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

Breast Neoplasms Clinical Trial

Official title:

Randomised Phase II Study of Neoadjuvant BIBW 2992 Versus Herceptin Versus Lapatinib in Her2 Positive Breast Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00826267
• Other study ID #: 1200.44
• Status: Completed
• Phase: Phase 2
• First received: January 20, 2009
• Last updated: December 5, 2013
• Start date: January 2009

Study information

• Verified date: August 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Health Surveillance AgencyColombia: Instituto Nacional de Vigilancia de Medicamentos y AlimentosPeru: General Directorate of Pharmaceuticals, Devices, and DrugsUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• lapatinib
lapatinib tablets 1500 mg daily
• BIBW 2992
BIBW 2992 high dose once daily (allowed dose reduction to medium or low once daily in case of AE)
• trastuzumab
trastuzumab 4mg/kg i.v. week 1, followed by 2mg/kg i.v. weekly

Locations

Country	Name	City	State
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
Colombia	1200.44.14002 Boehringer Ingelheim Investigational Site	Bogotá
Colombia	1200.44.14001 Boehringer Ingelheim Investigational Site	Cali
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
United States	1200.44.01001 Boehringer Ingelheim Investigational Site	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Brazil,  Colombia,  Peru, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response (OR)	Objective response (complete or partial) was assessed according to RECIST 1.0 criteria.	Tumour assessments were performed at screening, day 22 and day 43.	No
Secondary	Number of Participants Who Achieved Clinical Benefit (CB)	CB was defined as CR, PR or stable disease (SD) and was assessed according to RECIST criteria regardless of treatment status.	Tumour assessments were performed at screening, day 22 and day 43.	No
Secondary	Change From Baseline in the Diameter of the Primary Target Lesion.	Change was based on the primary lesion only rather that the sum of the target lesions as most patients had only one lesion.	3 weeks or 6 weeks	No
Secondary	Plasma Concentration of Afatinib	Individual drug plasma concentrations of afatinib after multiple oral administrations at day 7	Day 7	No
Secondary	Changes in Biomarker in Tumour Biopsies	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.	Screening, day 22, day 43	No

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