Breast NeoplasmsPhase 2NCT00826267

6 Weeks Treatment of Locally Advanced Breast Cancer With BIBW 2992 (Afatinib) or Lapatinib or Trastuzumab

A Phase 2 study testing lapatinib, BIBW 2992 and trastuzumab in people with Breast Neoplasms, run by Boehringer Ingelheim at 17 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

An open-label, randomized three-arm Phase II trial to explore the efficacy of BIBW 2992 as a single agent versus lapatinib versus trastuzumab in patients with HER2-positive treatment-naïve Stage IIIa locally advanced breast cancer. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Breast Neoplasms
What is being tested?: lapatinib, BIBW 2992 and trastuzumab
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 29 participants
Where: 17 sitesin 4 countries
Study dates: Jan 2009to Aug 2011
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
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Female, age 18 years or older.
Histologically proven breast cancer who have not received any prior therapy.
Locally advanced disease Stage IIIa with no evidence of distant metastatic disease other than anatomical site lymph nodes.
HER2-positive.

Who cannot join

Absolute neutrophil count (ANC) less than 1500/mm3.
Platelet count less than 100 000/ mm3.
Hemoglobin level less than 9.0 g/dl.
Bilirubin greater than 1.5 mg/dI.
Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than twice the upper limit of normal.
Serum creatinine greater than 1.5 times of the upper normal limit.

Show all 12Show fewer

Significant or recent acute gastrointestinal disorders with diarrhea
Pregnancy or breast-feeding.
Organ system dysfunction including cardiac (LVEF < 50%).
Prior chemotherapy, radiotherapy or hormone therapy. Previous treatment with trastuzumab, EGFR, or EGFR/HER2-inhibitors.
Other malignancies diagnosed within the past five years.
Serious active infection. HIV, active hepatitis B or C.

Trial locations and contacts

17 sites in 4 countries.

Country

City, postcode or hospital

17 sites in 4 countries

Brazil10 sites

1200.44.12008 Boehringer Ingelheim Investigational Site
Brasília
1200.44.12011 Boehringer Ingelheim Investigational Site
Cachoeiro de Itapemirim
1200.44.12012 Boehringer Ingelheim Investigational Site
Campo Grande
1200.44.12009 Boehringer Ingelheim Investigational Site
Caxias do Sul
1200.44.12010 Boehringer Ingelheim Investigational Site
Goiânia
1200.44.12005 Boehringer Ingelheim Investigational Site
Ijuí
1200.44.12007 Boehringer Ingelheim Investigational Site
Natal
1200.44.12004 Boehringer Ingelheim Investigational Site
Novo Hamburgo
1200.44.12001 Boehringer Ingelheim Investigational Site
Porto Alegre
1200.44.12013 Boehringer Ingelheim Investigational Site
Porto Alegre

Other trials in Brazil

Peru4 sites

1200.44.19005 Boehringer Ingelheim Investigational Site
Cercado
1200.44.19001 Boehringer Ingelheim Investigational Site
Lima
1200.44.19004 Boehringer Ingelheim Investigational Site
Lima
1200.44.19003 Boehringer Ingelheim Investigational Site
San Isidro

Other trials in Peru

Colombia2 sites

1200.44.14002 Boehringer Ingelheim Investigational Site
Bogotá
1200.44.14001 Boehringer Ingelheim Investigational Site
Cali

Other trials in Colombia

United States1 site

1200.44.01001 Boehringer Ingelheim Investigational Site
Houston, Texas

Other trials in United States

About this study

Official title: Randomised Phase II Study of Neoadjuvant BIBW 2992 Versus Herceptin Versus Lapatinib in Her2 Positive Breast Cancer Patients

Conditions: Breast Neoplasms
Being tested: lapatinib, BIBW 2992, trastuzumab
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

lapatinibDrug
lapatinib tablets 1500 mg daily
BIBW 2992Drug
BIBW 2992 high dose once daily (allowed dose reduction to medium or low once daily in case of AE)
trastuzumabDrug
trastuzumab 4mg/kg i.v. week 1, followed by 2mg/kg i.v. weekly

Study groups in NCT00826267
Study group	Role	What they receive
BIBW 2992	Experimental	BIBW 2992 high dose once daily (allowed dose reduction to medium or low once daily in case of AE) Receives: Drug: BIBW 2992
Lapatinib	Active comparator	Lapatinib tablets 1500 mg daily. Receives: Drug: lapatinib
Trastuzumab	Active comparator	Trastuzumab 4mg/kg i.v. week 1, followed by 2mg/kg i.v. weekly. Receives: Drug: trastuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Objective Response (OR)
Objective response (complete or partial) was assessed according to RECIST 1.0 criteria.
Measured: Tumour assessments were performed at screening, day 22 and day 43.

Secondary outcomes (4)

Number of Participants Who Achieved Clinical Benefit (CB)
CB was defined as CR, PR or stable disease (SD) and was assessed according to RECIST criteria regardless of treatment status.
Measured: Tumour assessments were performed at screening, day 22 and day 43.
Change From Baseline in the Diameter of the Primary Target Lesion.
Change was based on the primary lesion only rather that the sum of the target lesions as most patients had only one lesion.
Measured: 3 weeks or 6 weeks
Plasma Concentration of Afatinib
Individual drug plasma concentrations of afatinib after multiple oral administrations at day 7
Measured: Day 7
Changes in Biomarker in Tumour Biopsies
Changes in the biomarkers (Phospho-MAP-Kinase (MAPK), Total MAPK expression, EGFR, HER2, Phospho-EGFR and -HER2, Proliferation marker (Ki67 and p27), Apoptotic index (cleaved caspase 3), Phosphate and tensin homolog (PTEN), HER2 homodimerisation by HERmark assay and Phospho AKT) from biopsy tissue.
Measured: Screening, day 22, day 43

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2009Aug 2011

First posted22 Jan 2009 (estimated)
Study startJan 2009
Primary completionAug 2011

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.
Other trials for Breast NeoplasmsStudies 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: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00826267
Sponsor's protocol ID: 1200.44
Status last verified: Aug 2013
First submitted: 20 Jan 2009
Last updated: 31 Dec 2013
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Streamlined Geriatric and Oncological Evaluation Based On IC Technology
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A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
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Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

All Breast Neoplasms trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomised Phase II Study of Neoadjuvant BIBW 2992 Versus Herceptin Versus Lapatinib in Her2 Positive Breast Cancer Patients
ClinicalTrials.gov ID: NCT00826267
Acronym / sponsor ID: 1200.44
Conditions: Breast Neoplasms
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Jan 2009
Primary completion: Aug 2011 (actual)
First posted: 22 Jan 2009 (estimated)
Results: Posted 17 Oct 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
BIBW 2992	Experimental	Drug: BIBW 2992BIBW 2992 high dose once daily (allowed dose reduction to medium or low once daily in case of AE)
Lapatinib	Active comparator	Drug: lapatinibLapatinib tablets 1500 mg daily.
Trastuzumab	Active comparator	Drug: trastuzumabTrastuzumab 4mg/kg i.v. week 1, followed by 2mg/kg i.v. weekly.

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Female, age 18 years or older.
Histologically proven breast cancer who have not received any prior therapy.
Locally advanced disease Stage IIIa with no evidence of distant metastatic disease other than anatomical site lymph nodes.
HER2-positive.

Key exclusion criteria (12 listed)

Absolute neutrophil count (ANC) less than 1500/mm3.
Platelet count less than 100 000/ mm3.
Hemoglobin level less than 9.0 g/dl.
Bilirubin greater than 1.5 mg/dI.
Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than twice the upper limit of normal.

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
lapatiniblapatinib tablets 1500 mg daily	Drug	Lapatinib
BIBW 2992BIBW 2992 high dose once daily (allowed dose reduction to medium or low once daily in case of AE)	Drug	BIBW 2992
trastuzumabtrastuzumab 4mg/kg i.v. week 1, followed by 2mg/kg i.v. weekly	Drug	Trastuzumab

Primary outcome

Objective Response (OR)
Time frame: Tumour assessments were performed at screening, day 22 and day 43.
Objective response (complete or partial) was assessed according to RECIST 1.0 criteria.

4 secondary outcomes

Number of Participants Who Achieved Clinical Benefit (CB)
Time frame: Tumour assessments were performed at screening, day 22 and day 43.
Change From Baseline in the Diameter of the Primary Target Lesion.
Time frame: 3 weeks or 6 weeks
Plasma Concentration of Afatinib
Time frame: Day 7
Changes in Biomarker in Tumour Biopsies
Time frame: Screening, day 22, day 43

Results and safety

Results posted to the registry on 17 Oct 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Afatinib 50 mg	10	9
Lapatinib 1500 mg	8	8
Trastuzumab	11	11

Primary outcome: Objective Response (OR)

Time frame: Tumour assessments were performed at screening, day 22 and day 43.. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Afatinib 50 mg n = 10	Lapatinib 1500 mg n = 8	Trastuzumab n = 11
Value	80.0 (44.4 to 97.5)	75.0 (34.9 to 96.8)	36.4 (10.9 to 69.2)

Population analysed: Treated set (TS). TS consisted of all patients who received at least one dose of study medication.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 28 days following the end-of-treatment visit.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Afatinib 50 mg	0 of 10 (0%)	10 of 10 (100%)	Not reported
Lapatinib 1500 mg	0 of 8 (0%)	8 of 8 (100%)	Not reported
Trastuzumab	0 of 11 (0%)	8 of 11 (72.7%)	Not reported

Limitations and caveats (from the sponsor): Because of slow enrollment and a high screen-failure rate, recruitment became a challenge and the sponsor chose to terminate the trial prior to reaching the target enrollment of 120 pat. Small number of subjects lead to some shortcomings in analyses.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.

Related trials for Breast Neoplasms

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
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RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
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RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

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

17 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing lapatinib, BIBW 2992 and trastuzumab in people with Breast Neoplasms, run by Boehringer Ingelheim at 17 sites in 4 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 4 inclusion and 12 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 31 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Brazil, Peru, Colombia, United States. 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 17 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?

Objective Response (OR) (time frame: Tumour assessments were performed at screening, day 22 and day 43.). 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 NCT00826267.

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 31 Dec 2013.