FMTN-I-LNPC: Concurrent Chemoradiotherapy With Famitinib for Patients With Locally Advanced Nasopharyngeal Carcinoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Drug: Famitinib
|
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.
Drug: 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
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- ORR (Objective Response Rate) [12 weeks after treatment]
- 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]
- LFRSR(Local Free Recurrence Survival Rate) [2 years and 3 years]
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically confirmed nasopharyngeal differentiation or undifferentiation carcinoma, WHO II or III
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Newly diagnosed T3-4N1（exception metastatic uni or bil retropharyngeal lymph nodes N1） or any TN2-3(7th UICC/AJCC) locally advanced nasopharyngeal carcinoma
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18-65 years of age
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ECOG performance status of 0 or 1
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Life expectancy of more than 6 months
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At least one measurable lesion :MRI scan larger than 10 mm in diameter, malignant lymph nodes larger than 10 mm in short axis
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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.
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Signed and dated informed consent. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.
Exclusion Criteria:
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Before or at the same time any second malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
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Any factors that influence the usage of oral administration
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Known Spinal Cord compression or diseases of brain or pia mater by CT /MRI Screening
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Imageology shows that tumor lesion less than 5 mm to great vessels(internal carotid and jugular vein)
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Hemoglobin < 90g/L, platelets < 100×109/L, neutrophils < 2×109/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
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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
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URT: urine protein ≥ ++ and > 1.0 g of 24 h
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Long-term untreated wounds or fractures
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PT, APTT, TT, Fbg abnormal, having hemorrhagic tendency (eg. active peptic ulcer disease) or receiving the therapy of thrombolysis or anticoagulation
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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
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Preexisting thyroid dysfunction, even using medical therapy, thyroid function cannot maintain in the normal range
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Abuse of Psychiatric drugs or dysphrenia
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Subject of Viral hepatitis type B or type C
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Subject of immunodeficiency: HIV positive, or other acquired immunodeficiency, congenital immunodeficiency, or organ transplantation
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With drug CYP3A4 inhibitor, inducer, or substrate
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Medical Oncology, Cancer Center, Sun Yet-sen University | Guangzhou | Guangdong | China |
Sponsors and Collaborators
- Jiangsu HengRui Medicine Co., Ltd.
- Sun Yat-sen University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- FMTN-I-LNPC