Carcinoma, Non-Small-Cell LungPhase 2NCT00730925
Single-arm Trial of BIBW 2992 (Afatinib) in Demographically and Genotypically Selected NSCLC Patients
A Phase 2 study testing BIBW2992 and BIBW2992 + paclitaxel in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 7 sites in 2 countries.
Trial summary
The primary objective of this open-label, single arm Phase II trial is to explore the efficacy of BIBW 2992 defined by the objective response rate (CR, PR) as determined by the RECIST criteria, in patients with advanced NSCLC Stage IIIB or IV whose tumours harbour activating mutations within exon 18 to exon 21 of the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- BIBW2992 and BIBW2992 + paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Jun 2008to Jan 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients with pathologically confirmed diagnosis of NSCLC stage IIIB/IV adeno- or bronchoalveolar carcinoma (BAC)
- non smokers patients or patients having smoked less than 15 pack years and who stopped smoking for at least one year before diagnosis (except for patients with her2-neu mutation)
- presence of activating mutation(s) in exon 18 to exon 21 of the EGFR or HER2-neu-receptor confirmed by direct DNA sequencing of NSCLC tumor tissue or increased copy number of the EGFR gene as determined by FISH analysis
- prior treatment up to 3 lines of chemotherapy except for HER2-neu patients (no restrictions) no prior EGFR TKI therapy for EGFR mutation negative and FISCH positive patients
- patients with at least one tumor lesion that can accurately be measured by CTscan or MRI in at least one dimension with long diameter to be recorded as > or equal to 20 mm using conventional techniques or > or equal to 10 mm with spiral CT scan
- male or female patient aged above or equal to 18 years
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- life expectancy of at least 3 months
- written informed consents that is consistent with ICH-GCP guidelines
- ECOG performance score 0, 1 or 2
Who cannot join
- more than 3 prior cytotoxic chemotherapy treatment regimen for relapsed or metastatic NSCLC, except for patients with HER2-neu mutations who may have received any prior therapy
- Any chemo-, hormone- or immunotherapy within the past 4 weeks or within less than 4 half-lives of the previous drug prior to treatment with the trial drug and/or persistence of toxicities of prior anticancer therapies which are deemed to be clinically relevant
- brain metastases which are symptomatic; patients with treated asymptomatic brain metastases are eligible with stable brain disease for at least 4 weeks without requirement for steroids or anti-epileptic therapy
- significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g. Crohn's disease, malabsorption 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 5 years (other than non melanomatous skin cancer and in situ cervical cancer)
Show all 20Show fewer
- radiotherapy within the past 2 weeks prior to treatment with the trial drug
- patients with any serious active infection (i.e., requiring an IV antibiotic, antifungal, or antiviral agents)
- patients with known HIV, active hepatitis B or active hepatitis C
- known or suspected active drug or alcohol abuse
- women of childbearing 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
- patient unable to comply with the protocol
- history of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, including New York Heart Association (NYHA) functional classification of 3
- 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.
- Absolute neutrophil count (ANC) less than 1500/mm³.
- Platelet count less than 100 000 / mm³.
- Bilirubin greater than 1.5 mg / dl (>26 µmol / L, SI unit equivalent).
- Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than three times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal).
- Serum creatinine greater than 1.5 times of the upper normal limit
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Belgium6 sites
1200.41.32003 Boehringer Ingelheim Investigational Site
Antwerp
1200.41.32007 Boehringer Ingelheim Investigational Site
Charleroi
1200.41.32001 Boehringer Ingelheim Investigational Site
Jette
1200.41.32011 Boehringer Ingelheim Investigational Site
Leuven
1200.41.32008 Boehringer Ingelheim Investigational Site
Liège
1200.41.32006 Boehringer Ingelheim Investigational Site
Namur
Spain1 site
1200.41.34001 Boehringer Ingelheim Investigational Site
Badalona (Barcelona)
About this study
Official title: A Phase II Single-arm Trial of BIBW 2992 in Demographically and Genotypically Selected NSCLC
The primary objective of this open-label, single arm Phase II trial is to explore the efficacy of BIBW 2992 defined by the objective response rate (CR, PR) as determined by the RECIST criteria, in patients with advanced NSCLC Stage IIIB or IV whose tumours harbour activating mutations within exon 18 to exon 21 of the EGFR receptor, in patients with mutations in the HER2/neu receptor and in patients with EGFR FISH positive tumours with no EGFR mutations.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- BIBW2992, BIBW2992 + paclitaxel
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIBW2992Drug
tablet BIBW high dose
BIBW2992 + paclitaxelDrug
tablet BIBW 2992 in combination with i.v. paclitaxel 3 weekly
| Study group | Role | What they receive |
|---|---|---|
| BIBW 2992 | Experimental | patient to receive tablets of BIBW 2992 once a day, starting at high dose until progression of the disease Receives: Drug: BIBW2992 |
| BIBW 2992 + paclitaxel | Experimental | patient whose disease progressed on treatment with BIBW 2992 monotherapy to receive tablet of BIBW 2992 once a day in combination with i.v. paclitaxel 3 weekly Receives: Drug: BIBW2992 + paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Best Objective Response
Percentage of participants with best objective response: confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.0.
Measured: Tumour assessments were performed at baseline (tumour assessment obtained within 4 weeks prior to beginning of treatment), week 8, and every 8 weeks thereafter.
Secondary outcomes (3)
Percentage of Participants With Disease Control (DC)
Percentage of participants with OR or stable disease (SD) as determined by RECIST version 1.0.
Measured: Tumour assessments were performed at baseline (tumour assessment obtained within 4 weeks prior to beginning of treatment), week 8, and every 8 weeks thereafter.
Progression Free Survival (PFS) Time
PFS time defined as time from the start of treatment to the earliest of progression (RECIST), clinical progression (investigator), start of new anti-cancer treatment or death.
Measured: Tumour assessments were performed at baseline (tumour assessment obtained within 4 weeks prior to beginning of treatment), week 8, and every 8 weeks thereafter.
Summary of Pre-dose Concentrations of Afatnib in Plasma
Pre-dose Concentrations of Afatinib in Plasma at Steady State on Days 15, 29 and 57 (Cpre,ss,15, Cpre,ss,29 and Cpre,ss,57)
Measured: Day 15, 29 and 57
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2008 (estimated)
- Study startJun 2008
- Primary completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00730925
- Sponsor's protocol ID
- 1200.41
- Other IDs
- 2008-001546-67, 2008
- Status last verified
- Feb 2014
- First submitted
- 30 Jun 2008
- Last updated
- 26 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
De Greve J, Teugels E, Geers C, Decoster L, Galdermans D, De Mey J, Everaert H, Umelo I, In't Veld P, Schallier D. Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu. Lung Cancer. 2012 Apr;76(1):123-7. doi: 10.1016/j.lungcan.2012.01.008. Epub 2012 Feb 10.
PubMed 22325357
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Single-arm Trial of BIBW 2992 in Demographically and Genotypically Selected NSCLC
- ClinicalTrials.gov ID
- NCT00730925
- Acronym / sponsor ID
- 1200.41
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Jun 2008
- Primary completion
- Jan 2012 (actual)
- First posted
- 8 Aug 2008 (estimated)
- Results
- Posted 23 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this open-label, single arm Phase II trial is to explore the efficacy of BIBW 2992 defined by the objective response rate (CR, PR) as determined by the RECIST criteria, in patients with advanced NSCLC Stage IIIB or IV whose tumours harbour activating mutations within exon 18 to exon 21 of the EGFR receptor, in patients with mutations in the HER2/neu receptor and in patients with EGFR FISH positive tumours with no EGFR mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BIBW 2992 | Experimental | Drug: BIBW2992patient to receive tablets of BIBW 2992 once a day, starting at high dose until progression of the disease |
| BIBW 2992 + paclitaxel | Experimental | Drug: BIBW2992 + paclitaxelpatient whose disease progressed on treatment with BIBW 2992 monotherapy to receive tablet of BIBW 2992 once a day in combination with i.v. paclitaxel 3 weekly |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- patients with pathologically confirmed diagnosis of NSCLC stage IIIB/IV adeno- or bronchoalveolar carcinoma (BAC)
- non smokers patients or patients having smoked less than 15 pack years and who stopped smoking for at least one year before diagnosis (except for patients with her2-neu mutation)
- presence of activating mutation(s) in exon 18 to exon 21 of the EGFR or HER2-neu-receptor confirmed by direct DNA sequencing of NSCLC tumor tissue or increased copy number of the EGFR gene as determined by FISH analysis
- prior treatment up to 3 lines of chemotherapy except for HER2-neu patients (no restrictions) no prior EGFR TKI therapy for EGFR mutation negative and FISCH positive patients
- patients with at least one tumor lesion that can accurately be measured by CTscan or MRI in at least one dimension with long diameter to be recorded as > or equal to 20 mm using conventional techniques or > or equal to 10 mm with spiral CT scan
Key exclusion criteria (20 listed)
- more than 3 prior cytotoxic chemotherapy treatment regimen for relapsed or metastatic NSCLC, except for patients with HER2-neu mutations who may have received any prior therapy
- Any chemo-, hormone- or immunotherapy within the past 4 weeks or within less than 4 half-lives of the previous drug prior to treatment with the trial drug and/or persistence of toxicities of prior anticancer therapies which are deemed to be clinically relevant
- brain metastases which are symptomatic; patients with treated asymptomatic brain metastases are eligible with stable brain disease for at least 4 weeks without requirement for steroids or anti-epileptic therapy
- significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g. Crohn's disease, malabsorption 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BIBW2992tablet BIBW high dose | Drug | BIBW 2992 |
| BIBW2992 + paclitaxeltablet BIBW 2992 in combination with i.v. paclitaxel 3 weekly | Drug | BIBW 2992 + paclitaxel |
Primary outcome
Percentage of Participants With Best Objective Response
Time frame: Tumour assessments were performed at baseline (tumour assessment obtained within 4 weeks prior to beginning of treatment), week 8, and every 8 weeks thereafter.
Percentage of participants with best objective response: confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.0.
3 secondary outcomes
Percentage of Participants With Disease Control (DC)
Time frame: Tumour assessments were performed at baseline (tumour assessment obtained within 4 weeks prior to beginning of treatment), week 8, and every 8 weeks thereafter.
Progression Free Survival (PFS) Time
Time frame: Tumour assessments were performed at baseline (tumour assessment obtained within 4 weeks prior to beginning of treatment), week 8, and every 8 weeks thereafter.
Summary of Pre-dose Concentrations of Afatnib in Plasma
Time frame: Day 15, 29 and 57
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22325357De Greve J, Teugels E, Geers C, Decoster L, Galdermans D, De Mey J, Everaert H, Umelo I, In't Veld P, Schallier D. Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu. Lung Cancer. 2012 Apr;76(1):123-7. doi: 10.1016/j.lungcan.2012.01.008. Epub 2012 Feb 10.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BIBW2992 and BIBW2992 + paclitaxel in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Belgium, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Best Objective Response (time frame: Tumour assessments were performed at baseline (tumour assessment obtained within 4 weeks prior to beginning of treatment), week 8, and every 8 weeks thereafter.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00730925, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2014.