An Open Label Phase II Trial of BIBW 2992 in Patients With HER2-negative Metastatic Breast Cancer
- Registration Number
- NCT00425854
- Lead Sponsor
- Boehringer Ingelheim
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 50
- 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:
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BIBW 2992 BIBW 2992 high dose once daily
- Primary Outcome Measures
Name Time Method Objective Response (OR) Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. 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.
Clinical Benefit (CB) Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. 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.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) From randomisation to end of follow-up. OS is defined as time from randomisation to death.
Best Change From Baseline in ECOG Performance Status baseline till end of treatment Best change from baseline in ECOG (Eastern Cooperative Oncology Group) performance status. ECOG is measured as score between 0 (fully active) and 5 (dead).
Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 29 (Cpre,ss,29) day 29 Cpre,ss,29 represents the pre-dose concentration of afatinib in plasma at steady state on day 29.
Progression-free Survival (PFS) Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. 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.
Significant Change in Cardiac Left Ventricular Ejection Fraction (LVEF) Baseline and last assessment 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.
Duration of OR Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. 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.
Clinical Benefit (CB) Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. 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 to OR Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. 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.
Trial Locations
- Locations (14)
1200.10.49006 Boehringer Ingelheim Investigational Site
🇩🇪Wiesbaden, Germany
1200.10.3204 Boehringer Ingelheim Investigational Site
🇧🇪Leuven, Belgium
1200.10.49003 Boehringer Ingelheim Investigational Site
🇩🇪Kiel, Germany
1200.10.49004 Boehringer Ingelheim Investigational Site
🇩🇪Mainz, Germany
1200.10.3201 Boehringer Ingelheim Investigational Site
🇧🇪Bruxelles, Belgium
1200.10.3203 Boehringer Ingelheim Investigational Site
🇧🇪Charleroi, Belgium
1200.10.49007 Boehringer Ingelheim Investigational Site
🇩🇪Düsseldorf, Germany
1200.10.49010 Boehringer Ingelheim Investigational Site
🇩🇪Essen, Germany
1200.10.49005 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1200.10.49008 Boehringer Ingelheim Investigational Site
🇩🇪Erlangen, Germany
1200.10.3208 Boehringer Ingelheim Investigational Site
🇧🇪Brussel, Belgium
1200.10.3205 Boehringer Ingelheim Investigational Site
🇧🇪Gent, Belgium
1200.10.3206 Boehringer Ingelheim Investigational Site
🇧🇪Wilrijk, Belgium
1200.10.49001 Boehringer Ingelheim Investigational Site
🇩🇪München, Germany