Apatinib for Advanced Non-squamous Head and Neck Cancer
Apatinib for Advanced Non-squamous Head and Neck Cancer
In this study, the investigators try to evaluate the efficacy and safety of apatinib in
 advanced non-squamous head and neck cancer and to validate the correlative biomarkers.
There is no standard therapy for patients with advanced (unresectable, locally advanced,
 recurrent or metastatic) non-squamous head and neck cancer. Apatinib is a novel vascular
 endothelial growth factor receptor 2 tyrosine kinase inhibitor, which has been approved for
 the treatment of patients with advanced gastric cancer refractory to two or more lines of
 prior chemotherapy. Vascular endothelial growth factor is highly expressed in non-squamous
 head and neck cancer and its expression correlates with stage, tumour size, vascular
 invasion, recurrence and metastasis. In this study, the investigators try to evaluate the
 efficacy and safety of apatinib in advanced non-squamous head and neck cancer and to validate
 the correlative biomarkers.
Inclusion Criteria:

 -  18 years to 75 years;

 -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2;

 -  Life expectancy of more than 12 weeks;

 -  At least one measurable lesion according to RECIST 1.1 which has not received
 radiotherapy =< 3 months;

 -  Histologically confirmed advanced (unresectable, locally advanced, recurrent or
 metastatic) non-squamous head and neck cancer, including adenocarcinoma,
 mucoepidermoid carcinoma, acinar cell carcinoma and adenoid cystic carcinoma;

 -  Recurrent and or metastatic lesions which are not suitable for local treatment;

 -  For patients with mucoepidermoid carcinoma, acinar cell carcinoma or adenoid cystic
 carcinoma, metastatic disease documented as having shown progression on a scan (CT,
 MRI) compared to a previous scan taken at any time in the past 12 months;

 -  For patients with adenocarcinoma, one regimen of prior chemotherapy was received for
 recurrent and or metastatic diseases;

 -  Adequate hepatic, renal, heart, and hematologic functions: absolute neutrophil count
 (ANC) ≥ 1.5×109/L, platelet count (PLT) ≥ 100×109/L, hemoglobin (HB) ≥ 90 g/L, total
 bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN), alternate aminotransferase (ALT)
 or aspartate aminotransferase (AST) ≤ 2.5×ULN (or ≤ 5×ULN in patients with liver
 metastases), Serum Cr ≤ 1×ULN, Cr clearance ≥ 50 mL/min, international normalized
 ratio (INR) < 1.5 or PT < ULN+4s or activated partial thromboplastin time (APTT) <
 1.5×ULN, proteinuria < (++) or urinary protein ≤ 1.0 g/24 hrs;

 -  For women of child-bearing age, the pregnancy test results (serum or urine) within 7
 days before enrolment must be negative. They will take appropriate methods for
 contraception during the study until the 8th week post the last administration of
 study drug. For men (previous surgical sterilization accepted), will take appropriate
 methods for contraception during the study until the 8th week post the last
 administration of study drug.

 -  Signed informed consent.

 Exclusion Criteria:

 -  Accumulation of coelomic fluid (e.g. pleural effusion, ascites fluid, cardiac
 effusion) requiring treatment;

 -  Other malignancy within the past five years other than basal cell skin cancer, or
 carcinoma in situ of the cervix;

 -  Factors affecting the oral medication (e.g. inability to swallow, chronic diarrhea and
 intestinal obstruction);

 -  Major injuries and/or surgery =< 4 weeks prior to registration with incomplete wound
 healing. Patients who have received radiotherapy (except local palliative
 radiotherapy), chemotherapy, molecular targeted therapy =< 3 weeks, or
 nitrosoureas/mitomycin chemotherapy =< 6 weeks prior to registration;

 -  Patients with poor-controlled arterial hypertension (systolic pressure ≥ 140 mmHg
 and/or diastolic pressure ≥ 90 mm Hg) despite standard medical management;

 -  Suffered from grade II or above myocardial ischemia or myocardial infarction,
 uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female ≥ 470 ms). Grade
 III-IV cardiac insufficiency according to New York Heart Association (NYHA) criteria
 or echocardiography check: left ventricular ejection fraction (LVEF)<50%;

 -  History of clinically significant haemoptysis =< 2 months (more than half of one tea
 spoon of fresh blood per day) prior to registration. Coagulation disfunction,
 hemorrhagic tendency or receiving anticoagulant therapy;

 -  History of clinically relevant major bleeding event (e.g. gastrointestinal hemorrhage,
 bleeding ulcer, occult blood ≥ (++), and vasculitis) =< 3 months prior to
 randomization;

 -  Patients who have active brain metastases or leptomeningeal disease. Patients with
 treated brain metastases are eligible if they are clinically stable with regard to
 neurologic function, off steroids after cranial irradiation ending at least 3 weeks
 prior to randomization, or after surgical resection performed at least 3 weeks prior
 to randomization. No evidence of Grade greater than or equal to 1 central nervous
 system (CNS) hemorrhage based on pretreatment CT or MRI scan;

 -  Centrally located tumors of local invasion of major blood vessels, or distinct
 interstitial lung disease by the chest radiographic findings (CT or MRI);

 -  Treatment with other investigational drugs or other anti-cancer therapy;

 -  Previous therapy with other VEGFR inhibitors (other than bevacizumab);

 -  Treatment in another investigational trial =< 4 weeks prior to registration;

 -  History of hypersensitivity to apatinib and/or the excipients of the trial drugs;

 -  Active or chronic hepatitis C and/or B infection, or other active uncontrolled
 infection;

 -  History of immunodeficiency disease (including HIV positive), concurrent acquired or
 congenital immunodeficiency syndrome, or history of organ transplantation;

 -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
 =< 6 months prior to registration;

 -  History of arterial or venous thromboembolic events (e.g. cerebrovascular accident,
 cardiovascular accident, deep venous thrombosis and pulmonary embolism) =< 12 months
 prior to randomization;

 -  Administration of strong/potent cytochrome P450 (CYP)3A4 inhibitors within 7 days, or
 inducers within 12 days;

 -  Evidence of significant medical illness that in the investigator's judgment will
 substantially increase the risk associated with the subject's participation in and
 completion of the study;

 -  History of mental diseases;

 -  Other conditions regimented at investigators' discretion.