Clinical trial NCT00708214: BIBW 2992 and Letrozole in Hormonoresistant Metastatic Breast Cancer
Official title: A Phase II Study of BIBW 2992 Administration in Patients With Hormone Refractory Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-07-02
Enrollment: 28
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

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


Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of Progression Free Participants After 16 Weeks of Treatment
timeFrame: 16 weeks
Secondary outcomes:
measure: Number of Participants With Confirmed Objective Response (OR)
timeFrame: Baseline till progression
measure: Number of Participants With Clinical Benefit (CB)
timeFrame: 16 weeks and 24 weeks
measure: Time to RECIST Tumour Reponse
timeFrame: Baseline till progression
measure: Duration of Confirmed OR
timeFrame: First occurence or OR till progression or death
measure: Progression-free Survival (PFS)
timeFrame: Baseline till progression, death or data cut-off (04 Jan 2010)
measure: Overall Survival (OS)
timeFrame: Baseline till progression, death or data cut-off
measure: Area Under Curve of Afatinib Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss)
timeFrame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
measure: Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss)
timeFrame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
measure: Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 57 (Cpre,ss,57)
timeFrame: Day 57
measure: Pre-dose Concentration of Afatinib in Plasma at Steady Stateon Day 85 (Cpre,ss,85)
timeFrame: Day 85
measure: Time From Dosing to the Maximum Concentration of Afatinib in Plasma at Steady State (Tmax,ss)
timeFrame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
measure: Area Under Curve of Letrozole Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss)
timeFrame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
measure: Maximum Concentration of Letrozole in Plasma at Steady State (Cmax,ss)
timeFrame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
measure: Time From Dosing to the Maximum Concentration of Letrozole in Plasma at Steady State (Tmax,ss)
timeFrame: 0.05 hours (h) before dosing and 2h, 4h, 6h, 8h and 24h after dosing
measure: Change From Baseline in Ca15.3
timeFrame: baseline and day 29
measure: Best Change From Baseline in ECOG Performance Status
timeFrame: baseline till end of treatment
Other outcomes:
Locations:
city: Caen Cedex
country: France
facility: 1200.5.3306A Boehringer Ingelheim Investigational Site
city: Nice Cedex 2
country: France
facility: 1200.5.3304A Boehringer Ingelheim Investigational Site
city: Paris Cedex 10
country: France
facility: 1200.5.3301A Boehringer Ingelheim Investigational Site
city: Paris Cedex 20
country: France
facility: 1200.5.3305A Boehringer Ingelheim Investigational Site
city: Saint Cloud
country: France
facility: 1200.5.3302A Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Gunzer K, Joly F, Ferrero JM, Gligorov J, de Mont-Serrat H, Uttenreuther-Fischer M, Pelling K, Wind S, Bousquet G, Misset JL. A phase II study of afatinib, an irreversible ErbB family blocker, added to letrozole in patients with estrogen receptor-positive hormone-refractory metastatic breast cancer progressing on letrozole. Springerplus. 2016 Jan 19;5:45. doi: 10.1186/s40064-015-1601-7. eCollection 2016.