Locally Advanced Nasopharyngeal Carcinoma
Conditions
Keywords
Concurrent Chemoradiotherapy
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.
Interventions
DRUGFamitinib
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.
DRUGCisplatin
100 mg/m2, D1, D22, and D43(q3w)
RADIATIONradiation（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
Sponsors
Sun Yat-sen University
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) | 3 weeks | To evaluate the DLT and MTD in patients with Concurrent Chemoradiotherapy With Famitinib |
Secondary
| Measure | Time frame |
|---|---|
| OS(Overall Survival) | 2 years and 3 years |
| DFMR(Distant Free Metastases Rate) | 2 years and 3 years |
| DFSR(Disease Free Survival Rate) | 2 years and 3 years |
| ORR (Objective Response Rate) | 12 weeks after treatment |
| 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 |
| To identify the tumor's molecular profiles in patients with NPCs | 2 years |
| To measure the changes of serum c-Kit，VEGF，Filt，KDR，and PDGFR | 2 years |
| LFRSR(Local Free Recurrence Survival Rate) | 2 years and 3 years |
Countries
China
Outcome results
None listed