases .
  4. Any other current malignancy or malignancy diagnosed within the past three (3) years (other than basal-cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer).
  5. Known pre-existing interstitial lung disease.
  6. Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom
  7. Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
  8. Women of child-bearing potential and men who are able to father a child, unwilling to be abstinent or use adequate contraception prior to study entry, for the duration of study participation and for at least 2 months after treatment has ended.
  9. Female patients of childbearing potential (see Section 4.2.3.3) who:

    1. are nursing or
    2. are pregnant or
    3. are not using an acceptable method of birth control, or do not plan to continue using this method throughout the study and/or do not agree to submit to pregnancy testing required by this protocol.
  10. Active hepatitis B infection (defined as presence of Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier.
  11. Known or suspected active drug or alcohol abuse in the opinion of the investigator.
  12. Any contraindications for therapy with afatinib or erlotinib.
  13. Known hypersensitivity to erlotinib, afatinib or the excipients of any of the trial drugs.
  14. Major surgery within 4 weeks of starting study treatment.
  15. Prior participation in an afatinib clinical study, even if not assigned to afatinib.
  16. Use of any investigational drug within 4 weeks of randomisation (unless a longer time period is required by local regulations or by the guidelines for the investigational product).
  17. Patients without Progression of their lung cancer.
  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: NCT01523587

  Show 191 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01523587     History of Changes
Other Study ID Numbers: 1200.125, 2011-002380-24
Study First Received: January 30, 2012
Results First Received: October 6, 2014
Last Updated: November 20, 2014
Health Authority: Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica
Austria: Medicines and Medical Devices Agency
Canada: Health Canada
Chile: Instituto de Salud Pública de Chile
China: Food and Drug Administration
Denmark: The Danish Health and Medicines Authority
France: Agence Nationale sécurité médicament et des produits santé
Germany: Paul-Ehrlich-Institute
Greece: Ethics Committee
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Ireland: Irish Medicines Board
Italy: Ethics Committee
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: Central Committee Research Involving Human Subjects
Portugal: National Pharmacy and Medicines Institute
Singapore: Health Sciences Authority
South Korea: Ministry of Food and Drug Safety (MFDS)
Spain: Spanish Agency of Medicines
Taiwan : Food and Drug Administration
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Erlotinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014