LUX-Lung 5: Afatinib 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 has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01085136
First received: March 10, 2010
Last updated: April 2, 2014
Last verified: April 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 time as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) from day of randomization until progression for patients randomized to either BIBW 2992/paclitaxel combination therapy or comparator chemotherapy. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression free survival (PFS) as determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 for Part A [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival (OS) as determined by the time from randomization to death in part B [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Objective response rate (complete response [CR], partial response [PR]) of BIBW 2992 monotherapy according to RECIST 1.1 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Objective response rate (CR, PR) of BIBW 2992/paclitaxel combination therapy and comparator chemotherapy in Part B after in Part A according to RECIST 1.1 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Safety of BIBW 2992 as indicated by intensity and incidence of adverse events, graded according to United States National Cancer Institute Common terminology Criteria for Adverse Events (US NCI CTCAE) Version 3.0 both for Part A and Part B. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 1155
Study Start Date: February 2010
Study Completion Date: November 2013
Primary Completion Date: November 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 2992daily 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01085136

  Show 115 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More 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
Last Updated: April 2, 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
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Paclitaxel
Gefitinib
Erlotinib
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014