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

• ClinicalTrials.gov Identifier: NCT00826267
• Recruitment Status: Completed
• First Posted: January 22, 2009
• Results First Posted: October 17, 2013
• Last Update Posted: December 31, 2013
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: January 20, 2009
• First Posted Date: January 22, 2009
• Results First Submitted Date: August 8, 2013
• Results First Posted Date: October 17, 2013
• Last Update Posted Date: December 31, 2013
• Study Start Date: January 2009
• Actual Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 8, 2013)

Objective Response (OR) [ Time Frame: Tumour assessments were performed at screening, day 22 and day 43. ]

Objective response (complete or partial) was assessed according to RECIST 1.0 criteria.

• Original Primary Outcome Measures (submitted: January 21, 2009): Objective response rate [ Time Frame: 6 weeks ]

Current Secondary Outcome Measures (submitted: August 8, 2013)

• Number of Participants Who Achieved Clinical Benefit (CB) [ Time Frame: Tumour assessments were performed at screening, day 22 and day 43. ]
  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 ]
  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 ]
  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 ]
  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.

• Original Secondary Outcome Measures (submitted: January 21, 2009): Clinical benefit rate, PK, changes in biomarker in tumor biopsies, safety
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 6 Weeks Treatment of Locally Advanced Breast Cancer With BIBW 2992 (Afatinib) or Lapatinib or Trastuzumab
• Official Title: Randomised Phase II Study of Neoadjuvant BIBW 2992 Versus Herceptin Versus Lapatinib in Her2 Positive Breast Cancer Patients
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Neoplasms

Intervention

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

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 21, 2011): 29
• Original Estimated Enrollment (submitted: January 21, 2009): 120
• Study Completion Date: Not Provided
• Actual Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, Colombia, Peru, United States
• Removed Location Countries: Argentina, Chile, Costa Rica, Mexico, Panama

Administrative Information

• NCT Number: NCT00826267
• Other Study ID Numbers: 1200.44
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Boehringer Ingelheim
• Study Sponsor: Boehringer Ingelheim
• Collaborators: Not Provided

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

• PRS Account: Boehringer Ingelheim
• Verification Date: August 2013