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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00950742
First received: July 31, 2009
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Breast Neoplasms
Drug: Trastuzumab
Drug: BIBW 2992
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Number of Participants With Dose Limiting Toxicities (DLT) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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.

  • Maximum Tolerated Dose (MTD) of Afatinib in Combination With Herceptin(R) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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).

  • 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. ] [ Designated as safety issue: No ]
    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.

  • Progression Free Survival (PFS) [ Time Frame: Baseline until disease progression, death or data cut-off. ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    tmax,ss represents the time from dosing to the maximum concentration of afatinib in plasma at steady state

  • 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 ] [ Designated as safety issue: No ]
    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).


Enrollment: 18
Study Start Date: August 2009
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

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

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.

  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: NCT00950742

Locations
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, United Kingdom
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00950742     History of Changes
Other Study ID Numbers: 1200.68, 2009-010003-89
Study First Received: July 31, 2009
Results First Received: August 8, 2013
Last Updated: January 24, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014