LUX-Lung 5: Afatinib (BIBW 2992) Plus Weekly Paclitaxel Versus Investigator's Choice of Single Agent Chemotherapy Following Afatinib Monotherapy in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01085136
First received: March 10, 2010
Last updated: October 1, 2014
Last verified: October 2014
  Purpose

The primary objective of this randomized, open-label, active-controlled, multi-center trial is to determine the efficacy of BIBW 2992 given as an add-on to chemotherapy in patients with NSCLC Stage IIIb or IV progressing after BIBW 2992 monotherapy compared to chemotherapy alone 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. Additional information on the health-related quality of life (HRQOL) will be collected.


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: Investigator´s choice of chemotherapy
Drug: BIBW 2992
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: Phase III Randomized Trial of BIBW 2992 Plus Weekly Paclitaxel Versus Investigator's Choice of Chemotherapy Following BIBW 2992 Monotherapy in Non-small Cell Lung Cancer Patients Failing Previous Erlotinib or Gefitinib Treatment (LUX Lung 5)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Progression Free Survival (PFS) Time as Determined by RECIST 1.1 for Part B. [ Time Frame: Every 8 weeks until the final follow-up visit in Part B, up to a total of 10 years. ] [ Designated as safety issue: No ]
    PFS from the day of randomisation to the day of progression according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 for patients randomised to combination therapy with afatinib plus paclitaxel or to investigators choice of chemotherapy.


Secondary Outcome Measures:
  • Progression Free Survival (PFS) as Determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 for Part A [ Time Frame: tumour assessment was at screening (-28 days to screening) and every 6 weeks until the first follow-up visit in Part A, up to a total of 10 years. ] [ Designated as safety issue: No ]
    Progression free survival (PFS) as determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 for Part A. PFS from the day of randomisation to the day of progression according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 for patients treated with Afatinib monotherapy.

  • Overall Survival (OS) as Determined by the Time From Randomization to Death in Part B [ Time Frame: from the date of randomisation to the date of death, up to a total of 10 years. ] [ Designated as safety issue: No ]
    Overall survival was calculated as the time from the date of randomisation to the date of death. Patients for whom there was no evidence of death at the time of the analysis were to be censored on the date that they were last known to have been alive.

  • Objective Response Rate According to RECIST 1.1 in Part B [ Time Frame: tumour assessment was every 8 weeks until the final follow-up visit in Part B, up to a total of 10 years. ] [ Designated as safety issue: No ]
    Objective tumour response was defined as a best overall response of complete response (CR) or partial response (PR) as determined by RECIST 1.1 and as assessed by the Investigator. For patients enrolled in Part B, a Part B best overall response was to be based on all responses taken from the start of Part B treatment until the start of any new anticancer therapy or disease progression in Part B. The duration of objective response was defined as the time of first objective response to the time of progression or death, whichever occurred first (or date of censoring for PFS).

  • Objective Response According to RECIST 1.1 in Part A [ Time Frame: tumour assessment was at screening (-28 days to screening) and every 6 weeks until the first follow-up visit in Part A, up to a total of 10 years. ] [ Designated as safety issue: No ]
    Objective tumour response was defined as a best overall response of CR or PR as determined by RECIST 1.1 and as assessed by the Investigator. For patients enrolled in Part A, this was to be based on all responses taken from the start of treatment until the start of any new anticancer therapy or disease progression. Objective response was analysed descriptively. The duration of objective response was defined as the time of first objective response to the time of progression or death, whichever occurred first (or date of censoring for PFS).


Enrollment: 1302
Study Start Date: February 2010
Estimated Study Completion Date: December 2015
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Investigator`s choice of chemotherapy
Patients will be treated with investigator`s choice of chemotherapy
Drug: Investigator´s choice of chemotherapy
BIBW 2992 in a medium dose in combination with Paclitaxel to explore safety and efficacy versus investigator´s choice of chemotherapy
Experimental: BIBW 2992 and Paclitaxel
Patients will be treated with BIBW 2992 daily with a medium dose and weekly administration of Paclitaxel at a dose of 80 mg/m2
Drug: BIBW 2992
BIBW 2992 will be given in a medium dose in combination with Paclitaxel to explore safety and efficacy versus investigator´s choice of chemotherapy

  Eligibility

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

Inclusion criteria:

Part A

  1. Patients with pathologically confirmed diagnosis of NSCLC Stage IIIB (with cytologically proven pleural effusion or pericardial effusion) or Stage IV who have failed treatment with erlotinib (Tarceva) or gefitinib (Iressa).
  2. Patients should have received and failed at least one line of cytotoxic chemotherapy including a platinum-based regimen in patients eligible for platinum-based therapy and pemetrexed in pemetrexed eligible patients (unless pemetrexed is not considered a regulatory or clinical standard of care e.g. no label indication, no availability or no coverage by 3rd party payer(s)) for advanced or metastatic disease and have progressive disease following at least 12 weeks of treatment with erlotinib or gefitinib
  3. Patients pretreated with taxane-based chemotherapy for advanced or metastatic disease must have experienced stable disease, partial or complete response as best response
  4. Eastern Cooperative Oncology Group performance Score 0 or 1.
  5. 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 10 mm but no less than double the slice thickness according to RESIST 1.1.
  6. Male and female patients no less than 18 years of age.
  7. Life expectancy of at least three (3) months.
  8. Written informed consent that is consistent with ICH-GCP guidelines. Part B 1) Clinical benefit (disease stabilization or antitumor response) of 12 weeks duration in Part A of the trial determined on the second tumour assessment.

2.) Patients should have progressed in Part A according to RECIST 1.1 3.) New informed consent, including consent to biomarker sampling, must be signed before patients enter Part B of the trial

Exclusion criteria:

  1. Chemo-, hormone- (other than megestrol acetate, steroids required for maintenance non-cancer therapy or as premedication before chemotherapy) or immunotherapy within the past 4 weeks; except for TKI pretreatment (2 weeks only)
  2. Active/symptomatic brain metastases including leptomeningeal disease. Patients with a history of treated brain metastasis must have a stable or normal brain MRT/CT scan at screening and be at least 4 weeks post-radiation or surgery for brain metastasis. Dexamethasone therapy will be allowed if administered as a stable dose for at least one month before randomization.
  3. Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn's disease, mal-absorption, or CTCAE Grade >2 diarrhea of any etiology at baseline
  4. Patients who have any other life-threatening 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
  5. Other malignancies diagnosed within the past five (5) years (other than non-melanomatous skin cancer and in situ cervical cancer)
  6. Radiotherapy within the past 2 weeks prior to treatment with the trial drug
  7. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) functional classification of 3, unstable angina, or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to randomization.
  8. Cardiac left ventricular function with resting ejection fraction of less than 50% measured by multigated blood pool imaging of the heart (MUGA scan) or echocardiogram
  9. Requirement for treatment with any of the prohibited concomitant medications listed in section 4.2.2.1
  10. Prior treatment with anthracyclines with a cumulative dose of doxorubicin (or equivalent) at or greater than 400 mg/m2
  11. Absolute neutrophil count (ANC) at or less than 1500 / mm3
  12. Platelet count at or less than 100,000 / mm3
  13. Bilirubin at or greater than 1.5 mg / dL (>26 mol / L, SI unit equivalent)
  14. Aspartate amino transferase (AST) or alanine amino transferase (ALT) at or greater than three times the upper limit of normal (if related to liver metastases at or greater than five times the upper limit of normal)
  15. Serum creatinine at or greater 1.5 times the upper normal limit or calculated/measured creatinine clearance at or less than 45 mL/min
  16. Women of child-bearing potential or men who are able to father a child unwilling to use a medically acceptable method of contraception during the trial
  17. Pregnancy or breast feeding
  18. Patients unable to comply with the protocol
  19. Patients with any serious active infection including known human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C
  20. Known or suspected active drug or alcohol abuse
  21. Pre-existing or current Interstitial lung disease (ILD) 22.) Peripheral polyneuropathy of > Grade 2
  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: NCT01085136

  Hide Study Locations
Locations
Argentina
1200.42.54006 Boehringer Ingelheim Investigational Site
Ciudad Autonoma de Buenos Aires, Argentina
Australia, New South Wales
1200.42.61004 Boehringer Ingelheim Investigational Site
Kingswood, New South Wales, Australia
Australia, Queensland
1200.42.61005 Boehringer Ingelheim Investigational Site
South Brisbane, Queensland, Australia
Australia, Victoria
1200.42.61002 Boehringer Ingelheim Investigational Site
Box Hill, Victoria, Australia
1200.42.61001 Boehringer Ingelheim Investigational Site
Fitzroy, Victoria, Australia
1200.42.61003 Boehringer Ingelheim Investigational Site
Wodonga, Victoria, Australia
Austria
1200.42.43002 Boehringer Ingelheim Investigational Site
Salzburg, Austria
Belgium
1200.42.32007 Boehringer Ingelheim Investigational Site
Aalst, Belgium
1200.42.32001 Boehringer Ingelheim Investigational Site
Bruxelles, Belgium
1200.42.32006 Boehringer Ingelheim Investigational Site
Duffel, Belgium
1200.42.32004 Boehringer Ingelheim Investigational Site
La Louvière, Belgium
1200.42.32002 Boehringer Ingelheim Investigational Site
Liège, Belgium
1200.42.32005 Boehringer Ingelheim Investigational Site
Middelheim, Belgium
1200.42.32003 Boehringer Ingelheim Investigational Site
Ottignies, Belgium
Brazil
1200.42.55004 Boehringer Ingelheim Investigational Site
Porto Alegre, Brazil
China
1200.42.86007 Boehringer Ingelheim Investigational Site
Beijing, China
1200.42.86008 Boehringer Ingelheim Investigational Site
Changchun, China
1200.42.86003 Boehringer Ingelheim Investigational Site
Chengdu, China
1200.42.86005 Boehringer Ingelheim Investigational Site
Fuzhou, China
1200.42.86004 Boehringer Ingelheim Investigational Site
Fuzhou, China
1200.42.86006 Boehringer Ingelheim Investigational Site
Guangzhou, China
1200.42.86012 Boehringer Ingelheim Investigational Site
Hangzhou, China
1200.42.86011 Boehringer Ingelheim Investigational Site
Hangzhou, China
1200.42.86010 Boehringer Ingelheim Investigational Site
Nanjing, China
1200.42.86009 Boehringer Ingelheim Investigational Site
Nanjing, China
1200.42.86002 Boehringer Ingelheim Investigational Site
Shanghai, China
1200.42.86013 Boehringer Ingelheim Investigational Site
Shanghai, China
Finland
1200.42.35801 Boehringer Ingelheim Investigational Site
Helsinki, Finland
1200.42.35802 Boehringer Ingelheim Investigational Site
Helsinki, Finland
France
1200.42.33013 Boehringer Ingelheim Investigational Site
Bayonne, France
1200.42.33003 Boehringer Ingelheim Investigational Site
Caen Cedex 5, France
1200.42.33011 Boehringer Ingelheim Investigational Site
Caen cedex 5, France
1200.42.33010 Boehringer Ingelheim Investigational Site
Dijon, France
1200.42.33004 Boehringer Ingelheim Investigational Site
La Tronche, France
1200.42.33005 Boehringer Ingelheim Investigational Site
Lyon Cedex 08, France
1200.42.33002 Boehringer Ingelheim Investigational Site
Paris, France
1200.42.33001 Boehringer Ingelheim Investigational Site
Paris cedex 20, France
1200.42.33007 Boehringer Ingelheim Investigational Site
Saint-Herblain cedex, France
1200.42.33006 Boehringer Ingelheim Investigational Site
Villejuif Cedex, France
Germany
1200.42.49002 Boehringer Ingelheim Investigational Site
Berlin, Germany
1200.42.49001 Boehringer Ingelheim Investigational Site
Essen, Germany
1200.42.49013 Boehringer Ingelheim Investigational Site
Esslingen, Germany
1200.42.49003 Boehringer Ingelheim Investigational Site
Gauting, Germany
1200.42.49014 Boehringer Ingelheim Investigational Site
Hamburg, Germany
1200.42.49006 Boehringer Ingelheim Investigational Site
Hannover, Germany
1200.42.49007 Boehringer Ingelheim Investigational Site
Heidelberg, Germany
1200.42.49009 Boehringer Ingelheim Investigational Site
Mainz, Germany
1200.42.49010 Boehringer Ingelheim Investigational Site
Münster, Germany
Hungary
1200.42.36004 Boehringer Ingelheim Investigational Site
Budapest, Hungary
1200.42.36005 Boehringer Ingelheim Investigational Site
Pecs, Hungary
1200.42.36001 Boehringer Ingelheim Investigational Site
Törökbálint, Hungary
India
1200.42.91003 Boehringer Ingelheim Investigational Site
Chennai, India
1200.42.91004 Boehringer Ingelheim Investigational Site
Jaipur, India
1200.42.91002 Boehringer Ingelheim Investigational Site
Maharashtra, India
1200.42.91001 Boehringer Ingelheim Investigational Site
Mumbai, India
1200.42.91006 Boehringer Ingelheim Investigational Site
Nashik, Maharashtra, India
Israel
1200.42.97203 Boehringer Ingelheim Investigational Site
Kfar Saba, Israel
1200.42.97204 Boehringer Ingelheim Investigational Site
Petach Tikva, Israel
1200.42.97201 Boehringer Ingelheim Investigational Site
Tel Hashomer, Israel
Italy
1200.42.39005 Boehringer Ingelheim Investigational Site
Avellino, Italy
1200.42.39004 Boehringer Ingelheim Investigational Site
Aviano (PN), Italy
1200.42.39008 Boehringer Ingelheim Investigational Site
Bergamo, Italy
1200.42.39002 Boehringer Ingelheim Investigational Site
Genova, Italy
1200.42.39007 Boehringer Ingelheim Investigational Site
Milano, Italy
1200.42.39003 Boehringer Ingelheim Investigational Site
Monza (mi), Italy
1200.42.39009 Boehringer Ingelheim Investigational Site
Ravenna, Italy
1200.42.39001 Boehringer Ingelheim Investigational Site
Roma, Italy
Korea, Republic of
1200.42.82005 Boehringer Ingelheim Investigational Site
Goyang, Korea, Republic of
1200.42.82006 Boehringer Ingelheim Investigational Site
Hwasun, Korea, Republic of
1200.42.82004 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1200.42.82003 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1200.42.82001 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1200.42.82002 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
Mexico
1200.42.52003 Boehringer Ingelheim Investigational Site
Distrito Federal, Mexico
Netherlands
1200.42.31005 Boehringer Ingelheim Investigational Site
Maastricht, Netherlands
1200.42.31006 Boehringer Ingelheim Investigational Site
Nieuwegein, Netherlands
Peru
1200.42.51002 Boehringer Ingelheim Investigational Site
Arequipa, Peru
1200.42.51001 Boehringer Ingelheim Investigational Site
La Victoria, Peru
Poland
1200.42.48006 Boehringer Ingelheim Investigational Site
Gdansk, Poland
1200.42.48002 Boehringer Ingelheim Investigational Site
Olsztyn, Poland
1200.42.48004 Boehringer Ingelheim Investigational Site
Otwock, Poland
1200.42.48001 Boehringer Ingelheim Investigational Site
Warszawa, Poland
Russian Federation
1200.42.70006 Boehringer Ingelheim Investigational Site
Obninsk, Russian Federation
1200.42.70005 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
1200.42.70004 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
Spain
1200.42.34005 Boehringer Ingelheim Investigational Site
A Coruña, Spain
1200.42.34008 Boehringer Ingelheim Investigational Site
Barcelona, Spain
1200.42.34002 Boehringer Ingelheim Investigational Site
Madrid, Spain
1200.42.34001 Boehringer Ingelheim Investigational Site
Madrid, Spain
1200.42.34006 Boehringer Ingelheim Investigational Site
Mataró, Spain
1200.42.34007 Boehringer Ingelheim Investigational Site
Málaga, Spain
1200.42.34003 Boehringer Ingelheim Investigational Site
Valencia, Spain
Taiwan
1200.42.88608 Boehringer Ingelheim Investigational Site
Kaohsiung, Taiwan
1200.42.88606 Boehringer Ingelheim Investigational Site
Taichung, Taiwan
1200.42.88605 Boehringer Ingelheim Investigational Site
Taichung, Taiwan
1200.42.88602 Boehringer Ingelheim Investigational Site
Taichung, Taiwan
1200.42.88607 Boehringer Ingelheim Investigational Site
Tainan, Taiwan
1200.42.88609 Boehringer Ingelheim Investigational Site
Taipei, Taiwan
1200.42.88601 Boehringer Ingelheim Investigational Site
Taipei, Taiwan
1200.42.88603 Boehringer Ingelheim Investigational Site
Taipei, Taiwan
1200.42.88610 Boehringer Ingelheim Investigational Site
Taipei, Taiwan
1200.42.88604 Boehringer Ingelheim Investigational Site
Taoyuan, Taiwan
Ukraine
1200.42.38004 Boehringer Ingelheim Investigational Site
Dnipropetrovks, Ukraine
1200.42.38002 Boehringer Ingelheim Investigational Site
Donetsk, Ukraine
1200.42.38001 Boehringer Ingelheim Investigational Site
Kharkiv, Ukraine
1200.42.38003 Boehringer Ingelheim Investigational Site
Kyiv, Ukraine
United Kingdom
1200.42.44003 Boehringer Ingelheim Investigational Site
Brighton, United Kingdom
1200.42.44005 Boehringer Ingelheim Investigational Site
Dundee, United Kingdom
1200.42.44007 Boehringer Ingelheim Investigational Site
Exeter, United Kingdom
1200.42.44004 Boehringer Ingelheim Investigational Site
London, United Kingdom
1200.42.44006 Boehringer Ingelheim Investigational Site
London, United Kingdom
1200.42.44001 Boehringer Ingelheim Investigational Site
Maidstone, United Kingdom
1200.42.44012 Boehringer Ingelheim Investigational Site
Manchester, United Kingdom
1200.42.44008 Boehringer Ingelheim Investigational Site
Sutton, Surrey, United Kingdom
1200.42.44011 Boehringer Ingelheim Investigational Site
Truro, Cornwall, United Kingdom
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: NCT01085136     History of Changes
Other Study ID Numbers: 1200.42, 2009-014563-39
Study First Received: March 10, 2010
Results First Received: October 1, 2014
Last Updated: October 1, 2014
Health Authority: Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica
Australia: Dept of Health and Ageing Therapeutic Goods Admin
Austria: Medicines and Medical Devices Agency
Belgium: Federal Agency for Medicinal and Health Products
Brazil: National Health Surveillance Agency
China: Food and Drug Administration
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: Ethics Committee
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: Central Committee Research Involving Human Subjects
Peru: Ministry of Health
Poland: Registration Medicinal Product Medical Device Biocidal Product
Russia: Pharmacological Committee, Ministry of Health
South Korea: Ministry of Food and Drug Safety (MFDS)
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
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
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 22, 2014