Afatinib in Locally Advanced and Metastatic Chordoma

Inclusion Criteria:

• Locally advanced or metastatic, pathologically proven, EGFR expressing chordoma, notamenable for local therapies

• Patients of 18 years and up

• Documented radiographic progression of disease according to RECIST 1.1 criteria inlast 6 months

• ECOG Performance status ≤ 2

• Adequate bone marrow function (Hb ≥ 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 ≤ 1.5 times upper limit of normal (ULN) (Patients with Gilbert'ssyndrome total bilirubin must be ≤4 times institutional upper limit of normal).

• Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≤ 3 times ULN (if related to liver metastases ≤ 5 times ULN)

• Ability to swallow medication

• Recovered from any previous therapy related toxicity to ≤ grade 1 at study entry (except for stable sensory neuropathy ≤ grade 2 and alopecia)

• Availability of archival tumor material for central review (if not please obtain anew tumor biopsy)

• Written signed informed consent

• Ability to adhere to the study visits and all protocol requirements

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 dayof study drug dosing

• History or presence of clinically relevant cardiovascular abnormalities such asuncontrolled 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 couldaffect 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 BDNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or knownHIV 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 doseof study drug

• Requiring treatment with any of the prohibited concomitant medications listed inSection 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-melanomaskin 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 withthe evaluation of the efficacy and safety of the test drug