Clinical trial NCT01462474: Concurrent Chemoradiotherapy With Famitinib for Patients With Locally Advanced Nasopharyngeal Carcinoma
Official title: Phase I Study of Concurrent Chemoradiotherapy With Famitinib for Patients With Locally Advanced Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced Nasopharyngeal Carcinoma
Keywords: Concurrent Chemoradiotherapy
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Sun Yat-sen University
First posted: 2011-10-31
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD)
timeFrame: 3 weeks
Secondary outcomes:
measure: ORR (Objective Response Rate)
timeFrame: 12 weeks after treatment
measure: OS(Overall Survival)
timeFrame: 2 years and 3 years
measure: DFMR(Distant Free Metastases Rate)
timeFrame: 2 years and 3 years
measure: DFSR(Disease Free Survival Rate)
timeFrame: 2 years and 3 years
measure: LFRSR(Local Free Recurrence Survival Rate)
timeFrame: 2 years and 3 years
measure: 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
timeFrame: 2 weeks
measure: To identify the tumor's molecular profiles in patients with NPCs
timeFrame: 2 years
measure: To measure the changes of serum c-Kit，VEGF，Filt，KDR，and PDGFR
timeFrame: 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Medical Oncology, Cancer Center, Sun Yet-sen University
state: Guangdong
Study officials:
References: