A Trial of Endostar in Patients With Carcinoma of the Head and Neck
A Trial of Endostar in Patients With Carcinoma of the Head and Neck
The purpose of this study is to evaluate the efficacy and safety of recombinant human
 endostatin（continuously-pumped）combined with chemoradiotherapy in patients with advanced
 squamous cell carcinoma of the head and neck. The patients will be randomized to concurrent
 radiotherapy (CRT) arm and CRT + Endostar arm. All patients will receive one cycles of
 induction chemotherapy, intensity modulated radiation therapy (IMRT) with weekly cisplatin
 and 3 cycles of chemotherapy after IMRT. Treatment cycles will be repeated every 21 days for
 a maximum of 4 cycles. In CRT + Endostar arm, Endostar will be continuously intravenous
 pumped (7.5 mg/m2) for 14 days (d1-d14) during chemotherapy and for 5 days/week (d-5-d-1,
 d3-d7, d10-d14, d17-d21) during IMRT.
The patients will be randomized to CRT arm and CRT + Endostar arm. All patients will receive
 one cycles of induction chemotherapy, intensity modulated radiation therapy (IMRT) with
 weekly cisplatin and 3 cycles of chemotherapy after IMRT. Treatment cycles will be repeated
 every 21 days for a maximum of 4 cycles. In CRT + Endostar arm, Endostar will be continuously
 intravenous pumped (7.5 mg/m2) for 14 days (d1-d14) during chemotherapy and for 5 days/week
 (d-5-d-1, d3-d7, d10-d14, d17-d21) during IMRT.

 Prior to enrollment in this study and while the patient is receiving the therapy, routine
 tests, ECG, head and neck CT scan and MRI will be performed to check the body's response to
 the treatment. Further more, before and after the treatment, the circulating endothelial
 cells (CECs), endothelial progenitor cells (CEPs), vascular endothelial growth factor (VEGF),
 Cancer embryo antigen (CEA), Neuron-specific enolase (NSE) in blood and Microvessel density
 (MVD), hypoxia-inducible factor-1a (HIF-1a), P53, VEGF, Survivin in pathological specimens
 will be tested.

 Patients with progressive disease or intolerable side effects will be removed from the study.
 Patients with stable disease or tumor response will continue therapy for a maximum of 4
 cycles.

 Primary outcome: The response rate (RR), the clinical benefit rate (CBR), time of tumor
 progression (TTP).

 Secondary outcomes: The quality of life (QOL)，Safety and Tolerability.
Inclusion Criteria:

 -  Histologically confirmed unrespectable or postoperative recurrent squamous cell
 carcinoma of the head and neck;

 -  No prior radiation or chemotherapy and biotherapy before;

 -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.Life expectancy
 greater than 3 months;

 -  Patients must have adequate bone marrow function:

 -  Platelets ≥ 80×109/L

 -  Hemoglobin ≥100 g/L

 -  Absolute NeutrophilCount ≥1.5×109/L

 -  white blood cell≥ 3.5×109/L

 -  Patients must have adequate liver and renal function:

 -  Aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) < 2.5 × upper
 limit of normal

 -  Alkaline phosphatase < 2.5 × upper limit of normal

 -  Total bilirubin < 1.5 mg/dL

 -  Creatinine <1.5 mg/dL× upper limit of normal

 -  A cardiac ejection fraction > 50%;

 -  Ability to understand and willingness to sign a written informed consent.

 Exclusion Criteria:

 -  Participation in any investigational drug study within 4 weeks preceding the start of
 study treatment;

 -  Age ≤18 or ≥75 years of Age;

 -  Pregnant or breastfeeding women;

 -  Serious, uncontrolled, concurrent infection(s) requiring antibiotics;

 -  Clinically apparent central nervous system metastases or carcinomatous meningitis;

 -  Treatment for other carcinomas within the last 3 months;

 -  Patient unable or not willing to perform all study related biopsies and blood draws
 for exploratory endpoints will not be enrolled on study as all study related
 procedures are mandatory;

 -  Patients with clinically significant cardiac disease (New York Heart Association
 Classification III or IV and cardiac arrhythmias not well controlled with medication),
 or myocardial infarction within the previous six months.