Concurrent Chemoradiotherapy With Famitinib for Patients With Locally Advanced Nasopharyngeal Carcinoma

Locally Advanced Nasopharyngeal Carcinoma Clinical Trial

— FMTN-I-LNPC  

Official title:

Phase I Study of Concurrent Chemoradiotherapy With Famitinib for Patients With Locally Advanced Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01462474
• Other study ID #: FMTN-I-LNPC
• Status: Completed
• Phase: Phase 1
• First received: October 27, 2011
• Last updated: April 16, 2018
• Start date: October 2011
• Est. completion date: January 2016

Study information

• Verified date: November 2011
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Famitinib is a tyrosin-inhibitor agent targeting at c-Kit, VEGFR2, PDGFR, VEGFR3, Flt1 and Flt3. Phase I study of mono famitinib has shown that the drug's toxicity is manageable.

PURPOSE: This phase I trial is studying the safety and tolerance of concurrent chemoradiotherapy with famitinib for patients with locally advanced nasopharyngeal carcinoma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 2016
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Histologically confirmed nasopharyngeal differentiation or undifferentiation carcinoma, WHO II or III

• Newly diagnosed T3-4N1(exception metastatic uni or bil retropharyngeal lymph nodes N1) or any TN2-3(7th UICC/AJCC) locally advanced nasopharyngeal carcinoma

• 18-65 years of age

• ECOG performance status of 0 or 1

• Life expectancy of more than 6 months

• At least one measurable lesion :MRI scan larger than 10 mm in diameter, malignant lymph nodes larger than 10 mm in short axis

• Female: All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 6 months after the last dose of test article. Child bearing potential, a negative urine or serum pregnancy test result before initiating Famitinib. Male: All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 6 months after the last dose of test article.

• Signed and dated informed consent. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.

Exclusion Criteria:

• Before or at the same time any second malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix

• Any factors that influence the usage of oral administration

• Known Spinal Cord compression or diseases of brain or pia mater by CT /MRI Screening

• Imageology shows that tumor lesion less than 5 mm to great vessels(internal carotid and jugular vein)

• Hemoglobin < 90g/L, platelets < 100×10^9/L, neutrophils < 2×10^9/L, total bilirubin = 1.25×the upper limit of normal(ULN), ALT\AST = 1.5x ULN), serum creatine > 1x ULN, creatinine clearance rate < 60ml/min, Cholesterol > 7.75 mmol/L and triglyceride > 3 mmol/L, LVEF: < LLN

• Hypertensive( more than 140/90 mmHg ), more than class I (NCI CTCAE 3.0 ) myocardial ischemia, arrhythmia(including QTcF:male = 450 ms, female =470 ms), or cardiac insufficiency

• URT: urine protein = ++ and > 1.0 g of 24 h

• Long-term untreated wounds or fractures

• PT, APTT, TT, Fbg abnormal, having hemorrhagic tendency (eg. active peptic ulcer disease) or receiving the therapy of thrombolysis or anticoagulation

• Before the first treatment occurs artery / venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism, etc

• Preexisting thyroid dysfunction, even using medical therapy, thyroid function cannot maintain in the normal range

• Abuse of Psychiatric drugs or dysphrenia

• Subject of Viral hepatitis type B or type C

• Subject of immunodeficiency: HIV positive, or other acquired immunodeficiency, congenital immunodeficiency, or organ transplantation

• With drug CYP3A4 inhibitor, inducer, or substrate

• 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

Related Conditions & MeSH terms

• Carcinoma
• Locally Advanced Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• Famitinib
Either at 12.5 mg, 16.5 mg?20 mg or 25 mg qd p.o., 2 weeks before concurrent chemoradiotherapy and D1-D49, exception D1, D22, and D43.
• Cisplatin
100 mg/m2, D1, D22, and D43(q3w)

Radiation:
• radiation(IMRT)
IMRT (Intensity-Modulated Radiation Therapy). Radiation is delivered to GTV at 70 Gy in 32-33 fractions, CTV1 at 60 Gy in 32-33 fractions and CTV2 at 54 Gy in 32-33 fractions

Locations

Country	Name	City	State
China	Department of Medical Oncology, Cancer Center, Sun Yet-sen University	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.	Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD)	To evaluate the DLT and MTD in patients with Concurrent Chemoradiotherapy With Famitinib	3 weeks
Secondary	ORR (Objective Response Rate)		12 weeks after treatment
Secondary	OS(Overall Survival)		2 years and 3 years
Secondary	DFMR(Distant Free Metastases Rate)		2 years and 3 years
Secondary	DFSR(Disease Free Survival Rate)		2 years and 3 years
Secondary	LFRSR(Local Free Recurrence Survival Rate)		2 years and 3 years
Secondary	Quantitative evaluation of the blood perfusion of the metastatic cervical lymph nodes by dynamic contrast-enhanced ultrasonography after a loading dose of famitinib for 14 days		2 weeks
Secondary	To identify the tumor's molecular profiles in patients with NPCs		2 years
Secondary	To measure the changes of serum c-Kit,VEGF,Filt,KDR,and PDGFR		2 years