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
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01085136 |
Recruitment Status :
Completed
First Posted : March 11, 2010
Results First Posted : October 3, 2014
Last Update Posted : April 4, 2017
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Carcinoma, Non-Small-Cell Lung | Drug: Investigator´s choice of chemotherapy Drug: BIBW 2992 | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 1154 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (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) |
Study Start Date : | February 2010 |
Actual Primary Completion Date : | October 2013 |
Actual Study Completion Date : | January 2016 |
Arm | Intervention/treatment |
---|---|
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 |
- Progression Free Survival (Part B) [ Time Frame: From randomization until disease progression or death; Up to 32 months ]
Progression free survival (PFS) time as determined by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 from day of randomization until disease progression or death for patients randomised to combination therapy with afatinib plus paclitaxel or to investigator's choice of chemotherapy.
Median was calculated from the Kaplan-Meier curve.
- Progression Free Survival (Part A) [ Time Frame: From first dose administration until disease progression or death; Up to 51 months ]
Progression free survival (PFS) as determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 for Part A.
Median was calculated from the Kaplan-Meier curve.
- Overall Survival (Part B) [ Time Frame: From randomization until death; Up to 32 months ]
Overall survival (OS) as determined by the time from randomization to death in part B.
Median was calculated from the Kaplan-Meier curve.
- Objective Response (Part A) [ Time Frame: Post baseline tumour-imaging was performed at every 6 weeks thereafter until disease progression; upto 51 months ]Objective response defined as the best overall response of complete response [CR]: disappearance of all target lesion & partial response [PR]: ≥30% decrease in the sum of the longest diameter of target lesions , taking as reference the baseline sum longest diameter of Afatinib monotherapy according to RECIST 1.1 for Part A.
- Objective Response (Part B) [ Time Frame: Post baseline tumour-imaging was performed at every 8 weeks thereafter until disease progression; up to 32 Months ]Objective response (CR, PR) of Afatinib/paclitaxel combination therapy and comparator chemotherapy in Part B after progression in Part A according to RECIST 1.1 .
- Intensity and Incidence of Adverse Events (AEs) for Part A & Part B. [ Time Frame: From first administration of treatment until 28 days after last drug administration, up to 51 Months (Part A) and from randomization until 28 days after last drug administration of Trial medication, up to 32 Months (Part B) ]Safety of Afatinib 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. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
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, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion criteria:
Part A
- 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).
- 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
- Patients pretreated with taxane-based chemotherapy for advanced or metastatic disease must have experienced stable disease, partial or complete response as best response
- Eastern Cooperative Oncology Group performance Score 0 or 1.
- 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.
- Male and female patients no less than 18 years of age.
- Life expectancy of at least three (3) months.
- 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:
- Previous treatment with BIBW 2992
- 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)
- 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.
- 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
- 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
- Other malignancies diagnosed within the past five (5) years (other than non-melanomatous skin cancer and in situ cervical cancer)
- Radiotherapy within the past 2 weeks prior to treatment with the trial drug
- 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 entering the trial.
- 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 .
- Prior treatment with anthracyclines with a cumulative dose of doxorubicin (or equivalent) at or greater than 400 mg/m2
- Absolute neutrophil count (ANC) at or less than 1500 / mm3
- Platelet count at or less than 100,000 / mm3
- Bilirubin at or greater than 1.5 mg / dL (>26 mol / L, SI unit equivalent)
- 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)
- Serum creatinine at or greater 1.5 times the upper normal limit or calculated/measured creatinine clearance at or less than 45 mL/min
- 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
- Pregnancy or breast feeding
- Patients unable to comply with the protocol
- Patients with any serious active infection including known human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C
- Known or suspected active drug or alcohol abuse
- Pre-existing or current Interstitial lung disease (ILD) 22.)
- Peripheral polyneuropathy of > Grade 2
- Requirement for treatment with any of the pohibited concomitant medication listed in section 4.2.2.1.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01085136
Study Chair: | Boehringer Ingelheim | Boehringer Ingelheim |
Responsible Party: | Boehringer Ingelheim |
ClinicalTrials.gov Identifier: | NCT01085136 |
Other Study ID Numbers: |
1200.42 2009-014563-39 ( EudraCT Number: EudraCT ) |
First Posted: | March 11, 2010 Key Record Dates |
Results First Posted: | October 3, 2014 |
Last Update Posted: | April 4, 2017 |
Last Verified: | February 2017 |
Carcinoma, Non-Small-Cell Lung Carcinoma, Bronchogenic Bronchial Neoplasms Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms |
Lung Diseases Respiratory Tract Diseases Afatinib Tyrosine Kinase Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |