Famitinib in Treating Patients With Recurrent and/or Metastatic Nasopharyngeal Carcinoma (NPC)

Study Overview
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Brief Summary
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RATIONALE: Famitinib is a tyrosin-inhibitor agent targeting at c-Kit, VEGFR2, PDGFR, VEGFR3, Flt1 and Flt3. Phase I study has shown that the drug's toxicity is manageable. PURPOSE: This phase II trial is studying how well famitinib works in treating patients with recurrent and/or metastatic NPC.

Official Title
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A Single-arm, Open, Multicenter, Phase II Study of Famitinib as ≥Third Line Treatment in Patients With Recurrent and/or Metastatic Nasopharyngeal Carcinoma (NPC)

Conditions
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Recurrent Nasopharyngeal Carcinoma, Metastatic Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Famitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologic confirmed recurrent and/or metastatic nasopharyngeal carcinoma( NPC ) Have failed for ≥2 lines of chemotherapy At least one measurable lesion, larger than 10 mm in diameter by spiral CT scan(scanning layer ≤ 5 mm ) ≥ 18 and ≤ 70 years of age ECOG performance scale 0-2 Life expectancy of more than 3 months More than 4 weeks after operation, chemotherapy, radiotherapy, cytotoxic agents or tyrosine kinase inhibitors Adequate hepatic, renal, heart, and hematologic functions (hemoglobin ≥ 90g/L, platelets ≥ 80×10^9/L, neutrophils ≥ 1.5×10^9/L, 24-hour urinary protein ≤ 1.0 g total bilirubin < 1.25×the upper limit of normal(ULN), and serum transaminase < 1.5×the ULN (If liver metastases, serum transaminase< 2.5×the ULN), serum creatine ≤ 1x ULN, creatinine clearance rate > 50ml/min, Cholesterol≤7.75 mmol/L and triglyceride≤2.5 x ULN, LVEF: ≥ 50% Patients could provide 4-6 pieces of organization wax or pathological section 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: Prior therapy with tyrosine kinase -inhibitor agent targeting at VEGFR, PDGFR and c-Kit Prior radiotherapy more than 2 courses Before or at the same time any, second malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix Less than 4 weeks from the last clinical trial 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 Preexisting uncontrolled hypertension defined as more than 140/90 mmHg despite using single medical therapy, more than cla ss I (NCI CTCAE 3.0 ) myocardial ischemia, arrhythmia, or cardiac insufficiency URT: urine protein ≥ ++ and > 1.0 g of 24 h Long-term untreated wounds or fractures Blood coagulation abnormal, having hemorrhagic tendency (eg. active peptic ulcer disease) or receiving the therapy of thrombolysis or anticoagulation. Within 6 months before the first treatment occurrs artery / venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism, etc. Application of anticoagulants or vitamin K antagonists such as warfarin, heparin or its analogues; If the prothrombin time international normalized ratio (INR) ≤ 1.5, with the purpose of prevention, the use of small doses of warfarin (1mg orally, once daily) or low-dose aspirin (between 80mg to 100mg daily) is allowed Preexisting thyroid dysfunction, even using medical therapy, thyroid function cannot maintain in the normal range Abuse of Psychiatric drugs or dysphrenia Viral hepatitis type B or type C Immunodeficiency: HIV positive, or other acquired immunodeficiency, congenital immunodeficiency, or organ transplantation 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug: Famitinib<br> | Drug: Famitinib<br>* 25 mg qd p.o. and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CBR(Clinical Benefit Rate) | To evaluate the efficacy (clinical benefit rate) of single-agent famitinib in patients with recurrent or metastatic NPC | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR (Objective Response Rate) |  | 12 weeks | 
| PFS(Progress Free Survival) |  | 3 years | 
| DCR(Disease Control Rate) |  | 12 weeks | 
| OS(Sverall Survival) |  | 3 years | 
| To evaluate the safety and tolerability | Number of participants with adverse events and serious adverse events.In addition,estimating their relationship with Famitinib. | 3 years | 
| QoL(Quality of Life) |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent and/or Metastatic Nasopharyngeal Carcinoma (NPC)