Clinical trial NCT00425854: An Open Label Phase II Trial of BIBW 2992 in Patients With HER2-negative Metastatic Breast Cancer
Official title: An Open Label Phase II Trial to Assess the Efficacy and Safety of a Once Daily Oral Dose of 50 mg BIBW 2992 in Two Cohorts of Patients With HER2-negative Metastatic Breast Cancer After Failure of no More Than Two Chemotherapy Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-01-23
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.


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

Primary outcomes:
measure: Objective Response (OR)
timeFrame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
measure: Clinical Benefit (CB)
timeFrame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
Secondary outcomes:
measure: Clinical Benefit (CB)
timeFrame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
measure: Time to OR
timeFrame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
measure: Duration of OR
timeFrame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
measure: Progression-free Survival (PFS)
timeFrame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
measure: Overall Survival (OS)
timeFrame: From randomisation to end of follow-up.
measure: Significant Change in Cardiac Left Ventricular Ejection Fraction (LVEF)
timeFrame: Baseline and last assessment
measure: Best Change From Baseline in ECOG Performance Status
timeFrame: baseline till end of treatment
measure: Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 29 (Cpre,ss,29)
timeFrame: day 29
Other outcomes:
Locations:
city: Brussel
country: Belgium
facility: 1200.10.3208 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 1200.10.3201 Boehringer Ingelheim Investigational Site
city: Charleroi
country: Belgium
facility: 1200.10.3203 Boehringer Ingelheim Investigational Site
city: Gent
country: Belgium
facility: 1200.10.3205 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1200.10.3204 Boehringer Ingelheim Investigational Site
city: Wilrijk
country: Belgium
facility: 1200.10.3206 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1200.10.49005 Boehringer Ingelheim Investigational Site
city: Düsseldorf
country: Germany
facility: 1200.10.49007 Boehringer Ingelheim Investigational Site
city: Erlangen
country: Germany
facility: 1200.10.49008 Boehringer Ingelheim Investigational Site
city: Essen
country: Germany
facility: 1200.10.49010 Boehringer Ingelheim Investigational Site
city: Kiel
country: Germany
facility: 1200.10.49003 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1200.10.49004 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1200.10.49001 Boehringer Ingelheim Investigational Site
city: Wiesbaden
country: Germany
facility: 1200.10.49006 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: