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

July 1, 2015 updated by: Boehringer Ingelheim

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Brighton, United Kingdom
        • 1200.68.44001 Boehringer Ingelheim Investigational Site
      • Cambridge, United Kingdom
        • 1200.68.44003 Boehringer Ingelheim Investigational Site
      • Guildford, United Kingdom
        • 1200.68.44005 Boehringer Ingelheim Investigational Site
      • Newcastle upon Tyne, United Kingdom
        • 1200.68.44004 Boehringer Ingelheim Investigational Site
      • Truro, United Kingdom
        • 1200.68.44002 Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BIBW 2992 + Trastuzumab
Find maximum tolerated dose of the non-marketed substance:BIBW 2992 given orally with fixed weekly infusion doses of 2mg/kg Herceptin. Escalating doses of BIBW 2992 starting at 20mg daily.
Drug: Trastuzumab
Load: 4mg/kg-maintain:2mg/kg/week
Drug: BIBW 2992
Increased dose cohorts from low dose to MTD

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Dose Limiting Toxicities (DLT)
Time Frame: 28 days
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
Maximum Tolerated Dose (MTD) of Afatinib in Combination With Herceptin(R)
Time Frame: 28 days
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Objective Response (OR)
Time Frame: Tumor assessment was performed at screening and every 2nd cycle until earliest time of progression, death or end of treatment.
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.
Number of Patients With Best Overall Response
Time Frame: Tumor assessment was performed at screening and every 2nd cycle until earliest time of progression, death or end of treatment.
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.
Progression Free Survival (PFS)
Time Frame: Baseline until disease progression, death or data cut-off.
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.
Summary of Concentration of Afatinib in Plasma
Time Frame: 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing
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
Time From Dosing to the Maximum Concentration of Afatinib in Plasma at Steady State (Tmax,ss)
Time Frame: 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing
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
Summary of Concentration of Herceptin in Plasma
Time Frame: 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2009

Primary Completion (Actual)

October 1, 2013

Study Completion (Actual)

October 1, 2013

Study Registration Dates

First Submitted

July 31, 2009

First Submitted That Met QC Criteria

July 31, 2009

First Posted (Estimate)

August 3, 2009

Study Record Updates

Last Update Posted (Estimate)

July 24, 2015

Last Update Submitted That Met QC Criteria

July 1, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1200.68
  • 2009-010003-89 (EudraCT Number: EudraCT)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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