Advanced ER+, HER2- postmenopausal breast cancer with low ER expression
Conditions
Interventions
Product Name: Afatinib
Product Code: BIBW2992
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Afatinib
CAS Number: 850140-73-7
Current Sponsor code: BIBW2992
Other descriptive name: AFATI
Sponsors
Translational Research In Oncology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment. 2.Postmenopausal female, 18 years of age or older. Postmenopausal status defined as: oPrior bilateral surgical oophorectomy or oAmenorrhea and age ? 60 years or oAge 1.5 x ULN then calculated (Cockcroft-Gault formula) or measured Creatinine clearance ? 60 mL/min is required. 10.Baseline resting left ventricular ejection fraction (LVEF) ? 50% measured by multigated acquisition scan (MUGA scan) or echocardiogram. 11.Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 75
Exclusion criteria
Exclusion criteria: 1.Brain metastases (even if treated and/or stable), spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. 2.Prior treatment with any type of systemic therapy for locally-recurrent disease not amenable to resection or radiation therapy with curative intent, or for metastatic disease. 3.Prior treatment with letrozole in (neo)adjuvant setting with disease-free interval ? 12 months from completion of treatment until randomization. 4.Prior treatment with any anti HER-family targeted therapy in (neo)adjuvant setting. 5.Any concurrent or previous malignancy within 5 years prior to randomization except for adequately and radically treated basal or squamous skin cancer, or carcinoma in situ of the cervix, or other non-invasive/in-situ neoplasm. A subject with previous history of invasive malignancy (other than adequately and radically treated basal or squamous skin cancer) is eligible provided that she has been disease free for more than 5 years. 6.Non-measurable disease according to RECIST 1.1 (E.A. Eisenhauer 2009), with the exception of bone-only non-measurable disease. 7.Known pre-existing interstitial lung disease. 8.Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g. Crohn's disease, malabsorption or CTCAE v4.0 grade ? 2 diarrhea of any aetiology. 9.History or presence of clinically relevant cardiovascular abnormalities, as per investigator assessment such as uncontrolled hypertension, congestive heart failure NYHA Class ? III, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to randomization. 10.Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise subject safety or interfere with the evaluation of the safety of the test drug. 11.Any contraindication to oral agents. 12.Active hepatitis B infection (defined as presence of Hep B sAg and/or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) or known HIV carrier. 13.Known or suspected active drug or alcohol abuse. 14.Known hypersensitivity to afatinib or letrozole or the excipients of any of the trial drugs. 15.Concomitant treatment with strong inhibitor of P-gp. 16.Any ongoing acute clinically significant toxic effect of prior anticancer therapy or any persisting complication of prior surgery.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of letrozole plus afatinib and of letrozole alone on progression-free survival (PFS) in the first line treatment of ER+, HER2 negative postmenopausal ABC women with low ER expression.;Secondary Objective: To assess secondary measures of efficacy for afatinib administered in combination with letrozole and for letrozole alone (Overall survival - Objective Response rate - Time to tumor progression). To assess the safety and tolerability of afatinib administered in combination with letrozole and of letrozole alone (Overall safety profile).;Primary end point(s): Progression Free Survival (PFS). It is defined as the time from randomization until date of progression (assessed by RECIST) or death due to any cause, whichever occurs first.;Timepoint(s) of evaluation of this end point: Disease assessments every 12 weeks until documentation of progressive disease. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival (OS), Objective Response rate (OR) and Time to tumor progression (TTP) Overall safety profile;Timepoint(s) of evaluation of this end point: Overall survival (OS): under treatment: every 4 weeks after treatment up to documentation of disease progression: every 12 weeks after documentation of disease progression up to the end of the study: every 6 months Objective response rate and Time to Tumor Progression: every 12 weeks Overall safety Profile: under treatment: every 4 weeks (Physical examination, vital signs, blood test), every 12 weeks (LVEF) after treatment up to documentation of disease progression: every 12 weeks (AE related to the study treatment) after documentation of disease progression up to the end of the study: every 6 months (SAE related to the study treatment) | — |
Countries
Bosnia and Herzegovina, India, Spain, United States
Contacts
Public ContactProject Management
Translational Research In Oncology
Outcome results
None listed