no synonym
Conditions
Interventions
Afatinib tablets 40mg once daily continuous in 4-week cycles until disease
progression
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Locally advanced or metastatic, pathologically proven, EGFR expressing chordoma, not amenable for local therapies , - Patients of 18 years and up , - Documented radiographic progression of disease according to RECIST 1.1 criteria in last 6 months, with interval between 2 pre-treatment scans of = 6.0 mmol/L, absolute neutrophil count >= 1.5 x 109/L, platelets >= 75 x 109/L), - An adequate renal function with GFR >= 45 ml/min calculated by Cockroft-Gault formula, - Total Bilirubin
Exclusion criteria
Exclusion criteria: - Life expectancy of less than 3 months, - No measurable lesions according to RECIST 1.1, - Known hypersensitivity to afatinib, - Major surgery less than 4 weeks prior to start of treatment , - Previous treatment with any other investigational agents within 14 days of first day of study drug dosing , - History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of >= 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to inclusion., - Known pre-existing interstitial lung disease, - Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g. Crohn*s disease, ulcerative colitis, chronic diarrhea, malabsorption) , - Known active hepatitis B infection (defined as presence of HepB sAg and/ or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier., - Systemic anti-cancer therapy within 28 days prior to the first dose of study drug , or radiotherapy to an index (or target)lesion within 21 days prior to the first dose of study drug , - Requiring treatment with any of the prohibited concomitant medications listed in Section 6.3.9 that cannot be stopped for the duration of trial participation, - Pregnant or lactating women, - Other invasive malignancies diagnosed within the last 5 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer, - Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient*s ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - PFS >= 12 months in first line treatment and >= 9 months in further line treatment - Change from baseline in EORTC QLQ-C30 questionnaire / Brief pain inventory score | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints - Time to progression during afatinib treatment (TTP2) divided by time to progression before start of this treatment TTP1 (= growth modulation index) - Toxicity determined by CTCAE v 4.03 criteria - Overall survival from start of afatinib treatment Translational research endpoints - EGFR pathway and dimerization analysis in archival tumor tissue - Genome sequence analysis of available tumor samples - Analysis of circulating biomarkers in patients pre and post treatment Pharmacokinetic endpoints - Observed afatinib plasma levels, administered afatinib doses and time between afatinib doses and sampling. Used to construct: o a population PK / PD / PG model o a limited sampling model for afatinib exposure o a time to event model o tumor imaging data in relationship to afatinib exposure and genetic data of the tumor. | — |
Countries
Netherlands
Outcome results
None listed