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

February 15, 2017 updated by: Boehringer Ingelheim

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)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1154

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Ciudad Autonoma de Buenos Aires, Argentina
        • Boehringer Ingelheim Investigational Site
  • Australia
    • New South Wales
      • Kingswood, New South Wales, Australia
        • Boehringer Ingelheim Investigational Site
    • Queensland
      • South Brisbane, Queensland, Australia
        • Boehringer Ingelheim Investigational Site
    • Victoria
      • Box Hill, Victoria, Australia
        • Boehringer Ingelheim Investigational Site
      • Fitzroy, Victoria, Australia
        • Boehringer Ingelheim Investigational Site
      • Wodonga, Victoria, Australia
        • Boehringer Ingelheim Investigational Site
  • Austria
      • Salzburg, Austria
        • Boehringer Ingelheim Investigational Site
  • Belgium
      • Aalst, Belgium
        • Boehringer Ingelheim Investigational Site
      • Bruxelles, Belgium
        • Boehringer Ingelheim Investigational Site
      • Duffel, Belgium
        • Boehringer Ingelheim Investigational Site
      • La Louvière, Belgium
        • Boehringer Ingelheim Investigational Site
      • Liège, Belgium
        • Boehringer Ingelheim Investigational Site
      • Middelheim, Belgium
        • Boehringer Ingelheim Investigational Site
      • Ottignies, Belgium
        • Boehringer Ingelheim Investigational Site
  • Brazil
      • Porto Alegre, Brazil
        • Boehringer Ingelheim Investigational Site
  • China
      • Beijing, China
        • Boehringer Ingelheim Investigational Site
      • Changchun, China
        • Boehringer Ingelheim Investigational Site
      • Chengdu, China
        • Boehringer Ingelheim Investigational Site
      • Fuzhou, China
        • Boehringer Ingelheim Investigational Site
      • Guangzhou, China
        • Boehringer Ingelheim Investigational Site
      • Hangzhou, China
        • Boehringer Ingelheim Investigational Site
      • Nanjing, China
        • Boehringer Ingelheim Investigational Site
      • Shanghai, China
        • Boehringer Ingelheim Investigational Site
  • Finland
      • Helsinki, Finland
        • Boehringer Ingelheim Investigational Site
  • France
      • Bayonne, France
        • Boehringer Ingelheim Investigational Site
      • Caen Cedex 5, France
        • Boehringer Ingelheim Investigational Site
      • Dijon, France
        • Boehringer Ingelheim Investigational Site
      • La Tronche, France
        • Boehringer Ingelheim Investigational Site
      • Lyon Cedex 08, France
        • Boehringer Ingelheim Investigational Site
      • Paris, France
        • Boehringer Ingelheim Investigational Site
      • Paris cedex 20, France
        • Boehringer Ingelheim Investigational Site
      • Saint-Herblain cedex, France
        • Boehringer Ingelheim Investigational Site
      • Villejuif Cedex, France
        • Boehringer Ingelheim Investigational Site
  • Germany
      • Berlin, Germany
        • Boehringer Ingelheim Investigational Site
      • Essen, Germany
        • Boehringer Ingelheim Investigational Site
      • Esslingen, Germany
        • Boehringer Ingelheim Investigational Site
      • Gauting, Germany
        • Boehringer Ingelheim Investigational Site
      • Hamburg, Germany
        • Boehringer Ingelheim Investigational Site
      • Hannover, Germany
        • Boehringer Ingelheim Investigational Site
      • Heidelberg, Germany
        • Boehringer Ingelheim Investigational Site
      • Mainz, Germany
        • Boehringer Ingelheim Investigational Site
      • Münster, Germany
        • Boehringer Ingelheim Investigational Site
  • Hungary
      • Budapest, Hungary
        • Boehringer Ingelheim Investigational Site
      • Pecs, Hungary
        • Boehringer Ingelheim Investigational Site
      • Törökbálint, Hungary
        • Boehringer Ingelheim Investigational Site
  • India
      • Chennai, India
        • Boehringer Ingelheim Investigational Site
      • Jaipur, India
        • Boehringer Ingelheim Investigational Site
      • Maharashtra, India
        • Boehringer Ingelheim Investigational Site
      • Mumbai, India
        • Boehringer Ingelheim Investigational Site
      • Nashik, Maharashtra, India
        • Boehringer Ingelheim Investigational Site
  • Israel
      • Kfar Saba, Israel
        • Boehringer Ingelheim Investigational Site
      • Petach Tikva, Israel
        • Boehringer Ingelheim Investigational Site
      • Tel Hashomer, Israel
        • Boehringer Ingelheim Investigational Site
  • Italy
      • Avellino, Italy
        • Boehringer Ingelheim Investigational Site
      • Aviano (PN), Italy
        • Boehringer Ingelheim Investigational Site
      • Bergamo, Italy
        • Boehringer Ingelheim Investigational Site
      • Genova, Italy
        • Boehringer Ingelheim Investigational Site
      • Milano, Italy
        • Boehringer Ingelheim Investigational Site
      • Monza (mi), Italy
        • Boehringer Ingelheim Investigational Site
      • Ravenna, Italy
        • Boehringer Ingelheim Investigational Site
      • Roma, Italy
        • Boehringer Ingelheim Investigational Site
  • Korea, Republic of
      • Goyang, Korea, Republic of
        • Boehringer Ingelheim Investigational Site
      • Hwasun, Korea, Republic of
        • Boehringer Ingelheim Investigational Site
      • Seoul, Korea, Republic of
        • Boehringer Ingelheim Investigational Site
  • Mexico
      • Distrito Federal, Mexico
        • Boehringer Ingelheim Investigational Site
  • Netherlands
      • Maastricht, Netherlands
        • Boehringer Ingelheim Investigational Site
      • Nieuwegein, Netherlands
        • Boehringer Ingelheim Investigational Site
  • Peru
      • Arequipa, Peru
        • Boehringer Ingelheim Investigational Site
      • La Victoria, Peru
        • Boehringer Ingelheim Investigational Site
  • Poland
      • Gdansk, Poland
        • Boehringer Ingelheim Investigational Site
      • Olsztyn, Poland
        • Boehringer Ingelheim Investigational Site
      • Otwock, Poland
        • Boehringer Ingelheim Investigational Site
      • Warszawa, Poland
        • Boehringer Ingelheim Investigational Site
  • Russian Federation
      • Obninsk, Russian Federation
        • Boehringer Ingelheim Investigational Site
      • St. Petersburg, Russian Federation
        • Boehringer Ingelheim Investigational Site
  • Spain
      • A Coruña, Spain
        • Boehringer Ingelheim Investigational Site
      • Barcelona, Spain
        • Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • Boehringer Ingelheim Investigational Site
      • Mataró, Spain
        • Boehringer Ingelheim Investigational Site
      • Málaga, Spain
        • Boehringer Ingelheim Investigational Site
      • Valencia, Spain
        • Boehringer Ingelheim Investigational Site
  • Taiwan
      • Kaohsiung, Taiwan
        • Boehringer Ingelheim Investigational Site
      • Taichung, Taiwan
        • Boehringer Ingelheim Investigational Site
      • Tainan, Taiwan
        • Boehringer Ingelheim Investigational Site
      • Taipei, Taiwan
        • Boehringer Ingelheim Investigational Site
      • Taoyuan, Taiwan
        • Boehringer Ingelheim Investigational Site
  • Ukraine
      • Dnipropetrovks, Ukraine
        • Boehringer Ingelheim Investigational Site
      • Donetsk, Ukraine
        • Boehringer Ingelheim Investigational Site
      • Kharkiv, Ukraine
        • Boehringer Ingelheim Investigational Site
      • Kyiv, Ukraine
        • Boehringer Ingelheim Investigational Site
  • United Kingdom
      • Brighton, United Kingdom
        • Boehringer Ingelheim Investigational Site
      • Dundee, United Kingdom
        • Boehringer Ingelheim Investigational Site
      • Exeter, United Kingdom
        • Boehringer Ingelheim Investigational Site
      • London, United Kingdom
        • Boehringer Ingelheim Investigational Site
      • Maidstone, United Kingdom
        • Boehringer Ingelheim Investigational Site
      • Manchester, United Kingdom
        • Boehringer Ingelheim Investigational Site
      • Sutton, Surrey, United Kingdom
        • Boehringer Ingelheim Investigational Site
      • Truro, Cornwall, United Kingdom
        • Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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. Previous treatment with BIBW 2992
  2. 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)
  3. 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.
  4. 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
  5. 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
  6. Other malignancies diagnosed within the past five (5) years (other than non-melanomatous skin cancer and in situ cervical cancer)
  7. Radiotherapy within the past 2 weeks prior to treatment with the trial drug
  8. 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.
  9. 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 .
  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.)
  22. Peripheral polyneuropathy of > Grade 2
  23. Requirement for treatment with any of the pohibited concomitant medication listed in section 4.2.2.1.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
From randomization until disease progression or death; Up to 32 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
From first dose administration until disease progression or death; Up to 51 months
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.
From randomization until death; Up to 32 months
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.
Post baseline tumour-imaging was performed at every 6 weeks thereafter until disease progression; upto 51 months
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 .
Post baseline tumour-imaging was performed at every 8 weeks thereafter until disease progression; up to 32 Months
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).
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 10, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 11, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 4, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 15, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1200.42
  • 2009-014563-39 (EudraCT Number: EudraCT)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Carcinoma, Non-Small-Cell Lung

Clinical Trials on Investigator´s choice of chemotherapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings