Clinical trial NCT03701451: Demethylated Drug in the Treatment of Nasopharyngeal Carcinoma
Official title: Clinical Efficacy Observation of Demethylated Drug Decitabine in the Treatment of Locally Advanced Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Nasopharyngeal Carcinoma
Keywords: Nasopharyngeal Carcinoma
Decitabine
Concurrent chemoradiotherapy
Induced chemotherapy
Lead sponsor: Guilin Medical University, China
Sponsor class: OTHER
Collaborators: name: Guilin Hospital of Traditional Chinese Medicine
First posted: 2018-10-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study is to observe the efficacy and toxicity of demethylating drug decitabine and cisplatin induced chemotherapy for 3 cycles followed by concurrent chemoradiotherapy in the treatment of regionally advanced nasopharyngeal carcinoma,followed up for 2 years, observing the 2-year survival rate and variation of degrees of methylation before and after treatment,providing clinical basis for the clinical study of stage II-III.

Detailed description: Recent studies and previous studies in the investigator's research group have found that nasopharyngeal carcinoma is a disease with hypermethylation changes, and epigenetic treatment has not yet been carried out in nasopharyngeal carcinoma. In this study, Simon's two-stage design method was used to select 30 patients with nasopharyngeal carcinoma, treated with demethylating drug decitabine 7mg/m2 d1-5 + cisplatin 80mg/m2 d1 induced chemotherapy for 3 cycles followed by concurrent chemoradiotherapy with cisplatin 80mg/m2. observing the efficacy and toxicity of decitabine in the treatment of regionally advanced nasopharyngeal carcinoma, followed up for 2 years, observing the 2-year survival rate,evluating the relationship between different degrees of methylation and survival before and after treatment,provide clinical basis for the clinical study of stage II-III.

Eligibility criteria: Inclusion Criteria:

1. Patients with newly confirmed non-keratinized or undifferentiated carcinoma of the nasopharynx.
2. Aequate hematological function: WBC ≥ 4 × 10\^9 / L before the enrollment, PLT ≥ 100 × 10\^9 / L, HGB ≥ 80.0g / L.
3. Adequete liver function:(serum transminase ≤ 2.5 times higher than upper limit ), renal function:(creatinine clearance rate ≥ 60 ml / min).
4. Karnofsky performance status(KPS) score of at least 70 or Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Patients must give signed infomed consent.

Exclusion Criteria:

1. Other or mixed pathological type.
2. age \>65years.
3. severe heart,liver,and kidney damage.
4. histology of other malignancy .
5. prior chemotherapy or radiation of the primary tumor;Pregnant or lactating women.
6. History of psychiatric disorders .
7. Positive urine protein.
8. A healed wound for long time or incomplete fracture.
9. Before treatment,MRI showed that the tumor might be an important risk factor (for example, wrapping around the internal carotid artery / vein); or researchers judged that the tumor is a high risk of serious blood vessel bleeding during the treatment.
10. Patient who has high blood pressure can not be controlled by a single antihypertensive drug treatment (Systolic pressure \> 140 mmHg, diastolic pressure \> 90 mmHg.
11. Any unstable angina pectoris;with a history of angina pectoris were newly diagnosed with angina pectoris within 3 months before screening; any myocardial infarction events occurred within 6 months before screening; arrhythmia (including QTcF: male ≥ 450ms, female ≥ 470 ms) need long time use of antiarrhythmic drugs and heart function insufficiency ≥II according to New York Heart Association class.
12. Medical history of arteriovenous thrombosis event within the past year, such as cerebral vascular accident (including transient ischemic attack) and deep venous thrombosis (venous catheter thrombosis caused by chemotherapy and investigator judged that the patient had recovered, these patients should be except) and pulmonary embolism.
13. Patient who has serious hemorrhages, any serious bleeding events classification at 3 degree or more (according to CTCAE4.0) within the last 4 weeks.
14. Patient who has abnormal coagulation and bleeding tendency (signed informed consent before 14 days, and must be satisfied: INR is in the normal range without the use of anticoagulants); Application of anticoagulants or vitamin K antagonists such as Hua Falin, heparin or its analogues, with international normalized ratio (INR) is less than 1.5, allows the use of small dose Hua Falin (1 mg orally, once daily) or small dose aspirin (total dose ≤ 100 mg daily).
15. For females:patients should be surgical sterilization or postmenopausal patients, or willing to receive a medical approved contraception during treatment and 6 months after the end of the treatment; serum or urine pregnancy test must be negative, and must be non lactating period within 7 days before study; for males: patients should be treated with surgical sterilization or willing to receive a medical approved contraception during treatment and 6 months after the end of the treatment.
16. Any factors that affect the oral drug, such as the inability to swallow, diarrhea and intestinal obstruction.
17. Medical history of immunodeficiency, or other acquired, congenital immunodeficiency disease, or history of organ transplantation.
18. Any serious harm to the subject's safety or 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: Progression-free survival
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival
timeFrame: 2 years
measure: Locoregional recurrence-free survival
timeFrame: 2 years
measure: Distant metastasis-free survival
timeFrame: 2 years
measure: Dgree of methylation Carcinoma
timeFrame: 2 months
measure: Treatment toxicity
timeFrame: 2moths to 2 years
Other outcomes:
Locations:
city: Guilin
country: China
facility: Guilin Hospital of Traditional Chinese Medicine
state: Guangxi
city: Guilin
country: China
facility: Guilin Medical University
state: Guangxi
Study officials:
affiliation: Guilin Medical University, China
name: Wei Jiang, PhD
role: STUDY_DIRECTOR
References: