The Clinical Study of Apatinib Plus S1 for Patients With Advanced Non-squamous Head and Neck Cancer

Head and Neck Neoplasms Clinical Trial

Official title:

PhaseⅡSingle-center, Open-label, Exploratory Clinical Study of Apatinib in Combination With S1 for the Patients With Advanced Non-squamous Head and Neck Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02943252
• Other study ID #: CH-H&N-008
• Status: Recruiting
• Phase: Phase 2
• First received: October 19, 2016
• Last updated: October 21, 2016
• Start date: October 2016
• Est. completion date: October 2021

Study information

• Verified date: October 2016
• Source: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Contact: Xiaohui He, B.D.
• Phone: +86-13810670129
• Email: xiaohuih2008[@]163.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a Single-center, Open-label, Single-arm, Phase Ⅱ exploratory clinical trial evaluating the efficacy and safety of Apatinib plus S1 for patients with advanced (unresectable, locally advanced, recurrent or metastatic) non-squamous head and neck cancer.

Description:

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. S1 is a new kind of oral fluorouracil antineoplastic chemotherapy drugs. In vitro, apatinib has synergy effect with fluorouracil. In this study, the investigators try to evaluate the efficacy and safety of apatinib and S1 in advanced non-squamous head and neck cancer and to validate the correlative biomarkers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 2021
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Head and Neck Neoplasms

Intervention

Drug:
• Apatinib
apatinib 500 mg in tablet once daily
• S1
S-1 40-60mg bid, days 1-14 , every 3 weeks

Locations

Country	Name	City	State
China	Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC)	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Country where clinical trial is conducted

China, 

References & Publications (3)

Le Tourneau C, Razak AR, Levy C, Calugaru V, Galatoire O, Dendale R, Desjardins L, Gan HK. Role of chemotherapy and molecularly targeted agents in the treatment of adenoid cystic carcinoma of the lacrimal gland. Br J Ophthalmol. 2011 Nov;95(11):1483-9. do — View Citation

Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. R — View Citation

Yamashita T, Shinden S, Watabe T, Shiotani A. Outpatient chemotherapy with S-1 for recurrent head and neck cancer. Anticancer Res. 2009 Feb;29(2):577-81. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	serum soluble VEGFR2		baseline	No
Other	tumor phosphorylated VEGFR2 (p-VEGFR2) expressions		baseline	No
Primary	Response Rate		up to 3 years	No
Secondary	Progression-free survival		up to 3 years	No
Secondary	Overall survival		up to 3 years	No
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0		up to 3 years	Yes