Phase I Open Label Trial to Assess Safety of BIBW 2992 (Afatinib) in Combination With Herceptin® in Patients With HER2-positive Advanced Breast Cancer.

Breast Neoplasms Clinical Trial

Official title:

Phase I Open Label Trial to Assess Safety of BIBW 2992 in Combination With Herceptin® in Patients With HER2-positive Advanced Breast Cancer.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00950742
• Other study ID #: 1200.68
• Secondary ID: 2009-010003-89
• Status: Completed
• Phase: Phase 1
• First received: July 31, 2009
• Last updated: July 1, 2015
• Start date: August 2009
• Est. completion date: October 2013

Study information

• Verified date: July 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

Study to determine the Maximum Tolerated dose of BIBW 2992 given in combination with Herceptin®

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Female patients aged >18 years.

2. Advanced or metastatic breast cancer that over-expresses HER2 (immunohistochemistry 3+ or 2+ and gene amplification by FISH). Prior treatment with Herceptin® or Lapatinib® (in the adjuvant or metastatic settings) is permitted but not required.

Exclusion criteria:

Patients with untreated or symptomatic brain metastases. Prior treatment with EGFR targeting therapies or treatment with EGFR- or HER2 inhibiting drugs within the past four weeks before the start of therapy or concomitantly with this study.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Trastuzumab
Load: 4mg/kg-maintain:2mg/kg/week
• BIBW 2992
Increased dose cohorts from low dose to MTD

Locations

Country	Name	City	State
United Kingdom	1200.68.44001 Boehringer Ingelheim Investigational Site	Brighton
United Kingdom	1200.68.44003 Boehringer Ingelheim Investigational Site	Cambridge
United Kingdom	1200.68.44005 Boehringer Ingelheim Investigational Site	Guildford
United Kingdom	1200.68.44004 Boehringer Ingelheim Investigational Site	Newcastle upon Tyne
United Kingdom	1200.68.44002 Boehringer Ingelheim Investigational Site	Truro

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose Limiting Toxicities (DLT)	Number of participants with DLT in the first cycle (28 days) for the determination of the maximum tolerated dose (MTD). Important Limitations and Caveats are provided in the respective section.	28 days	No
Primary	Maximum Tolerated Dose (MTD) of Afatinib in Combination With Herceptin(R)	The MTD was defined as the highest dose at which no more than 1 of 6 patients experienced DLT. It was determined using a standard 3 + 3 dose escalation cohort design. To confirm the MTD, the MTD cohort was to be expanded to 18 patients with no more than 3/18 patients experiencing a DLT. Please refer to CAVEATs and Limitations.	28 days	No
Secondary	Number of Patients With Objective Response (OR)	Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.1. OR is defined as complete response (CR) or partial response (PR).	Tumor assessment was performed at screening and every 2nd cycle until earliest time of progression, death or end of treatment.	No
Secondary	Number of Patients With Best Overall Response	Best overall response based on response evaluation criteria in solid tumors (RECIST) version 1.1. Best overall response is defined as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) or not evaluable.	Tumor assessment was performed at screening and every 2nd cycle until earliest time of progression, death or end of treatment.	No
Secondary	Progression Free Survival (PFS)	PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by central independent review according to the response evaluation criteria in solid tumors (RECIST 1.1). Median time results from unstratified Kaplan-Meier estimates.	Baseline until disease progression, death or data cut-off.	No
Secondary	Summary of Concentration of Afatinib in Plasma	Pre-dose Concentrations of Afatinib in Plasma at Steady State on Days 8, 15 and 29 (Cpre,ss,8, Cpre,ss,15 and Cpre,ss,29) and Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss).	0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing	No
Secondary	Time From Dosing to the Maximum Concentration of Afatinib in Plasma at Steady State (Tmax,ss)	tmax,ss represents the time from dosing to the maximum concentration of afatinib in plasma at steady state	0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing	No
Secondary	Summary of Concentration of Herceptin in Plasma	Pre-dose Concentrations of Herceptin in Plasma on Days 8, 15 and 29 (Cpre,8, Cpre,15 and Cpre,29) and Maximum Concentration of Herceptin in Plasma on Days 1, 15 and 29 (Cmax,1, Cmax,15 and Cmax,29).	0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing	No

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