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

Breast Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00425854
• Other study ID #: 1200.10
• Secondary ID: 2006-002018-36
• Status: Completed
• Phase: Phase 2
• First received: January 22, 2007
• Last updated: December 5, 2013
• Start date: November 2006

Study information

• Verified date: August 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHPGermany: Bundesinstitut fuer Arzneimittel und Medizinprodukte
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• BIBW 2992
high dose once daily

Locations

Country	Name	City	State
Belgium	1200.10.3208 Boehringer Ingelheim Investigational Site	Brussel
Belgium	1200.10.3201 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	1200.10.3203 Boehringer Ingelheim Investigational Site	Charleroi
Belgium	1200.10.3205 Boehringer Ingelheim Investigational Site	Gent
Belgium	1200.10.3204 Boehringer Ingelheim Investigational Site	Leuven
Belgium	1200.10.3206 Boehringer Ingelheim Investigational Site	Wilrijk
Germany	1200.10.49005 Boehringer Ingelheim Investigational Site	Berlin
Germany	1200.10.49007 Boehringer Ingelheim Investigational Site	Düsseldorf
Germany	1200.10.49008 Boehringer Ingelheim Investigational Site	Erlangen
Germany	1200.10.49010 Boehringer Ingelheim Investigational Site	Essen
Germany	1200.10.49003 Boehringer Ingelheim Investigational Site	Kiel
Germany	1200.10.49004 Boehringer Ingelheim Investigational Site	Mainz
Germany	1200.10.49001 Boehringer Ingelheim Investigational Site	München
Germany	1200.10.49006 Boehringer Ingelheim Investigational Site	Wiesbaden

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Belgium,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.	No
Primary	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.	Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.	No
Secondary	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.	Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.	No
Secondary	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.	Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.	No
Secondary	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.	Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.	No
Secondary	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.	Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.	No
Secondary	Overall Survival (OS)	OS is defined as time from randomisation to death.	From randomisation to end of follow-up.	No
Secondary	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.	Baseline and last assessment	No
Secondary	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).	baseline till end of treatment	No
Secondary	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.	day 29	No

External Links

•   Link