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

• ClinicalTrials.gov Identifier: NCT00425854
• Recruitment Status: Completed
• First Posted: January 23, 2007
• Results First Posted: October 14, 2013
• Last Update Posted: December 31, 2013
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

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.

Condition or disease	Intervention/treatment	Phase
Breast Neoplasms	Drug: BIBW 2992	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• 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 Start Date: November 2006
• Actual Primary Completion Date: May 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: BIBW 2992; high dose once daily	Drug: BIBW 2992; high dose once daily

Outcome Measures

Primary Outcome Measures :

1. Objective Response (OR) [ Time Frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. ]
   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.
2. Clinical Benefit (CB) [ Time Frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. ]
   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 :

1. Clinical Benefit (CB) [ Time Frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. ]
   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.
2. Time to OR [ Time Frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. ]
   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.
3. Duration of OR [ Time Frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. ]
   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.
4. Progression-free Survival (PFS) [ Time Frame: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. ]
   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.
5. Overall Survival (OS) [ Time Frame: From randomisation to end of follow-up. ]
   OS is defined as time from randomisation to death.
6. Significant Change in Cardiac Left Ventricular Ejection Fraction (LVEF) [ Time Frame: Baseline and last assessment ]
   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.
7. Best Change From Baseline in ECOG Performance Status [ Time Frame: baseline till end of treatment ]
   Best change from baseline in ECOG (Eastern Cooperative Oncology Group) performance status. ECOG is measured as score between 0 (fully active) and 5 (dead).
8. Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 29 (Cpre,ss,29) [ Time Frame: day 29 ]
   Cpre,ss,29 represents the pre-dose concentration of afatinib in plasma at steady state on day 29.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

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, Belgium

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, Germany

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

More Information

Additional Information:

Related Info 

Related Info 

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT00425854
• Other Study ID Numbers: 1200.10; 2006-002018-36 ( EudraCT Number: EudraCT )
• First Posted: January 23, 2007
• Results First Posted: October 14, 2013
• Last Update Posted: December 31, 2013
• Last Verified: August 2013

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Afatinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action