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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: BIBW 2992

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIBW 2992; high dose once daily	Drug: BIBW 2992; high dose once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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).	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.	day 29

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: January 22, 2007
• First Submitted That Met QC Criteria: January 22, 2007
• First Posted (Estimate): January 23, 2007

Study Record Updates

• Last Update Posted (Estimate): December 31, 2013
• Last Update Submitted That Met QC Criteria: December 5, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Afatinib
• Other Study ID Numbers: 1200.10; 2006-002018-36 (EudraCT Number: EudraCT)