CompletedNCT00425854Updated Dec 31, 2013Results posted

An Open Label Phase II Trial of BIBW 2992 in Patients With HER2-negative Metastatic Breast Cancer

A Phase 2 interventional study of BIBW 2992 in Breast Neoplasms, sponsored by Boehringer Ingelheim. Completed at 14 sites in 2 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-12-31.

Sponsored by Boehringer Ingelheim · Phase 2, Interventional, and Diagnostic

Phase: Phase 2
Study type: Interventional
Enrollment: 50
Allocation: Non-randomized
Ages: 18 Years and older
Sex: Female

Study summary

The purpose of this trial is to evaluate the efficacy, safety and pharmacokinetics of BIBW 2992, a dual, irreversible EGFR- and HER2-inhibitor, in two cohorts of patients with HER2-negative breast cancer after failure of no more than three regimen of prior chemotherapy.

Conditions studied

Breast Neoplasms

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In context

Breast Neoplasms

12,815 studies on the registry are indexed under Breast Neoplasms; 2,920 are open to participants now.

This study's enrollment of 50 is below the median of 72 across 9,494 interventional studies indexed under Breast Neoplasms.

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Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,297 studies on the registry; 56 are open to participants now.

Of its 166 completed or terminated interventional studies of FDA-regulated products, 121 (73%) have results posted.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Female
Accepts healthy volunteers: No

Eligibility criteria

Inclusion criteria:

Inclusion Criteria:

Female patients age 18 years or older
Histologically proven breast cancer after failure or relapse of no more than three lines of chemotherapy including adjuvant, irrespective of prior hormone therapy metastatic disease (stage IV);
HER2-negative patients (HER2 1+ or negative, or HER2 2+ and FISH negative)
At least one measurable tumour lesion (RECIST);
Availability of tumour samples
Written informed consent that is consistent with ICH-GCP guidelines and local law
Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0 - 2.

Exclusion criteria:

Exclusion Criteria:

Active infectious disease
Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhoea
Serious illness, concomitant non-oncological disease or mental problems considered by the investigator to be incompatible with the protocol
Active/symptomatic brain metastases
Cardiac left ventricular function with resting ejection fraction \< 50% (below upper limit of normal)
ANC less than 1500/mm3 platelet count less than 100 000/mm3
Bilirubin greater than 1.5 mg /dl (>26 and#61549 mol /L, SI unit equivalent)
AST and ALT greater than 2.5 times the upper limit of normal or greater 5 times the upper limit of normal in case of known liver metastases
Serum creatinine greater than 1.5 mg/dl (>132 and#61549 mol/L, SI unit equivalent)
Patients who are sexually active and unwilling to use a medically acceptable method of contraception
Pregnancy or breast-feeding
Concomitant treatment with other investigational drugs or other anti-cancer-therapy during this study and/or during the past two/four weeks, prior to the first treatment with the trial drug. Concurrent treatment with biphosphonates is allowed
Previous treatment with trastuzumab, EGFR-, or EGFR/HER2-inhibitors patients unable to comply with the protocol
Active alcohol or drug abuse
Other malignancy within the past 5 years

Study design

Phase: Phase 2
Primary purpose: Diagnostic
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 50 participants (actual)

Study arms

Experimental
BIBW 2992
high dose once daily
Drug: BIBW 2992

Interventions

DrugBIBW 2992
high dose once daily

What researchers measure

Primary outcomes

Objective Response (OR)
OR is defined as complete response (CR) and partial response (PR) and was assessed according to the Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST). OR was primary endpoint only for Cohort B.
Time frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Clinical Benefit (CB)
CB was defined as CR, PR or stable disease (SD) for a minimum of 4 months (modified CB) and was assessed according to RECIST 1.0 criteria. CB was primary endpoint only for Cohort A.
Time frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.

Secondary outcomes

Clinical Benefit (CB)
CB was defined as CR, PR or stable disease (SD) for a minimum of 4 months (modified CB) and was assessed according to RECIST 1.0 criteria. CB was secondary endpoint only for Cohort B as it was primary endpoint for Cohort A.
Time frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Time to OR
The time to OR was the duration from the first treatment to the time when the measurement criteria for CR and/or PR were met according to RECIST 1.0 criteria.
Time frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Duration of OR
Duration of OR was measured from the time the criteria for CR or PR (whichever was documented first) were first met until the first date that progressive disease or death was objectively documented.
Time frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Progression-free Survival (PFS)
PFS was defined as the time from the first treatment to the occurrence of tumour progression or death, whichever came first. It was assessed according to RECIST 1.0 criteria as well as by the investigators assessment. Median time results from unstratified Kaplan-Meier estimates.
Time frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Overall Survival (OS)
OS is defined as time from randomisation to death.
Time frame: From randomisation to end of follow-up.
Significant Change in Cardiac Left Ventricular Ejection Fraction (LVEF)
LVEF as measured by echocardiography or Multiple Gated Acquisition (MUGA) scan. MUGA scan is an useful noninvasive tool for assessing the function of the heart. Significant change in LVEF values was defined as \>=20 percent decrease from baseline or to below lower limit of normal, which was defined as 50 percent.
Time frame: Baseline and last assessment
Best Change From Baseline in ECOG Performance Status
Best change from baseline in ECOG (Eastern Cooperative Oncology Group) performance status. ECOG is measured as score between 0 (fully active) and 5 (dead).
Time frame: baseline till end of treatment
Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 29 (Cpre,ss,29)
Cpre,ss,29 represents the pre-dose concentration of afatinib in plasma at steady state on day 29.
Time frame: day 29

Results

Posted Oct 14, 2013

Participant flow

Participant flow — Overall Study
Milestone	Cohort A	Cohort B
Started	29	21
Completed	0	0
Not completed	29	21
Withdrew: Progressive disease	19	12
Withdrew: Dose reduction toxicity ae	8	7
Withdrew: Other adverse event	2	2

Outcome measures

SecondaryClinical Benefit (CB)

CB was defined as CR, PR or stable disease (SD) for a minimum of 4 months (modified CB) and was assessed according to RECIST 1.0 criteria. CB was secondary endpoint only for Cohort B as it was primary endpoint for Cohort A.

Time frame:: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Reported as:: Number · Participants with CB

Clinical Benefit (CB)
Participants with CB	Cohort B
With CB	1
Without CB	17
missing	3

Statistical analysis

Cohort B · Maximum likelihood: 0.048 · 95% CI 0.001 to 0.238Maximum Likelihood estimates. The clinical benefit rate for Cohort A was calculated by relating the number of patients with CB to all treated patients in Cohort B. The CI is an exact Clopper Pearson CI.

SecondaryTime to OR

The time to OR was the duration from the first treatment to the time when the measurement criteria for CR and/or PR were met according to RECIST 1.0 criteria.

Time frame:: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.

No measurements were reported for this outcome.

SecondaryDuration of OR

Duration of OR was measured from the time the criteria for CR or PR (whichever was documented first) were first met until the first date that progressive disease or death was objectively documented.

Time frame:: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.

No measurements were reported for this outcome.

SecondaryProgression-free Survival (PFS)

PFS was defined as the time from the first treatment to the occurrence of tumour progression or death, whichever came first. It was assessed according to RECIST 1.0 criteria as well as by the investigators assessment. Median time results from unstratified Kaplan-Meier estimates.

Time frame:: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Reported as:: Median · days

Progression-free Survival (PFS)
days	Cohort A	Cohort B
Progression-free Survival (PFS)	52 (39 to 71)	54 (50 to 112)

PrimaryObjective Response (OR)

OR is defined as complete response (CR) and partial response (PR) and was assessed according to the Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST). OR was primary endpoint only for Cohort B.

Time frame:: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Reported as:: Number · Participants with OR

Objective Response (OR)
Participants with OR	Cohort B
Objective Response (OR)	0

PrimaryClinical Benefit (CB)

CB was defined as CR, PR or stable disease (SD) for a minimum of 4 months (modified CB) and was assessed according to RECIST 1.0 criteria. CB was primary endpoint only for Cohort A.

Time frame:: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Reported as:: Number · Participants

Clinical Benefit (CB)
Participants	Cohort A
With CB	3
Without CB	24
missing	2

Statistical analysis

Cohort A · Maxium Likelihood · Clinical benefit rate: 0.10 · 95% CI 0.02 to 0.27Maximum Likelihood estimates. The clinical benefit rate for Cohort A was calculated by relating the number of patients with CB to all treated patients in Cohort A. The confidence interval (CI) is an exact Clopper Pearson CI.

SecondaryOverall Survival (OS)

OS is defined as time from randomisation to death.

Time frame:: From randomisation to end of follow-up.
Reported as:: Median · days

Overall Survival (OS)
days	Cohort A	Cohort B
Overall Survival (OS)	NA (120 to NA)	448 (310 to 537)

SecondarySignificant Change in Cardiac Left Ventricular Ejection Fraction (LVEF)

LVEF as measured by echocardiography or Multiple Gated Acquisition (MUGA) scan. MUGA scan is an useful noninvasive tool for assessing the function of the heart. Significant change in LVEF values was defined as \>=20 percent decrease from baseline or to below lower limit of normal, which was defined as 50 percent.

Time frame:: Baseline and last assessment
Reported as:: Number · Participants

Significant Change in Cardiac Left Ventricular Ejection Fraction (LVEF)
Participants	Cohort A	Cohort B
Significant Change in Cardiac Left Ventricular Ejection Fraction (LVEF)	1	2

SecondaryBest Change From Baseline in ECOG Performance Status

Best change from baseline in ECOG (Eastern Cooperative Oncology Group) performance status. ECOG is measured as score between 0 (fully active) and 5 (dead).

Time frame:: baseline till end of treatment
Reported as:: Number · participants

Best Change From Baseline in ECOG Performance Status
participants	Cohort A	Cohort B
improved	1	0
deteriorated	15	13

SecondaryPre-dose Concentration of Afatinib in Plasma at Steady State on Day 29 (Cpre,ss,29)

Cpre,ss,29 represents the pre-dose concentration of afatinib in plasma at steady state on day 29.

Time frame:: day 29
Reported as:: Geometric mean · ng/mL

Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 29 (Cpre,ss,29)
ng/mL	Cohort A	Cohort B
Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 29 (Cpre,ss,29)	33.1 ± 110	22.9 ± 64.7

Adverse events

Collected over First administration of trial medication until 28 days after last administration of trial medication. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cohort A	—	13/29 (44.8%)	28/29 (96.6%)
Cohort B	—	7/21 (33.3%)	20/21 (95.2%)

Most frequent serious events

Showing 10 of 30

Most frequent serious events
Event	Cohort A	Cohort B
General physical health deteriorationGeneral disorders	5/29	0/21
DiarrhoeaGastrointestinal disorders	3/29	2/21
NauseaGastrointestinal disorders	0/29	2/21
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)	2/29	2/21
VomitingGastrointestinal disorders	2/29	0/21
DehydrationMetabolism and nutrition disorders	2/29	1/21
Abdominal painGastrointestinal disorders	0/29	1/21
DysphagiaGastrointestinal disorders	0/29	1/21
Oesophageal stenosisGastrointestinal disorders	0/29	1/21
FatigueGeneral disorders	0/29	1/21

Most frequent other events

Showing 10 of 37

Most frequent other events
Event	Cohort A	Cohort B
DiarrhoeaGastrointestinal disorders	25/29	16/21
RashSkin and subcutaneous tissue disorders	9/29	10/21
NauseaGastrointestinal disorders	13/29	5/21
AcneSkin and subcutaneous tissue disorders	11/29	3/21
FatigueGeneral disorders	9/29	7/21
Mucosal inflammationGeneral disorders	9/29	6/21
VomitingGastrointestinal disorders	4/29	6/21
Decreased appetiteMetabolism and nutrition disorders	8/29	6/21
Dry skinSkin and subcutaneous tissue disorders	8/29	4/21
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders	1/29	5/21

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Cohort A	Cohort B	Total
Mean	54.3 ± 11.5	61.0 ± 14.3	57.1 ± 13.0

Sex: Female, Male
Sex: Female, Male(Participants)	Cohort A	Cohort B	Total
Female	29	21	50
Male	0	0	0

Study locations

14 sites

1200.10.3201 Boehringer Ingelheim Investigational Site
Brussels, Belgium
1200.10.3208 Boehringer Ingelheim Investigational Site
Brussels, Belgium
1200.10.3203 Boehringer Ingelheim Investigational Site
Charleroi, Belgium
1200.10.3205 Boehringer Ingelheim Investigational Site
Ghent, Belgium
1200.10.3204 Boehringer Ingelheim Investigational Site
Leuven, Belgium
1200.10.3206 Boehringer Ingelheim Investigational Site
Wilrijk, Belgium
1200.10.49005 Boehringer Ingelheim Investigational Site
Berlin, Germany
1200.10.49007 Boehringer Ingelheim Investigational Site
Düsseldorf, Germany
1200.10.49008 Boehringer Ingelheim Investigational Site
Erlangen, Germany
1200.10.49010 Boehringer Ingelheim Investigational Site
Essen, Germany
1200.10.49003 Boehringer Ingelheim Investigational Site
Kiel, Germany
1200.10.49004 Boehringer Ingelheim Investigational Site
Mainz, Germany
1200.10.49001 Boehringer Ingelheim Investigational Site
München, Germany
1200.10.49006 Boehringer Ingelheim Investigational Site
Wiesbaden, Germany

References and documents

Timeline

Tracking since Sep 25, 2026

Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Nov 2006 and a primary completion of May 2009. It does not say whether these dates are actual or estimated.

Results were first posted in Oct 2013, 4 years 5 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Jan 22, 2007
First posted: Jan 23, 2007
Start: Nov 2006
Primary completionActual: May 2009
Results first posted: Oct 14, 2013
Last update: Dec 31, 2013

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Dec 31, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00425854
Lead sponsor: Boehringer Ingelheim
Responsible party: Sponsor
First posted: Jan 23, 2007
Start date: Nov 2006
Primary completion: May 2009
Results posted: Oct 14, 2013
Last update: Dec 31, 2013

Study contacts

Boehringer Ingelheim

study chair · Boehringer Ingelheim

View the source record on ClinicalTrials.gov ↗

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