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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00425854
First received: January 22, 2007
Last updated: December 5, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Breast Neoplasms
Drug: BIBW 2992
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Objective Response (OR) [ Time Frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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:
  • Clinical Benefit (CB) [ Time Frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. ] [ Designated as safety issue: No ]
    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.

  • Duration of OR [ Time Frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. ] [ Designated as safety issue: No ]
    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.

  • Progression-free Survival (PFS) [ Time Frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. ] [ Designated as safety issue: No ]
    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.

  • Overall Survival (OS) [ Time Frame: From randomisation to end of follow-up. ] [ Designated as safety issue: No ]
    OS is defined as time from randomisation to death.

  • Significant Change in Cardiac Left Ventricular Ejection Fraction (LVEF) [ Time Frame: Baseline and last assessment ] [ Designated as safety issue: No ]
    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.

  • Best Change From Baseline in ECOG Performance Status [ Time Frame: baseline till end of treatment ] [ Designated as safety issue: No ]
    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) [ Time Frame: day 29 ] [ Designated as safety issue: No ]
    Cpre,ss,29 represents the pre-dose concentration of afatinib in plasma at steady state on day 29.


Enrollment: 50
Study Start Date: November 2006
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBW 2992
high dose once daily
Drug: BIBW 2992
high dose once daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00425854

Locations
Belgium
1200.10.3208 Boehringer Ingelheim Investigational Site
Brussel, Belgium
1200.10.3201 Boehringer Ingelheim Investigational Site
Bruxelles, Belgium
1200.10.3203 Boehringer Ingelheim Investigational Site
Charleroi, Belgium
1200.10.3205 Boehringer Ingelheim Investigational Site
Gent, Belgium
1200.10.3204 Boehringer Ingelheim Investigational Site
Leuven, Belgium
1200.10.3206 Boehringer Ingelheim Investigational Site
Wilrijk, Belgium
Germany
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
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00425854     History of Changes
Other Study ID Numbers: 1200.10, 2006-002018-36
Study First Received: January 22, 2007
Results First Received: August 8, 2013
Last Updated: December 5, 2013
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
Germany: Bundesinstitut fuer Arzneimittel und Medizinprodukte

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on April 17, 2014