BIBW 2992 and Letrozole in Hormonoresistant Metastatic Breast Cancer

Phase 2CompletedNCT00708214

Boehringer Ingelheim28 enrolled

Overview

Progression-free rate after 16 weeks of BIBW 2992 administration in association with letrozole

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Breast Neoplasms

Interventions

BIBW 2992DRUG

BIBW 2992 at high and medium dosages

BIBW 2992DRUG

BIBW 2992 at high and medium dosages

LetrozoleDRUG

Letrozole at standard dosage

Letrozole

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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: 1. Increase in the number of bone lesions on bone scan or on MRI AND/OR 2. Increased pain in an area of known bony metastasis AND superior or equal to 2 serial elevations in CA 15.3 AND/OR 3. 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)

Locations (5)

1200.5.3306A Boehringer Ingelheim Investigational Site

Caen, France

1200.5.3304A Boehringer Ingelheim Investigational Site

Nice, France

1200.5.3301A Boehringer Ingelheim Investigational Site

Paris, France

1200.5.3305A Boehringer Ingelheim Investigational Site

Paris, France

Outcomes

Primary Outcomes

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.

Time frame: 16 weeks

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: First occurence or OR till progression or death

Progression-free Survival (PFS)

Data from ClinicalTrials.gov

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Letrozole at standard dosage

1200.5.3302A Boehringer Ingelheim Investigational Site

Saint-Cloud, France

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: baseline till end of treatment