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An Open Label Phase II Trial of BIBW 2992 in Patients With HER2-negative Metastatic Breast Cancer

Primary Purpose

Breast Neoplasms

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

BIBW 2992

About this trial

This is an interventional diagnostic trial for Breast Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion criteria:

Inclusion Criteria:

Female patients age 18 years or older
Histologically proven breast cancer after failure or relapse of no more than three lines of chemotherapy including adjuvant, irrespective of prior hormone therapy metastatic disease (stage IV);
HER2-negative patients (HER2 1+ or negative, or HER2 2+ and FISH negative)
At least one measurable tumour lesion (RECIST);
Availability of tumour samples
Written informed consent that is consistent with ICH-GCP guidelines and local law
Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0 - 2.

Exclusion criteria:

Exclusion Criteria:

Active infectious disease
Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhoea
Serious illness, concomitant non-oncological disease or mental problems considered by the investigator to be incompatible with the protocol
Active/symptomatic brain metastases
Cardiac left ventricular function with resting ejection fraction < 50% (below upper limit of normal)
ANC less than 1500/mm3 platelet count less than 100 000/mm3
Bilirubin greater than 1.5 mg /dl (>26 and#61549 mol /L, SI unit equivalent)
AST and ALT greater than 2.5 times the upper limit of normal or greater 5 times the upper limit of normal in case of known liver metastases
Serum creatinine greater than 1.5 mg/dl (>132 and#61549 mol/L, SI unit equivalent)
Patients who are sexually active and unwilling to use a medically acceptable method of contraception
Pregnancy or breast-feeding
Concomitant treatment with other investigational drugs or other anti-cancer-therapy during this study and/or during the past two/four weeks, prior to the first treatment with the trial drug. Concurrent treatment with biphosphonates is allowed
Previous treatment with trastuzumab, EGFR-, or EGFR/HER2-inhibitors patients unable to comply with the protocol
Active alcohol or drug abuse
Other malignancy within the past 5 years

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BIBW 2992

Arm Description

high dose once daily

Outcomes

Primary Outcome Measures

Objective Response (OR)

OR is defined as complete response (CR) and partial response (PR) and was assessed according to the Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST). OR was primary endpoint only for Cohort B.

Clinical Benefit (CB)

CB was defined as CR, PR or stable disease (SD) for a minimum of 4 months (modified CB) and was assessed according to RECIST 1.0 criteria. CB was primary endpoint only for Cohort A.

Secondary Outcome Measures

Clinical Benefit (CB)

CB was defined as CR, PR or stable disease (SD) for a minimum of 4 months (modified CB) and was assessed according to RECIST 1.0 criteria. CB was secondary endpoint only for Cohort B as it was primary endpoint for Cohort A.

Time to OR

The time to OR was the duration from the first treatment to the time when the measurement criteria for CR and/or PR were met according to RECIST 1.0 criteria.

Duration of OR

Duration of OR was measured from the time the criteria for CR or PR (whichever was documented first) were first met until the first date that progressive disease or death was objectively documented.

Progression-free Survival (PFS)

PFS was defined as the time from the first treatment to the occurrence of tumour progression or death, whichever came first. It was assessed according to RECIST 1.0 criteria as well as by the investigators assessment. Median time results from unstratified Kaplan-Meier estimates.

Overall Survival (OS)

OS is defined as time from randomisation to death.

Significant Change in Cardiac Left Ventricular Ejection Fraction (LVEF)

LVEF as measured by echocardiography or Multiple Gated Acquisition (MUGA) scan. MUGA scan is an useful noninvasive tool for assessing the function of the heart. Significant change in LVEF values was defined as >=20 percent decrease from baseline or to below lower limit of normal, which was defined as 50 percent.

Best Change From Baseline in ECOG Performance Status

Best change from baseline in ECOG (Eastern Cooperative Oncology Group) performance status. ECOG is measured as score between 0 (fully active) and 5 (dead).

Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 29 (Cpre,ss,29)

Cpre,ss,29 represents the pre-dose concentration of afatinib in plasma at steady state on day 29.

Full Information

NCT ID

NCT00425854

First Posted

January 22, 2007

Last Updated

December 5, 2013

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT00425854

Brief Title

An Open Label Phase II Trial of BIBW 2992 in Patients With HER2-negative Metastatic Breast Cancer

Official Title

An Open Label Phase II Trial to Assess the Efficacy and Safety of a Once Daily Oral Dose of 50 mg BIBW 2992 in Two Cohorts of Patients With HER2-negative Metastatic Breast Cancer After Failure of no More Than Two Chemotherapy Regimen

Study Type

Interventional

2. Study Status

Record Verification Date

August 2013

Overall Recruitment Status

Completed

Study Start Date

November 2006 (undefined)

Primary Completion Date

May 2009 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. Study Description

Brief Summary

The purpose of this trial is to evaluate the efficacy, safety and pharmacokinetics of BIBW 2992, a dual, irreversible EGFR- and HER2-inhibitor, in two cohorts of patients with HER2-negative breast cancer after failure of no more than three regimen of prior chemotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Neoplasms

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BIBW 2992

Arm Type

Experimental

Arm Description

high dose once daily

Intervention Type

Drug

Intervention Name(s)

BIBW 2992

Intervention Description

high dose once daily

Primary Outcome Measure Information:

Title

Objective Response (OR)

Description

Time Frame