6 Weeks Treatment of Locally Advanced Breast Cancer With BIBW 2992 (Afatinib) or Lapatinib or Trastuzumab

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00826267
First received: January 20, 2009
Last updated: December 5, 2013
Last verified: August 2013
  Purpose

An open-label, randomized three-arm Phase II trial to explore the efficacy of BIBW 2992 as a single agent versus lapatinib versus trastuzumab in patients with HER2-positive treatment-naïve Stage IIIa locally advanced breast cancer. Additional information will be obtained on the safety profile and pharmacokinetics of BIBW 2992.


Condition Intervention Phase
Breast Neoplasms
Drug: lapatinib
Drug: BIBW 2992
Drug: trastuzumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomised Phase II Study of Neoadjuvant BIBW 2992 Versus Herceptin Versus Lapatinib in Her2 Positive Breast Cancer Patients

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, day 22 and day 43. ] [ Designated as safety issue: No ]
    Objective response (complete or partial) was assessed according to RECIST 1.0 criteria.


Secondary Outcome Measures:
  • Number of Participants Who Achieved Clinical Benefit (CB) [ Time Frame: Tumour assessments were performed at screening, day 22 and day 43. ] [ Designated as safety issue: No ]
    CB was defined as CR, PR or stable disease (SD) and was assessed according to RECIST criteria regardless of treatment status.

  • Change From Baseline in the Diameter of the Primary Target Lesion. [ Time Frame: 3 weeks or 6 weeks ] [ Designated as safety issue: No ]
    Change was based on the primary lesion only rather that the sum of the target lesions as most patients had only one lesion.

  • Plasma Concentration of Afatinib [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
    Individual drug plasma concentrations of afatinib after multiple oral administrations at day 7

  • Changes in Biomarker in Tumour Biopsies [ Time Frame: Screening, day 22, day 43 ] [ Designated as safety issue: No ]
    Changes in the biomarkers (Phospho-MAP-Kinase (MAPK), Total MAPK expression, EGFR, HER2, Phospho-EGFR and -HER2, Proliferation marker (Ki67 and p27), Apoptotic index (cleaved caspase 3), Phosphate and tensin homolog (PTEN), HER2 homodimerisation by HERmark assay and Phospho AKT) from biopsy tissue.


Enrollment: 29
Study Start Date: January 2009
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBW 2992
BIBW 2992 high dose once daily (allowed dose reduction to medium or low once daily in case of AE)
Drug: BIBW 2992
BIBW 2992 high dose once daily (allowed dose reduction to medium or low once daily in case of AE)
Active Comparator: Lapatinib
Lapatinib tablets 1500 mg daily.
Drug: lapatinib
lapatinib tablets 1500 mg daily
Active Comparator: Trastuzumab
Trastuzumab 4mg/kg i.v. week 1, followed by 2mg/kg i.v. weekly.
Drug: trastuzumab
trastuzumab 4mg/kg i.v. week 1, followed by 2mg/kg i.v. weekly

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Female, age 18 years or older.
  2. Histologically proven breast cancer who have not received any prior therapy.
  3. Locally advanced disease Stage IIIa with no evidence of distant metastatic disease other than anatomical site lymph nodes.
  4. HER2-positive.

Exclusion criteria:

  1. Absolute neutrophil count (ANC) less than 1500/mm3.
  2. Platelet count less than 100 000/ mm3.
  3. Hemoglobin level less than 9.0 g/dl.
  4. Bilirubin greater than 1.5 mg/dI.
  5. Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than twice the upper limit of normal.
  6. Serum creatinine greater than 1.5 times of the upper normal limit.
  7. Significant or recent acute gastrointestinal disorders with diarrhea
  8. Pregnancy or breast-feeding.
  9. Organ system dysfunction including cardiac (LVEF < 50%).
  10. Prior chemotherapy, radiotherapy or hormone therapy. Previous treatment with trastuzumab, EGFR, or EGFR/HER2-inhibitors.
  11. Other malignancies diagnosed within the past five years.
  12. Serious active infection. HIV, active hepatitis B or C.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00826267

Locations
United States, Texas
1200.44.01001 Boehringer Ingelheim Investigational Site
Houston, Texas, United States
Brazil
1200.44.12008 Boehringer Ingelheim Investigational Site
Brasilia, Brazil
1200.44.12011 Boehringer Ingelheim Investigational Site
Cachoeiro de Itapemirim, Brazil
1200.44.12012 Boehringer Ingelheim Investigational Site
Campo Grande, Brazil
1200.44.12009 Boehringer Ingelheim Investigational Site
Caxias do Sul, Brazil
1200.44.12010 Boehringer Ingelheim Investigational Site
Goiania, Brazil
1200.44.12005 Boehringer Ingelheim Investigational Site
Ijui, Brazil
1200.44.12007 Boehringer Ingelheim Investigational Site
Natal, Brazil
1200.44.12004 Boehringer Ingelheim Investigational Site
Novo Hamburgo, Brazil
1200.44.12001 Boehringer Ingelheim Investigational Site
Porto Alegre, Brazil
1200.44.12013 Boehringer Ingelheim Investigational Site
Porto Alegre, Brazil
Colombia
1200.44.14002 Boehringer Ingelheim Investigational Site
Bogotá, Colombia
1200.44.14001 Boehringer Ingelheim Investigational Site
Cali, Colombia
Peru
1200.44.19005 Boehringer Ingelheim Investigational Site
Cercado, Peru
1200.44.19001 Boehringer Ingelheim Investigational Site
Lima, Peru
1200.44.19004 Boehringer Ingelheim Investigational Site
Lima, Peru
1200.44.19003 Boehringer Ingelheim Investigational Site
San Isidro, Peru
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: NCT00826267     History of Changes
Other Study ID Numbers: 1200.44
Study First Received: January 20, 2009
Results First Received: August 8, 2013
Last Updated: December 5, 2013
Health Authority: Brazil: National Health Surveillance Agency
Colombia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Trastuzumab
Lapatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014