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

Boehringer Ingelheim14 sites in 2 countries50 target enrollmentNovember 2006

ConditionsBreast Neoplasms

InterventionsBIBW 2992

DrugsBIBW 2992

Overview

Phase: Phase 2
Intervention: BIBW 2992
Conditions: Breast Neoplasms
Sponsor: Boehringer Ingelheim
Enrollment: 50
Locations: 14
Primary Endpoint: Objective Response (OR)
Status: Completed
Last Updated: 12 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

November 2006

End Date

May 2009

Last Updated

12 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

Boehringer Ingelheim

Responsible Party

Sponsor

Eligibility 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 -
•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

Arms & Interventions

BIBW 2992

high dose once daily

Intervention: BIBW 2992

Outcomes

Primary Outcomes

Objective Response (OR)

Time Frame: 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)

Time Frame: 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 Outcomes

Overall Survival (OS)(From randomisation to end of follow-up.)
Best Change From Baseline in ECOG Performance Status(baseline till end of treatment)
Clinical Benefit (CB)(Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
Significant Change in Cardiac Left Ventricular Ejection Fraction (LVEF)(Baseline and last assessment)
Time to OR(Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
Duration of OR(Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
Progression-free Survival (PFS)(Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 29 (Cpre,ss,29)(day 29)