Cetuximab for the Treatment of Advanced Unresectable or Metastatic Chordoma

Inclusion Criteria:

• Age ≥ 18 years

• Histologically confirmed diagnosis of chordoma which is advanced (unresectable)and/or metastatic

• ECOG Performance Status of ≤ 2

• At least one site of measurable disease on x-ray/CT/MRI and/or PET/CT scan asdefined by RECIST 1.1 criteria. Baseline imaging must be performed within 30 days ofDay 1 of study.

• Adequate organ function within 28 days of Day 1 of study defined as:

• The patient has adequate hematologic function, as evidenced by an absoluteneutrophil count (ANC) ≥ 1000/µL, hemoglobin ≥ 9 g/dL (5.58 mmol/L), and platelets ≥ 100,000/µL

• The patient has adequate hepatic function as defined by a total bilirubin ≤1.5 mg/dL (25.65 μmol/L) (NOTE: Patients with elevated bilirubin secondary to Gilbert'sdisease are eligible to participate in the study), and aspartate transaminase (AST)and alanine transaminase (ALT) ≤ 3.0 times the upper Page 26 limit of normal (ULN;or 5.0 times the ULN in the setting of liver metastases).

• The patient has adequate renal function as defined by a serum creatinine ≤1.5 timesthe ULN, or creatinine clearance (measured via 24-hour urine collection) ≥40mL/minute (that is, if serum creatinine is >1.5 times the ULN, a 24-hour urinecollection to calculate creatinine clearance must be performed). 3.1.6 Patients mayhave any prior line of therapy, but there should a washout period of at least 3weeks from any systemic therapy (small molecule/targeted agents, immunotherapies)and/or radiation therapy.

• Patients should be completely recovered from any reversible toxicities associatedwith any prior therapies.

• There should be access of archival tumor tissue for central pathology review, or anew tumor related biopsy should be considered within acceptable risk to the patient.

• Patients must have no prior history of use of an EGFR inhibitor for treatment oftheir chordoma

• Because the teratogenicity of cetuximab is not known, the patient, if sexuallyactive, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods. Women of childbearing potential include pre-menopausalwomen and women within the first 2 years of the onset of menopause. Women ofchildbearing potential must have a negative serum pregnancy test ≤ seven days priorto Day 1 of study.

• Life expectancy of > 3 months

Exclusion Criteria:

• Prior use of an EGFR inhibitor for treatment of their chordoma

• Non-metastatic, resectable disease

• No measurable disease according to RECIST 1.1

• Life expectancy of less than 3 months

• Other invasive malignancy within 2 years except for noninvasive malignancies such ascervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductalcarcinoma in situ of the breast that has/have been surgically cured.

• Concomitant participation to another clinical trial with active agent during thestudy (concomitant non-interventional study will be allowed) Page 27

• Patients who have a history of allergic reactions attributed to compounds ofchemical or biologic composition similar to those of cetuximab, red meat allergy, ortick bite history

• Patients with severe and/or uncontrolled concurrent medical disease that in theopinion of the investigator could cause unacceptable safety risks or compromisecompliance with the protocol

• The patient has clinically relevant coronary artery disease or history of myocardialinfarction in the last 12 months or high risk of uncontrolled arrhythmia oruncontrolled cardiac insufficiency.

• The patient has uncontrolled or poorly-controlled hypertension (>180 mmHg systolicor > 130 mmHg diastolic.

• Major surgery within 4 weeks prior to Day 1 of study or who have not recoveredadequately from prior surgery

• Patients who have received wide field radiotherapy ≤ 3 weeks or limited fieldradiation for palliation < 3 weeks prior to Day 1 of study or who have not recoveredadequately from side effects of such therapy

• Patients who have received any prior systemic therapy < 3 weeks prior to Day 1 ofstudy or have not recovered adequately from toxicities to the baseline.

• Women who are pregnant or nursing/breastfeeding.

• Inability to comply with protocol required procedures such as Medical, psychiatric,cognitive or other conditions that compromise the patient's ability to understandthe patient information, to give informed consent, to comply with the study protocolor to complete the study.