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BIBW 2992 (Afatinib) and Vinorelbine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01531764
Recruitment Status : Terminated (The recruitment was discontinued because of failure to meet expected enrolment goals)
First Posted : February 13, 2012
Last Update Posted : October 18, 2013
Boehringer Ingelheim
Information provided by:
University of Magdeburg

Brief Summary:

This open-label, single-arm, multicentre phase II trial will be performed in patients with intermediate HER2-positive, metastatic breast cancer (MBC)pretreated with anthracyclines and one first-line therapy in the metastatic setting.

The main objective of the trial is to evaluate the efficacy and safety of BIBW 2992 in combination with vinorelbine in patients with intermediate HER2-positive MBC. If this trial shows promising results, further studies to evaluate the benefit of BIBW 2992 in combination with chemotherapy in this subgroup of intermediate HER2-positive patients with MBC are warranted.

Patients will be followed until progression. After progression, for the purpose of analysing overall survival, information on vital status and subsequent treatment will be collected.

The primary objective is to determine the 6-month progression free survival rate of BIBW 2992 and vinorelbine i.v. in patients with metastatic, HER2 IHC 2+, HER2 FISH-negative breast cancer.

BIBW 2992 in combination with vinorelbine will provide a suitable combination to test the hypothesis that patients with metastatic breast cancer whose tumours are HER2 2+ by immunohistochemistry, but negative by fluorescence in-situ hybridisation (FISH) will benefit from a combination of a cytotoxic agent, i.e. vinorelbine, plus the dual irreversible EGFR/HER2-tyrosine kinase inhibitor BIBW 2992.

Condition or disease Intervention/treatment Phase
Carcinoma Breast Stage IV Drug: BIBW 2992 in combination with vinorelbine Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single-arm, Open-label, Multicentre Phase II Study Evaluating the Efficacy and Safety of BIBW 2992 (Afatinib) in Combination With Vinorelbine for the Treatment of Patients With Metastatic Breast Cancer With Intermediate HER2 Expression (HER2 2+ by Immunohistochemistry, Fluorescence In-situ Hybridisation (FISH) Negative) After Failure of First-line Therapy in the Metastatic Setting and Having Been Pre-treated With Anthracyclines
Study Start Date : July 2012
Actual Primary Completion Date : September 2013
Actual Study Completion Date : September 2013

Resource links provided by the National Library of Medicine

Intervention Details:
  • Drug: BIBW 2992 in combination with vinorelbine
    Patients will receive BIBW 2992 and vinorelbine chemotherapy. BIBW 2992: 40 mg oral (tablet) once daily Vinorelbine: 25 mg/m² on days 1 & 8 in a 3-weekly course, intravenous, short infusion of about 10 minutes
    Other Name: Afatinib

Primary Outcome Measures :
  1. Progression-free survival based on tumor imaging according to RECIST 1.1 criteria. [ Time Frame: 6 months defined as the time from the date of treatment start ]
    The primary objective is to determine the 6-month Progression free survival rate of BIBW 2992 and vinorelbine i.v. in patients with metastatic, HER2 IHC 2+, HER2 FISH-negative breast cancer. The analysis will be based upon the evaluation of tumour imaging. Disease progression will be evaluated according to the RECIST 1.1 criteria.

Secondary Outcome Measures :
  1. Overall survival including assessment of objective response rate and time to progression. [ Time Frame: From start of treatment until the date of first documented progression or death from any cause, whichever came first, assessed approximately up to 24 months. ]
    Objective Response Rate based on Response Evaluation Criteria in Solid Tumours (RECIST 1.1), Time-to-Progression and Overall Survival.

  2. Number, intensity and incidence of adverse events [ Time Frame: Start of treatment up to 28 days after the last administration trial medication. ]
    Safety will be evaluated as indicated by number, intensity and incidence of adverse events, graded according to US NCI CTCAE Version 4.0.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Female patients ≥ 18 years
  • Histologically confirmed diagnosis of intermediate HER2-overexpressing breast cancer
  • Stage IV metastatic disease
  • Must have received anthracycline-based chemotherapy for adjuvant treatment of breast cancer or first-line treatment of metastatic breast cancer
  • Must have received one first-line chemotherapy for metastatic breast cancer
  • Must have (archived) tumour tissue sample available for central re- assessment of HER2 status and prove to be intermediate HER2-positive. HER2 intermediate status is defined as IHC 2+ and FISH-negativity.
  • Must have at least one measurable lesion according to RECIST 1.1. Patient with only skin lesions will not be eligible.
  • Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
  • Life expectancy of at least six (6) months.
  • Written informed consent that is consistent with ICH-GCP guidelines.
  • Must be eligible for treatment with BIBW 2992 and vinorelbine.

Exclusion Criteria:

  • 1. Prior treatment with EGFR/HER2-targeted tyrosine kinase inhibitors, i.e. lapatinib
  • Prior treatment with vinorelbine
  • Known pre-existing interstitial lung disease
  • Radiotherapy, chemotherapy, hormone therapy, immunotherapy or surgery (other than biopsy) within 4 weeks (2 weeks for hormone therapy) prior to start of treatment with BIBW 2992 and vinorelbine.
  • Active brain metastases
  • Any other current malignancy or malignancy diagnosed within the past five (5) years (other than non-melanomatous skin cancer and in situ cervical cancer).
  • Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom, e.g. Crohn's disease, malabsorption or CTC grade ≥ 2 diarrhoea of any aetiology.
  • History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of ≥3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to start of study treatment.
  • Cardiac left ventricular function with resting ejection fraction of less than 50 %.
  • Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
  • Laboratory values according to specified ranges.
  • Women of childbearing potential, unwilling to use a medically acceptable method of contraception during the trial.
  • Pregnancy or breast-feeding.
  • Patients unable to comply with the protocol.
  • Known hepatitis B infection, known hepatitis C infection or known HIV carrier.
  • Known or suspected active drug or alcohol abuse.
  • Requirement for treatment with any of the prohibited concomitant medications
  • Any contraindications for therapy with vinorelbine or BIBW 2992.
  • Known hypersensitivity to BIBW 2992 or the excipients of any of the trial drugs.
  • Use of any investigational drug within 4 weeks of start of treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01531764

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Klinikum St. Marien Amberg
Amberg, Bayern, Germany, 92224
Hämato-Onkologische Schwerpunktpraxis
München, Bayern, Germany, 80638
Caritas-Krankenhaus, Onkologisches Zentrum Regensburg
Regenburg, Bayern, Germany, 93053
Gynäkologische Praxis
Hildesheim, Niedersachsen, Germany, 31134
Schwerpunktpraxis für Hämatologie und Onkologie
Bottrop, Nordrhein-Westfalen, Germany, 46236
Universitätsklinikum Frauenklinik Düsseldorf
Düsseldorf, Nordrhein-Westfalen, Germany, 40225
Otto-von-Guericke-Universität Frauenklinik Magdeburg
Magdeburg, Sachsen-Anhalt, Germany, 39108
Klinikum Chemnitz gGmbH
Chemnitz, Sachsen, Germany, 09116
Praxisklinik Krebsheilkunde für Frauen / Brustzentrum
Berlin, Germany, 10367
Onkologisches Zentrum Süd, Vivantes Tumorzentrum
Berlin, Germany, 12351
Internistische Praxisgemeinschaft Eppendorf
Hamburg, Germany, 20249
OncoResearch Lerchenfled UG
Hamburg, Germany, 22081
Sponsors and Collaborators
University of Magdeburg
Boehringer Ingelheim
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Principal Investigator: Joachim Bischoff, MD Otto-von-Guericke-Universität Magdeburg, Germany
Layout table for additonal information Identifier: NCT01531764    
Other Study ID Numbers: 1200.137
First Posted: February 13, 2012    Key Record Dates
Last Update Posted: October 18, 2013
Last Verified: February 2012
Keywords provided by University of Magdeburg:
Metastatic breast cancer
intermediate HER2 expression
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors