BIBW 2992 and Letrozole in Hormonoresistant Metastatic Breast Cancer

Study Overview
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Brief Summary
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Progression-free rate after 16 weeks of BIBW 2992 administration in association with letrozole

Official Title
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A Phase II Study of BIBW 2992 Administration in Patients With Hormone Refractory Metastatic Breast Cancer

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: BIBW 2992
* Drug: BIBW 2992
* Drug: Letrozole
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Female patients with histologically proven breast adenocarcinoma Presence of metastatic disease No more than 2 prior chemotherapy regimens for metastatic disease, which could include trastuzumab Patients must currently be on letrozole and developed acquired resistance as defined by disease progression on letrozole following previous response (partial response or better, stable disease superior or equal to 24 weeks) Diagnosis of disease progression inferior or equal to 6 weeks prior to trial entrydefined as: Increase in the number of bone lesions on bone scan or on MRI AND/OR Increased pain in an area of known bony metastasis AND superior or equal to 2 serial elevations in CA 15.3 AND/OR Progression according to RECIST criteria on CT scan, MRI, or x-ray Patients must have documented menopause confirmed by estradiol level inferior to 11 pg/ml Exclusion criteria: Premenopausal patients Rapidly progressive disease in major organs (i.e. lymphangitic spread in the lung and/or bulky liver metastasis) Patient with brain metastasis Significant cardiovascular diseases Previous treatment with an EGFR and/or HER-2 inhibiting drug(patients who received trastuzumab with chemotherapy but not with letrozole can be enrolled)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBW 2992<br>To study BIBW 2992 in association with letrozole in hormonoresistant metastatic breast cancer | Drug: BIBW 2992<br>* BIBW 2992 at high and medium dosages<br>Drug: Letrozole<br>* Letrozole at standard dosage<br>|
| Other: Letrozole<br>Hormonotherapy for metastatic breast cancer | Drug: BIBW 2992<br>* BIBW 2992 at high and medium dosages<br>Drug: Letrozole<br>* Letrozole at standard dosage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Progression Free Participants After 16 Weeks of Treatment | Progression was defined according to 1 of the following criteria: New bone lesion(s) on bone scan or on magnetic resonance imaging; Progression or occurrence of new lesion(s) according to the Response Evaluation Criteria In Solid Tumours version 1.0 (RECIST); an increase in tumour marker CA 15.3 of more than 20 percent,compared with baseline, at 2 consecutive examinations; occurrence of disease-related skeletal events. If a patient did not fulfil any criteria and was withdrawn because of clinical deterioration amounting to PD according to the Investigator, they were considered as having PD. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Confirmed Objective Response (OR) | OR was defined as complete response (CR) or partial response (PR) and was assessed according to RECIST criteria regardless of treatment status. | Baseline till progression | 
| Number of Participants With Clinical Benefit (CB) | CB was defined as CR, PR or stable disease (SD) and was assessed according to RECIST criteria regardless of treatment status. | 16 weeks and 24 weeks | 
| Time to RECIST Tumour Reponse | 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 criteria. | Baseline till progression | 
| Duration of Confirmed OR | Duration of confirmed OR is measured from the time of first OR to the time of progression or death (or date of censoring for progression free survival). | First occurence or OR till progression or death | 
| 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. Progression was assessed according to RECIST criteria. | Baseline till progression, death or data cut-off (04 Jan 2010) | 
| Overall Survival (OS) | OS was defined as the time from first treatment to death. | Baseline till progression, death or data cut-off | 
| Area Under Curve of Afatinib Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss) | AUCtau,ss represents the area under the concentration curve of afatinib in plasma over a uniform dosing interval tau at steady state. | 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing | 
| Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss) | Cmax,ss represents the maximum measured concentration of afatinib in plasma at steady state. | 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing | 
| Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 57 (Cpre,ss,57) | Cpre,ss,57 represents the pre-dose concentration of afatinib in plasma at steady state on day 57. | Day 57 | 
| Pre-dose Concentration of Afatinib in Plasma at Steady Stateon Day 85 (Cpre,ss,85) | Cpre,ss,85 represents the pre-dose concentration of afatinib in plasma at steady state on day 85. | Day 85 | 
| Time From Dosing to the Maximum Concentration of Afatinib in Plasma at Steady State (Tmax,ss) | 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 2h, 4h, 6h, 8h and 24h after dosing | 
| Area Under Curve of Letrozole Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss) | AUC0-tau,ss represents the area under the concentration curve of letrozole in plasma over a uniform dosing interval tau at steady state. | 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing | 
| Maximum Concentration of Letrozole in Plasma at Steady State (Cmax,ss) | Cmax,ss represents the maximum measured concentration of letrozole in plasma at steady state. | 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing | 
| Time From Dosing to the Maximum Concentration of Letrozole in Plasma at Steady State (Tmax,ss) | tmax,ss represents the time from dosing to the maximum concentration of letrozole in plasma at steady state. | 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing | 
| Change From Baseline in Ca15.3 | Change from baseline in Ca15.3 tumor marker levels | baseline and day 29 | 
| 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). Improvement is a decrease in ECOG score from baseline of at least 1. Deterioration is an increase in ECOG score from baseline of at least 1 | baseline till end of treatment |